LUPRON
leuprolide acetate
Physician's Desk Reference (PDR)

leuprolide acetate (Lupron)- Drug Summary

Cytostatic Gonadotropin-Releasing Hormone Agonists
Gonadotropin-Releasing Hormone Agonists

DESCRIPTION

Synthetic nonpeptide analog of gonadotropin-releasing hormone (GnRH)
Used for endometriosis, precocious puberty, prostate cancer, and uterine fibroids
May cause an increase in symptoms during the first weeks of therapy; monitor patients closely

Eligard/Fensolv Subcutaneous Inj Susp: 7.5mg, 22.5mg, 30mg, 45mg
Leuprolide Acetate/Lupron Subcutaneous Inj Sol: 0.2mL, 1mg
Lupron Depot/Lupron Depot-Ped Intramuscular Inj Pwd F/Susp: 3.75mg, 7.5mg, 11.25mg, 15mg, 22.5mg, 30mg, 45mg

42 mg subcutaneously once every 6 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. After the first injection of leuprolide mesylate, serum testosterone concentrations were suppressed to 50 ng/dL or less by week 4 in 98.5% of patients with advanced prostate cancer and a baseline serum testosterone concentration greater than 150 ng/dL in a multinational, single-arm study; serum testosterone was 50 ng/dL or less from week 4 to week 48 in 97% of patients. Serum testosterone concentrations were 20 ng/dL or less on day 28 in 69.3% of patients.

Subcutaneous dosage (leuprolide acetate for injection [Lupron and generic equivalents])

1 mg subcutaneously once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a controlled study, the survival rate for leuprolide acetate 1 mg subcutaneously once daily was comparable to diethylstilbestrol (DES) 3 mg daily in patients with advanced prostate cancer after 2 years of treatment; the objective response to treatment was also similar for the 2 groups.

Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 1-Month])

7.5 mg subcutaneously once monthly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 21.8 ng/dL; 94.1% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 42. There were no breakthrough occurrences of testosterone concentration greater than 50 ng/dL at any time point after testosterone suppression was achieved.

Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 3-Month])

22.5 mg subcutaneously every 3 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 21 after treatment with every3-month subcutaneous leuprolide acetate was 27.7 ng/dL; 99% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 35. Once testosterone suppression was achieved, one patient (less than 1%) demonstrated breakthrough (testosterone concentration greater than 50 ng/dL) following the initial injection; that patient remained below the castrate threshold following the second injection.

Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 4-Month])

30 mg subcutaneously every 4 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 17.2 ng/dL; 96% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28 and 100% were below the castrate threshold at day 42. Three patients (3%) demonstrated breakthrough testosterone concentrations (greater than 50 ng/dL) after the second injection once testosterone suppression was achieved; castrate suppression was reached again up to 18 days after the second injection and was maintained thereafter in all 3 patients.

Subcutaneous dosage (leuprolide acetate for injectable suspension [Eligard 6-Month])

45 mg subcutaneously every 6 months. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, open-label study, the mean testosterone concentration on day 28 after treatment with once-monthly subcutaneous leuprolide acetate was 16.7 ng/dL; 99.1% of patients had testosterone concentrations below the castrate threshold (50 ng/dL) at day 28. One patient (less than 1%) demonstrated a breakthrough testosterone concentration (greater than 50 ng/dL) once testosterone suppression was achieved. This patient reached castrate suppression at day 21 and remained suppressed until day 308 (testosterone concentration, 112 ng/dL); at day 336, his testosterone concentration was 210 ng/dL.

Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 1-Month])

7.5 mg IM every 4 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with previously untreated stage D2 prostate cancer received leuprolide as a once-monthly IM depot injection. Serum testosterone increased by 50% or more above baseline during the first week of treatment in the majority of patients; it was suppressed to castrate levels within 30 days in 94% of patients and within 66 days in all patients. One patient had a breakthrough testosterone concentration (greater than 50 ng/dL) that was associated with a substantial dosing delay.

Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 3-Month])

22.5 mg IM every 12 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In clinical studies, serum testosterone was suppressed to castrate levels within 30 days in 95% of patients; one patient later experienced a transient minimal elevation of testosterone. During the initial 24 weeks of treatment, 85% of patients did not progress.

Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 4-Month])

30 mg IM every 16 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with previously untreated stage D2 prostate cancer were treated with leuprolide 30 mg IM every 4 months. Serum testosterone increased by 50% or more above baseline during the first week of treatment in the majority of patients; it was suppressed to castrate levels within 30 days in 94% of patients and within 43 days in all patients. Two patients had breakthrough testosterone concentrations (greater than 50 ng/dL) at week 16 and 17, respectively, which returned to castrate level by week 18.

Intramuscular dosage (leuprolide acetate for depot suspension [Lupron Depot 6-Month])

45 mg IM every 24 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, noncomparative trial, patients with prostate cancer were treated with leuprolide 45 mg IM every 24 weeks. Serum testosterone was suppressed to castrate levels (less than 50 ng/dL) from week 4 through week 48 in 93.4% of patients; 8 patients had breakthrough testosterone concentrations (greater than 50 ng/dL).

For the management of endometriosis including pain relief and reduction of endometriotic lesions.

Initially, 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months, given with or without norethindrone acetate 5 mg/day PO for a therapy duration of 6 months. For recurrence of symptoms, leuprolide must be given with norethindrone acetate 5 mg/day PO for 6 months; the total duration of therapy with leuprolide plus norethindrone acetate should not exceed 12 months. Assessment of bone density is recommended before retreatment. Clinical guidelines/studies suggest the addition of hormonal add-back therapy (e.g., estrogens and/or progestins) is effective at reducing the bone mineral loss which occurs with leuprolide therapy alone. Such therapy does not compromise the efficacy of leuprolide in relieving endometriosis symptoms and may also reduce vasomotor symptoms and vaginal dryness associated with hypoestrogenism.

For the treatment of central precocious puberty (idiopathic or neurogenic) in children.
NOTE: Leuprolide has been designated an orphan drug by the FDA for this indication.
NOTE: Downregulation is determined by GnRH agonist stimulation test, sex steroid concentrations, and Tanner staging. Give consideration to discontinuing treatment before 11 years of age in girls and 12 years of age in boys.

NOTE: Do not use partial syringes or a combination of syringes to achieve a particular dose or to titrate dosages. Each 1-month depot syringe dose strength and formulation has different release characteristics.

The recommended dose is 15 mg IM as a single dose repeated every 4 weeks. In clinical trials, patients receiving this dosage ranged from 39.3 to 57.5 kg body weight. May adjust dose if changes in body weight occur. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

The recommended dose is 11.25 mg IM as a single dose repeated every 4 weeks. Increase dose if needed to the next available higher dose (e.g., 15 mg) at next monthly injection until total down-regulation is achieved. May adjust dose if changes in body weight occur. In clinical trials, patients receiving the 11.25 mg dosage ranged from 28.4 to 36.8 kg body weight. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

The recommended dose is 7.5 mg IM as a single dose repeated every 4 weeks. Increase dose if needed to the next available higher dose (e.g., 11.25 or 15 mg) at next monthly injection until total down-regulation is achieved. May adjust dose if changes in body weight occur. In clinical trials, patients receiving the 7.5 mg dosage ranged from 20.2 to 27 kg body weight. Monitor hormonal and clinical parameters at month 1 to 2, with dose changes, and further as appropriate to ensure adequate suppression.

Once every 3 months regimen.
NOTE: Do not use partial syringes or a combination of syringes to achieve a particular dose or to titrate dosages. Each 3-month depot syringe dose strength and formulation has different release characteristics.

11.25 mg or 30 mg IM as a single dose repeated every 12 weeks (3 months). In order to ensure adequate suppression, monitor hormonal and clinical parameters at month 2 to 3, month 6, and further as judged clinically appropriate; in the case of inadequate suppression, consider other available GnRH agonists indicated for the treatment of central precocious puberty.

50 mcg/kg/dose subcutaneous once daily. If response is not satisfactory, dosage may be titrated upward in 10 mcg/kg/day increments.[45475]

For the preoperative treatment of anemia due to uterine leiomyomata (fibroids) in combination with iron supplementation when iron therapy alone fails to correct the anemia.

3.75 mg IM once monthly or 11.25 mg IM every 3 months in combination with supplemental iron therapy. The recommended duration of therapy is 3 months or less. Only use the 3-month depot dosage when 3 months of hormonal suppression is deemed necessary. Retreatment depends on the return of symptoms. LIMITATIONS OF USE: Leuprolide 3-month Depot 11.25 mg is not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids. Do not substitute leuprolide depot 11.25 mg for leuprolide depot 3.75 mg.

In several trials, 1 mg subcutaneous once daily has been used. Because the condition is reversible if the drug is discontinued, therapy must be continuous.

A long-acting, depot formulation administered in a dosage of 3.75 mg IM once every 28 days for 24 weeks was effective. Because the condition is reversible if the drug is discontinued, therapy must be continuous.

For the adjuvant treatment of premenopausal women with hormone receptor-positive breast cancer†.

11.25 mg subcutaneous once every 3 months for 2 years has been studied. In a study of 589 patients, leuprolide as compared to 6 cycles of CMF chemotherapy (cyclophosphamide/methotrexate/5-fluorouracil) was shown to be non-inferior for 2-year relapse free survival (63.9% vs. 63.4%, p = 0.83). An exploratory survival analysis favored leuprolide at 5 years (HR 1.5, 95% CI 1.13 to 1.99, p = 0.005).

For the treatment of nonspecific symptoms associated with premenstrual syndrome (PMS)†.

0.5 to 1 mg subcutaneous once daily has been shown to decrease symptoms associated with PMS. Because of the adverse reaction profile (e.g., osteoporosis, premature coronary artery disease), leuprolide is generally considered a third line agent in the treatment of PMS.

For inhibiting premature leuteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation and subsequent in vitro fertilization (IVF) or other assisted reproductive technology (ART) for the treatment of infertility†.

Subcutaneous dosage for 'long-protocol' (leuprolide acetate injection solution only, do NOT use depot formulations)

Optimal daily dosage is individualized by the ART specialist; 'long-protocols' are most common but an alternative leuprolide 'flare protocol' is also used (not discussed here, such dosage regimens for flare protocols are much different than those of long protocols). In the long protocol, leuprolide is typically started on day 22 or 23 of the menstrual cycle prior to the ovarian stimulation cycle; dosages vary with usual range 0.5 to 1 mg per day subcutaneously. Women will menstruate, continuing to use the leuprolide during oocyte stimulation with FSH, which usually begins after estradiol suppression is documented. By day 3 of the menstrual cycle, the dosage of leuprolide is typically decreased by 50%. Leuprolide and FSH are administered until sufficient follicular development is attained. HCG is then administered to induce final follicular maturation for oocyte retrieval. FDA-approved medicines like ganirelix and cetrorelix are now more commonly used for this purpose.

Case reports suggest standard monthly injections of 1.3 to 7.5 mg IM are effective. An 18-year old male with sickle cell anemia received 5.25 mg IM once monthly for 2 months, followed by 2.625 mg IM monthly for 6 months and then 1.3 mg IM monthly for 8 months; priapism did not recur during treatment and the patient continued to receive 1.3 mg IM monthly chronically. In another case report, a 32-year old male with idiopathic recurrent priapism received 7.5 mg IM once monthly for 2 months; priapism did not recur as of 4 months after discontinuing the leuprolide. Both patients achieved castration concentrations of testosterone. The American Urological Association recommends GnRH agonist therapy as a first-line option in the prevention of stuttering priapism; however, do not use leuprolide in patients who have not achieved full sexual maturation and adult stature. Additionally, even though patients experience a decrease in libido, most are able to engage in sexual activity.

3.75 mg IM every 4 weeks. When used in patients undergoing chemotherapy, leuprolide is usually initiated about 2 weeks prior to chemotherapy. When proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, gonadotropin-releasing hormone agonists (GnRHa) may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency.

3.75 mg IM every 4 weeks. In one trial, leuprolide injection solution 0.2 mg/day subcutaneously was given daily during the first 2 weeks of treatment so chemotherapy could be started immediately. When proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, gonadotropin-releasing hormone agonists (GnRHa) may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency.

Leuprolide mesylate (Camcevi)
Prostate Cancer: 42 mg subcutaneously every 6 months.
Leuprolide acetate for injectable suspension (Eligard)
Prostate Cancer: 7.5 mg subcutaneously once monthly; OR 22.5 mg subcutaneously every 3 months; OR 30 mg subcutaneously every 4 months; OR 45 mg subcutaneously every 6 months.
Leuprolide acetate for solution (Lupron)
Prostate Cancer: 1 mg subcutaneously once daily.
Leuprolide acetate for depot suspension (Lupron Depot)
Prostate Cancer: 7.5 mg IM once monthly; OR 22.5 mg IM every 3 months; OR 30 mg IM every 4 months; OR 45 mg IM every 6 months.
Endometriosis or Fibroids: 3.75 mg IM once monthly; OR 11.25 mg IM every 3 months.

Leuprolide acetate for injectable suspension (Fensolvi)
45 mg subcutaneously every 6 months.
Leuprolide acetate for depot suspension (Lupron Depot-Ped)
Weight greater than 37.5 kg: 15 mg IM once monthly.
Weight greater than 25 kg up to 37.5 kg: 11.25 mg IM once monthly.

The safety and efficacy of leuprolide acetate has not been established in children younger than 2 years (Fensolvi) or 1 year (Lupron Depot-Ped).
The safety and efficacy of leuprolide mesylate has not been established in children.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

NOTE: Due to the similarity in packaging, dose strengths, and routes of administration for some leuprolide products, always verify the dosage form, product name, intent of use, population of use, and other clinically distinguishing factors prior to administration in order to avoid medication errors.
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Leuprolide is administered subcutaneously or intramuscularly depending upon the formulation.
Injection sites should be rotated periodically.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

NOTE: Take care to verify the correct product and intent of use prior to administration. Due to different release characteristics, Monthly, Three-Month, Four-Month, and Six-Month depot formulations are not equivalent at multiple or fractional doses; apparent equivalent doses from different formulations should not be given. Do not use partial syringes or a combination of syringes to achieve a particular dose.

Leuprolide acetate for depot suspension (Lupron Depot and Lupron Depot-Ped)
Preparation
Visually inspect the powder; do not use if clumping or caking of the powder is evident. A thin layer of powder on the wall of the syringe is normal; the diluent supplied should appear clear.
Use the diluent provided by the manufacturer. Screw the white plunger into the end stopper until the stopper begins to turn. Hold the syringe upright. Release the diluent by slowly pushing the plunger for 6 to 8 seconds, until the first stopper is at the blue line in the middle of the barrel.
Keeping the syringe upright, mix the powder thoroughly by shaking the syringe to form a uniform suspension. The suspension should appear milky. If powder adheres to the stopper or caking/clumping is present, tap the syringe to disperse. DO NOT USE if any of the powder has not gone into suspension.
Keeping the syringe upright, advance the plunger to expel air from the syringe.
After reconstitution, the suspension settles very quickly; therefore, mix and administer the suspension immediately. Discard any suspension not used within 2 hours of reconstitution because it does not contain preservatives.
IM injection
Clean the injection site with an alcohol swab prior to injection.
Keeping the syringe upright, pull the needle cap upward without twisting, and advance the plunger to expel the air from the syringe. Insert the needle IM at a 90-degree angle into the gluteal area, anterior thigh, or deltoid and look for blood. If present, blood can be seen through the transparent LuproLoc safety device and would be visible just below the luer lock connection. Do not inject the medicine if blood is present. If no blood is present, administer the entire contents of the syringe IM.
After injection, withdraw the needle from the injection site. Immediately activate the LuproLoc safety device by pushing the arrow forward with the thumb or finger until the device is fully extended and a click is heard or felt.
Rotate injection sites within the same region when dose is next due.[41676] [42683]

Inject appropriate dose subcutaneously. Choose an injection site with sufficient soft or loose subcutaneous tissue (e.g., upper or middle abdominal area, upper buttocks, or other area without excessive pigment, nodules, lesions, or hair); avoid areas with brawny or fibrous subcutaneous tissue or locations that could be rubbed or compressed with a belt or clothing waistband. Periodically rotate the injection site.

Leuprolide Acetate for injection (Lupron)
Preparation
Use the syringes provided by the manufacturer. If it is absolutely necessary to use a different syringe, only a low-dose insulin syringe should be used.
After removing the syringe from the outer wrapping, pull the plunger back until the tip is at the 0.2 mL or 20 unit mark.
Remove the cover from the needle and push the needle through the rubber stopper. Push the plunger all the way in to inject air into the bottle.
Turn the bottle upside down, making sure the tip of the needle is in the liquid. Slowly pull back on the plunger until the syringe fills to the 0.2 mL or 20 unit mark.
With the needle still in the bottle and the bottle upside down, check for air bubbles in the syringe. Slowly push any air bubbles back into the bottle and pull the plunger back again to fill to the 0.2 mL or 20 unit mark.
Subcutaneous injection
Cleanse the injection spot with alcohol. Hold the skin taut, or pull up a little flesh with the hand not holding the syringe.
Hold the syringe as you would a pencil and thrust the needle into the skin at a 90-degree angle. Push the plunger to administer the injection.
Hold an alcohol wipe on your skin where the needle is inserted and withdraw the needle at the same angle it was inserted. Properly dispose of the syringe.

Leuprolide acetate for injectable suspension (Eligard)
Preparation
Allow the product to reach room temperature before mixing. Once mixed, the product must be administered within 30 minutes.
Pull out the short blue plunger rod with the gray stopper from Syringe B and discard. Twist the white replacement plunger rod into the gray primary stopper remaining in syringe B.
Unscrew and discard the clear cap from Syringe A. Remove and discard the gray rubber cap from Syringe B. Join the two syringes together by pushing in and twisting until secure.
Mix the product by pushing the contents of both syringes back and forth between the syringes (approximately 45 seconds) to obtain a uniform suspension. When thoroughly mixed, the suspension will appear a light tan to tan color or colorless to pale yellow. NOTE: The product must be mixed as described; shaking the product will not provide adequate mixing of the product.
Hold syringes vertically with syringe B on the bottom. Draw the entire mixed product into syringe B (short, wide syringe) by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger. Uncouple Syringe A while continuing to push down on the Syringe A plunger. Small air bubbles will remain in the formulation and this is acceptable.
Hold Syringe B upright. Attach the needle cartridge to the end of Syringe B.
Remove the clear needle cover or protective needle sheath prior to administration. Administer as a single dose subcutaneously.
Subcutaneous injection
Cleanse the injection spot with alcohol. Grab and bunch the area of skin around the injection site.
Using your dominant hand, insert the needle into the skin quickly at a 90-degree angle, then release the skin. Inject the drug using a slow, steady push until the syringe is empty. Withdraw the needle at the same angle it was inserted.
If using a safety needle, activate the safety shield immediately following withdrawal by using a thumb, finger, or flat surface to push it forward until it completely covers the needle tip and locks into place; there will be an audible and tactile "click".
Properly dispose of the syringe.

Leuprolide acetate for injectable suspension (Fensolvi)
Preparation
Allow the product to reach room temperature before mixing. Once mixed, the product must be administered within 30 minutes.
Prepare the 2 syringes for mixing per manufacturer's instructions. Join the 2 syringes together by pushing in and twisting until secure.
Mix the product by pushing the contents of both syringes back and forth between the syringes (approximately 45 seconds) to obtain a uniform suspension. When thoroughly mixed, the suspension will appear pale yellow. NOTE: The product must be mixed as described; shaking the product will not provide adequate mixing of the product.
Hold syringes vertically with Syringe B on the bottom. Draw the entire mixed product into Syringe B (wide syringe) by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger. Uncouple Syringe A while continuing to withdraw the Syringe B plunger. Small air bubbles will remain in the formulation and this is acceptable.
Hold Syringe B upright. Hold back the white plunger on Syringe B to prevent loss of the product. Attach the needle cartridge to the end of Syringe B.
Remove the clear needle cover prior to administration. Administer as a single dose subcutaneously.
Subcutaneous injection
Leuprolide acetate (Fensolvi) must be administered to a healthcare provider.
Cleanse the injection spot with alcohol. Grab and bunch the area of skin around the injection site.
Using your dominant hand, insert the needle quickly at a 90-degree angle to the skin surface. After the needle is inserted, release the skin. Inject the drug using a slow, steady push until the syringe is empty. Withdraw the needle at the same angle it was inserted.
Activate the safety shield immediately following withdrawal by using a thumb, finger, or flat surface to push it forward until it completely covers the needle tip and locks into place; there will be an audible and tactile "click".
Properly dispose of the syringe.[65368]

Leuprolide mesylate injectable emulsion (Camcevi)
Preparation
Remove kit from the refrigerator. Allow it to sit at room temperature for 30 minutes prior to administration.
Remove the prefilled syringe and needle cartridge from the blister carton. Remove the gray cap from the syringe and twist the clear cap off the bottom of the needle cartridge. Attach the needle to the syringe.
Subcutaneous injection
Leuprolide mesylate (Camcevi) must be administered to a healthcare provider.
Grab and bunch the skin around the injection site with one hand. Insert the needle at a 90-degree angle to the skin surface, and then release the bunched skin.
Inject the full contents of the syringe with a slow and steady push on the plunger, then withdraw the needle at the same 90-degree angle used for insertion.
Do not apply heat directly to the site of injection.
Do not remove the needle from the syringe. Place the Point-Lok needle protection device (enclosed in the kit) on a secured, flat surface with its largest area touching the surface. Gently insert the exposed needle into the Point-Lok device opening located at the top of the device. When the needle is full inserted, the tip will be sealed and the needle locked firmly into the Point-Lok device. Properly dispose of the used syringe with the needle protected.

Eligard:
- Product in original packaging may be stored at room temperature (59 to 86 degrees F) for up to 8 weeks
- Refrigerate (between 36 and 46 degrees F)
Fensolv:
- Product in original packaging may be stored at room temperature (59 to 86 degrees F) for up to 8 weeks
- Store between 36 to 46 degrees F
Lupron:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not freeze
- Protect from light
- Store below 77 degrees F
- Store in carton until contents are used
Lupron Depot:
- See package insert for detailed storage information
- Store at 77 degrees F; excursions permitted to 59-86 degrees F
Lupron Depot-Ped:
- Store at 77 degrees F; excursions permitted to 59-86 degrees F
Viadur:
- Store at 77 degrees F; excursions permitted to 59-86 degrees F

Patients with benzyl alcohol hypersensitivity should use caution when treated with leuprolide acetate for injection (Lupron) as it is formulated with benzyl alcohol; other formulations of leuprolide acetate and leuprolide mesylate do not contain benzyl alcohol. Symptoms of hypersensitivity are usually local, in the form of erythema and induration at the injection site.

Leuprolide is contraindicated in patients with Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity, hypersensitivity to leuprolide, or hypersensitivity to GnRH; anaphylactic reactions to synthetic GnRH or GnRH agonists have been reported.

Leuprolide may cause a sudden onset or worsening of prostate cancer or breast cancer symptoms (flare) due to transient increases in testosterone or estrogen levels, respectively, such as bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction. Patients with urinary tract obstruction or metastatic vertebral lesions should be monitored carefully for signs of renal impairment or spinal cord compression, respectively, during initial leuprolide treatment.

Since leuprolide suppresses the pituitary-gonadal axis, laboratory test interference may occur with diagnostic tests for pituitary insufficiency or other pituitary-gonadal function conducted during treatment and after cessation of therapy. Normal function of the pituitary-gonadal system is usually restored within 4 to 12 weeks after treatment is discontinued; in pediatric patients, normal function may be restored within 6 months.

Leuprolide therapy should not be administered to women with dysfunctional uterine bleeding or undiagnosed vaginal bleeding. During the early phase of leuprolide therapy or after subsequent doses, sex steroids temporarily rise above baseline because of a transient stimulatory effect of the drug; an increase in symptoms may be observed during the first weeks of therapy. In pediatric patients, an increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during this time.

Carefully weigh the risks and benefits of leuprolide therapy in patients with osteopenia or osteoporosis, as well as in patients with risk factors for decreased bone mineral density (BMD) such as chronic alcohol use (more than 3 units per day), tobacco smoking, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD such as anticonvulsants or corticosteroids. Gonadotropin Releasing Hormone (GnRH) analog therapy increases the risk of reduced BMD and may have particular relevance for people 65 years and older. The duration of therapy for the treatment of endometriosis and fibroids should not exceed 12 months due to the risk of loss of BMD. The addition of hormone replacement therapy (norethindrone acetate) to leuprolide therapy for endometriosis or uterine fibroids may be effective in reducing bone mineral loss in women. Once norethindrone is added, do not retreat with leuprolide without combination norethindrone; assess BMD prior to retreatment with leuprolide/norethindrone. It can be anticipated that long periods of medical castration in men with prostate cancer will also have effects on bone density. Additionally, reduced BMD has been reported in published literature and postmarketing reports in pediatric patients with central precocious puberty. Published studies have indicated that after discontinuation of leuprolide therapy, subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected.

Carefully evaluate cardiovascular risk factors when determining a treatment plan for patients with prostate cancer. An increased risk of developing myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of Gonadotropin Releasing Hormone (GnRH) agonists in men; the risk appears to be low based on the reported odds ratios. Monitor patients for signs and symptoms suggestive of cardiac disease; if cardiovascular disease develops, manage according to current clinical practice. At this time, there are no known comparable studies evaluating the risk of cardiovascular disease in women or children taking GnRH agonists for other indications.

Use leuprolide with caution in patients with diabetes mellitus. Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving Gonadotropin Releasing Hormone (GnRH) agonists; diabetes has also been reported in postmarketing experience in pediatric studies with leuprolide. Hyperglycemia may represent the development of diabetes or worsening of glycemic control in patients with pre-existing diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in men receiving leuprolide therapy; manage hyperglycemia or diabetes according to current clinical practice. There are no known comparable epidemiologic studies evaluating the risk of diabetes in women taking GnRH agonists.

Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

Androgen deprivation therapy (e.g., leuprolide) may prolong the QT interval. Consider whether the benefits of leuprolide therapy outweigh the potential risk for QT prolongation in patients with congenital long QT syndrome, electrolyte imbalance (e.g., hypokalemia, hypomagnesemia, hypocalcemia), congestive heart failure, or in patients receiving medications known to prolong the QT interval. Correct any electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes. Also, use leuprolide with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Female patients, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

Use leuprolide with caution in patients with a pre-existing seizure disorder. Seizures have been reported during postmarketing surveillance in patients with a history of epilepsy, cerebrovascular disease, central nervous system anomalies or brain tumor, and patients on concomitant medications that have been associated with seizures. Seizures have also been reported in patients without any risk factors. Manage patients receiving leuprolide who experience convulsions according to current clinical practice.

Use leuprolide with caution in patients with depression and emotional instability; monitor patients for worsening of psychiatric symptoms during treatment with leuprolide. Refer patients with new or worsening depression to a mental health professional, as appropriate. During postmarketing experience, emotional lability, such as crying, irritability, impatience, anger, and aggression were reported. Depression, including rare reports of suicidal ideation and attempt, were reported in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.

Use leuprolide with caution in geriatric patients. First, geriatric patients may be at increased risk for QT prolongation when receiving leuprolide. Second, GnRH analog therapy increases the risk of reduced bone mineral density, which may be particularly relevant for geriatric patients who may be more likely to have osteopenia or osteoporosis.

Formulations of leuprolide acetate that have indications which may be used to treat females (i.e., Fesolvi, Lupron Depot-Ped, Lupron Depot 3.75 mg, and Lupron Depot 11.25 mg) are contraindicated in pregnancy; the safety and efficacy of other formulations of leuprolide acetate and mesylate which are only indicated for men (i.e., Camcevi, Eligard, Lupron, and Lupron Depot) have not been established in females. Females may also be at increased risk of a prolonged QT interval with leuprolide use. Although there are no adequately controlled studies in pregnant women, leuprolide can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies, including an increased risk of pregnancy complications such as early pregnancy loss. Women who are pregnant or who become pregnant while receiving leuprolide should be apprised of the potential hazard to the fetus. In animal reproduction studies, subcutaneous administration of leuprolide aetate to rabbits during organogenesis caused embryofetal toxicity, decreased fetal weights, and a dose-dependent increase in major fetal abnormalities in animals at doses less than the recommended human dose based on body surface area (BSA). A similar rat study also showed increased fetal mortality and decreased fetal weights, but no major fetal abnormalities, at doses less than the recommended human dose based on BSA.

Contraception requirements, infertility, pregnancy testing, reproductive risk

Counsel patients about the reproductive risk and contraception requirements during leuprolide treatment. Leuprolide can cause fetal harm or death if taken by the mother during pregnancy. When used at the recommended dose and dosing interval, leuprolide usually inhibits ovulation and stops menstruation; however, contraception is not ensured by taking leuprolide. Females of reproductive potential should avoid pregnancy and use effective non-hormonal contraception during treatment with leuprolide. Females of reproductive potential should undergo pregnancy testing prior to initiation of leuprolide. Women who become pregnant while receiving leuprolide should be apprised of the potential hazard to the fetus. Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, infertility is expected while on treatment with leuprolide. Clinical and pharmacologic studies in adults with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.

There are no data on the presence of leuprolide in human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition when treating patients with Lupron Depot 3.25 mg, Lupron Depot 11.25 mg, Lupron Depot-Ped, or Fensolvi. Although Lupron, Lupron Depot, Eligard, and Camcevi are not indicated in women, due to the potential for serious adverse reactions in nursing infants from leuprolide, advise women to discontinue breast-feeding if they are receiving treatment with these products.

epididymitis / Delayed / 0-5.0
renal tubular obstruction / Delayed / 0-5.0
visual impairment / Early / 0-5.0
seizures / Delayed / 0-5.0
GI bleeding / Delayed / 0-5.0
peptic ulcer / Delayed / 0-5.0
GI obstruction / Delayed / 0-5.0
bone fractures / Delayed / 0-5.0
atrial fibrillation / Early / 0-5.0
myocardial infarction / Delayed / 0-5.0
arrhythmia exacerbation / Early / 0-5.0
heart failure / Delayed / 0-5.0
pulmonary embolism / Delayed / 0-5.0
bradycardia / Rapid / 0-5.0
thromboembolism / Delayed / 0-5.0
pulmonary edema / Early / 0-5.0
pulmonary fibrosis / Delayed / 0-5.0
pleural effusion / Delayed / 0-5.0
feminization / Delayed / 0-2.0
thrombosis / Delayed / 2.0-2.0
erythema multiforme / Delayed / 0-0.1
anaphylactoid reactions / Rapid / 0-0.1
muscle paralysis / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
rectal fistula / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
ovarian hyperstimulation syndrome / Delayed / Incidence not known
pituitary apoplexy / Early / Incidence not known
stroke / Early / Incidence not known

hot flashes / Early / 5.0-73.3
edema / Delayed / 0-20.8
testicular atrophy / Delayed / 0-20.2
peripheral edema / Delayed / 0-12.0
constipation / Delayed / 0-9.9
dehydration / Delayed / 0-8.2
hypertension / Early / 0-8.0
hematuria / Delayed / 0-6.0
impotence (erectile dysfunction) / Delayed / 0-5.4
depression / Delayed / 0-5.3
anemia / Delayed / 0-5.0
peripheral neuropathy / Delayed / 0-5.0
hyperesthesia / Delayed / 0-5.0
bone pain / Delayed / 0-5.0
urinary incontinence / Early / 0-5.0
bladder spasm / Early / 0-5.0
dysuria / Early / 0-5.0
amnesia / Delayed / 0-5.0
confusion / Early / 0-5.0
memory impairment / Delayed / 0-5.0
amblyopia / Delayed / 0-5.0
blurred vision / Early / 0-5.0
hepatomegaly / Delayed / 0-5.0
dysphagia / Delayed / 0-5.0
impaired wound healing / Delayed / 0-5.0
diabetes mellitus / Delayed / 0-5.0
lymphadenopathy / Delayed / 0-5.0
hypotension / Rapid / 0-5.0
angina / Early / 0-5.0
hypoxia / Early / 0-5.0
dysphonia / Delayed / 0-5.0
hemoptysis / Delayed / 0-5.0
urinary retention / Early / 0-4.6
vaginitis / Delayed / 3.0-3.0
vaginal bleeding / Delayed / 3.0-3.0
skin ulcer / Delayed / 0-3.0
colitis / Delayed / 2.5-2.5
growth inhibition / Delayed / 0-2.0
goiter / Delayed / 0-2.0
myopathy / Delayed / 0-2.0
phlebitis / Rapid / 2.0-2.0
dyspnea / Early / 2.0-2.0
hyperuricemia / Delayed / 5.0
hyperphosphatemia / Delayed / 5.0
hyperglycemia / Delayed / 5.0
hyperlipidemia / Delayed / 5.0
leukopenia / Delayed / 5.0
eosinophilia / Delayed / 5.0
prostate pain / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
pyuria / Delayed / Incidence not known
euphoria / Early / Incidence not known
hyperreflexia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
hematoma / Early / Incidence not known
ovarian enlargement / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
osteoporosis / Delayed / Incidence not known
synovitis / Delayed / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
thrombocytopenia / Delayed / Incidence not known

injection site reaction / Rapid / 0-37.5
ecchymosis / Delayed / 0-34.6
musculoskeletal pain / Early / 0-32.7
pharyngitis / Delayed / 22.0-22.0
fatigue / Early / 0-17.5
fever / Early / 17.0-17.0
headache / Early / 0-16.0
cough / Delayed / 1.3-13.0
asthenia / Delayed / 0-12.2
skin irritation / Early / 0-12.2
infection / Delayed / 0-12.2
arthralgia / Delayed / 0-9.3
abdominal pain / Early / 0-9.0
insomnia / Early / 0-8.5
dizziness / Early / 0-8.3
paresthesias / Delayed / 0-8.2
myalgia / Early / 0-8.2
nausea / Early / 0-8.0
gynecomastia / Delayed / 2.2-7.0
mastalgia / Delayed / 3.1-7.0
increased urinary frequency / Early / 2.2-6.0
urinary urgency / Early / 0-6.0
vomiting / Early / 0-6.0
anorexia / Delayed / 0-6.0
libido decrease / Delayed / 3.3-5.4
hyperhidrosis / Delayed / 0-5.3
breast enlargement / Delayed / 0-5.0
anxiety / Delayed / 0-5.0
syncope / Early / 0-5.0
emotional lability / Early / 0-5.0
xerophthalmia / Early / 0-5.0
dysgeusia / Early / 0-5.0
parosmia / Delayed / 0-5.0
agitation / Early / 0-5.0
lethargy / Early / 0-5.0
tinnitus / Delayed / 0-5.0
diarrhea / Early / 0-5.0
weight loss / Delayed / 0-5.0
appetite stimulation / Delayed / 0-5.0
xerostomia / Early / 0-5.0
gingivitis / Delayed / 0-5.0
melasma / Delayed / 0-5.0
alopecia / Delayed / 0-5.0
skin hyperpigmentation / Delayed / 0-5.0
xerosis / Delayed / 0-5.0
ptosis / Delayed / 0-5.0
muscle cramps / Delayed / 0-5.0
chills / Rapid / 0-5.0
hiccups / Early / 0-5.0
epistaxis / Delayed / 0-5.0
testicular pain / Early / 3.8-3.8
nocturia / Early / 0-3.8
weakness / Early / 3.6-3.6
night sweats / Early / 2.7-3.3
vaginal discharge / Delayed / 3.0-3.0
seborrhea / Delayed / 3.0-3.0
rash / Early / 0-3.0
weight gain / Delayed / 0-2.3
dysmenorrhea / Delayed / 0-2.0
back pain / Delayed / 0-2.0
vertigo / Early / 0-2.0
malaise / Early / 0-2.0
flatulence / Early / 0-2.0
dyspepsia / Early / 0-2.0
skin hypopigmentation / Delayed / 0-2.0
purpura / Delayed / 0-2.0
urticaria / Rapid / 0-0.1
photosensitivity / Delayed / 0-0.1
eructation / Early / 5.0
amenorrhea / Delayed / Incidence not known
libido increase / Delayed / Incidence not known
tremor / Early / Incidence not known
hyporeflexia / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
influenza / Delayed / Incidence not known
rhinitis / Early / Incidence not known
sinusitis / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
rhinorrhea / Early / Incidence not known

Alfuzosin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving alfuzosin. Androgen deprivation therapy may prolong the QT/QTc interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) Avoid coadministration of amiodarone with triptorelin if possible due to the risk of QT prolongation. Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), although the frequency of TdP is less with amiodarone than with other Class III agents. Androgen deprivation therapy also prolongs the QT interval. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with leuprolide. Amisulpride causes dose- and concentration- dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Amoxapine: (Major) Avoid coadministration of leuprolide with amoxapine due to the risk of reduced efficacy of leuprolide. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval such as leuprolide. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide; in addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
Androgens: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Apomorphine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving aripiprazole. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of aripiprazole and following overdose.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with leuprolide; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with leuprolide if possible due to the risk of QT prolongation. Consider ECG monitoring if leuprolide must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. (Major) Avoid coadministration of lumefantrine with leuprolide if possible due to the risk of QT prolongation. Consider ECG monitoring if leuprolide must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Asenapine: (Major) Avoid coadministration of leuprolide with asenapine due to the risk of reduced efficacy of leuprolide as well as the risk of QT prolongation. Asenapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, asenapine has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Atomoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving atomoxetine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
Azithromycin: (Major) Avoid coadministration of azithromycin with leuprolide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Androgen deprivation therapy may prolong the QT/QTc interval.
Bedaquiline: (Major) Frequently monitor ECGs for QT prolongation if coadministration of bedaquiline with leuprolide is necessary. Bedaquiline has been reported to prolong the QT interval; coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brexpiprazole: (Major) Avoid coadministration of leuprolide with brexpiprazole due to the risk of reduced efficacy of leuprolide. Brexpiprazole can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Buprenorphine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Buprenorphine; Naloxone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving buprenorphine. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Cabotegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Cariprazine: (Major) Avoid coadministration of leuprolide with cariprazine due to the risk of reduced efficacy of leuprolide. Cariprazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Ceritinib: (Major) Avoid coadministration of ceritinib with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Chloroquine: (Major) Avoid coadministration of chloroquine with leuprolide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Chlorpromazine: (Major) Avoid coadministration of leuprolide with chlorpromazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Ciprofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ciprofloxacin. Androgen deprivation therapy may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance.
Cisapride: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), the use of leuprolide with cisapride is contraindicated. Prolongation of the QT interval and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
Citalopram: (Major) Coadministration of citalopram with leuprolide is not recommended due to the risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with leuprolide. Prolongation of the QT interval and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Clozapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clozapine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Androgen deprivation therapy may prolong the QT/QTc interval.
Codeine; Phenylephrine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Codeine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Crizotinib: (Major) Avoid coadministration of crizotinib with leuprolide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Androgen deprivation therapy (e.g., leuprolide) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
Danazol: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Dasatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
Desflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Deutetrabenazine: (Major) Avoid coadministration of leuprolide with deutetrabenazine due to the risk of reduced efficacy of leuprolide. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dextromethorphan; Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Disopyramide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
Dofetilide: (Major) Coadministration of dofetilide and leuprolide is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Dolasetron: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Donepezil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving donepezil. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Donepezil; Memantine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving donepezil. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Androgen deprivation therapy (e.g., leuprolide) may also prolong the QT/QTc interval.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as leuprolide. If coadministration is unavoidable, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Efavirenz: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
Eliglustat: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Encorafenib: (Major) Avoid coadministration of encorafenib and leuprolide due to the risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Enflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Entrectinib: (Major) Avoid coadministration of entrectinib with leuprolide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Eribulin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with leuprolide is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Erythromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Erythromycin; Sulfisoxazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving erythromycin. Erythromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Escitalopram: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving escitalopram as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
Esterified Estrogens; Methyltestosterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Ezogabine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ezogabine. Androgen deprivation therapy may prolong the QT/QTc interval. Ezogabine has also been associated with QT prolongation.
Fingolimod: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fingolimod as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving flecainide. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fluconazole has also been associated with QT prolongation as well as rare cases of torsade de pointes (TdP).
Fluoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving fluoxetine. Coadministration of fluoxetine and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy may prolong the QT/QTc interval.
Fluoxymesterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Fluphenazine: (Major) Avoid coadministration of leuprolide with fluphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Fluphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluvoxamine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving fluvoxamine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval and torsade de pointes (TdP) has also been reported during fluvoxamine post-marketing use.
Foscarnet: (Major) Avoid coadministration of foscarnet with leuprolide due to the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet.
Fostemsavir: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving gemifloxacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Androgen deprivation therapy may also prolong the QT/QTc interval.
Gemtuzumab Ozogamicin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and leuprolide due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and leuprolide is necessary as concurrent use may increase the risk of QT prolongation. Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Gilteritinib has also been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with leuprolide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Granisetron: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
Halogenated Anesthetics: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of leuprolide with haloperidol due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Halothane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Hydroxychloroquine: (Major) Avoid coadministration of leuprolide and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Androgen deprivation therapy (e.g., leuprolide) also may prolong the QT/QTc interval.
Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with leuprolide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
Ibutilide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Iloperidone: (Major) Avoid coadministration of leuprolide with iloperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Iloperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Iloperidone has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with leuprolide due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide ) may prolong the QT/QTc interval.
Isoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Itraconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving itraconazole as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with leuprolide if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Androgen deprivation therapy (i.e., leuprolide) also may prolong the QT/QTc interval.
Ketoconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ketoconazole as concurrent use may increase the risk of QT prolongation. Ketoconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Lapatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving lapatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Avoid coadministration of lefamulin with leuprolide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with leuprolide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Levofloxacin has also been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
Levoketoconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ketoconazole as concurrent use may increase the risk of QT prolongation. Ketoconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Lithium: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving lithium. Lithium has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Lofexidine: (Moderate) Monitor ECGs for QT prolongation if coadministration of lofexidine with leuprolide is necessary. Lofexidine prolongs the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Loperamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval.
Loperamide; Simethicone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with leuprolide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Lorcaserin: (Major) Avoid coadministration of leuprolide with lorcaserin due to the risk of reduced efficacy of leuprolide. Lorcaserin can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Loxapine: (Major) Avoid coadministration of leuprolide with loxapine due to the risk of reduced efficacy of leuprolide. Loxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as leuprolide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Maprotiline: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Meperidine; Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Methadone: (Major) Coadministration of methadone with leuprolide should be undertaken with extreme caution and a careful assessment of the benefits of therapy versus the risks of QT prolongation. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Androgen deprivation therapy may prolong the QT/QTc interval.
Methyldopa: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Methyltestosterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Metoclopramide: (Major) Avoid coadministration of leuprolide with metoclopramide due to the risk of reduced efficacy of leuprolide. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Metronidazole: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Consider periodic monitoring of EGCs for QT prolongation if coadministration of leuprolide and midostaurin is necessary. Prolongation of the QT interval was reported in patients who received midostaurin in clinical trials. Androgen deprivation therapy (i.e., leuprolide ) may also prolong the QT/QTc interval.
Mifepristone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
Mirtazapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mirtazapine. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported in postmarketing experience, primarily in overdose or in patients with other risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Mobocertinib: (Major) Concomitant use of mobocertinib and androgen deprivation therapy (i.e. leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Major) Avoid coadministration of leuprolide with molindone due to the risk of reduced efficacy of leuprolide. Molindone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Moxifloxacin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving moxifloxacin. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, torsade de pointes (TdP) has been reported during postmarketing surveillance of moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Androgen deprivation therapy may also prolong the QT/QTc interval.
Nandrolone Decanoate: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Nilotinib: (Major) Avoid administration of nilotinib with leuprolide due to the risk of QT interval prolongation. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Octreotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
Ofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving leuprolide as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Ofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin.
Olanzapine: (Major) Avoid coadministration of leuprolide with olanzapine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of leuprolide with olanzapine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks in patients receiving fluoxetine. Coadministration of fluoxetine and leuprolide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy may prolong the QT/QTc interval.
Olanzapine; Samidorphan: (Major) Avoid coadministration of leuprolide with olanzapine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Ondansetron: (Major) Monitor ECGs for QT prolongation if coadministration of ondansetron with leuprolide is necessary. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with leuprolide. Osilodrostat is associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Osimertinib: (Major) Avoid coadministration of leuprolide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Oxaliplatin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with leuprolide; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Oxandrolone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Oxymetholone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Pacritinib: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e. leuprolide) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Avoid coadministration of leuprolide with paliperidone due to the risk of reduced efficacy of leuprolide and the risk of QT prolongation. Paliperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Panobinostat: (Major) Coadministration of panobinostat with leuprolide is not recommended due to the risk of QT prolongation. Prolongation of the QT interval has been reported with panobinostat treatment. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Pasireotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
Pazopanib: (Major) Coadministration of pazopanib and leuprolide is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Pentamidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
Perphenazine: (Major) Avoid coadministration of leuprolide with perphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Perphenazine; Amitriptyline: (Major) Avoid coadministration of leuprolide with perphenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Pimavanserin: (Major) Coadministration of pimavanserin with leuprolide should generally be avoided due to the risk of QT prolongation. Pimavanserin may cause QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with pimozide is contraindicated; the efficacy of leuprolide may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Pitolisant: (Major) Avoid coadministration of pitolisant with leuprolide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Posaconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Primaquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has the potential to cause QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Procainamide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Prochlorperazine: (Major) Avoid coadministration of leuprolide with prochlorperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Prochlorperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Promethazine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Promethazine; Dextromethorphan: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Promethazine; Phenylephrine: (Major) Avoid coadministration of leuprolide with promethazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Promethazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Propafenone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving propafenone. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Quetiapine: (Major) Avoid coadministration of quetiapine with leuprolide due to the risk of QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
Quinine: (Major) Avoid coadministration of quinine with leuprolide due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Ramelteon: (Major) Avoid coadministration of leuprolide with ramelteon due to the risk of reduced efficacy of leuprolide. Ramelteon can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Ranolazine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ranolazine as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Androgen deprivation therapy may prolong the QT/QTc interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Reserpine: (Major) Avoid coadministration of leuprolide with reserpine due to the risk of reduced efficacy of leuprolide. Reserpine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Ribociclib: (Major) Avoid coadministration of ribociclib with leuprolide due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with leuprolide due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Risperidone: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Romidepsin: (Moderate) Monitor ECGs and monitor electrolytes at baseline and periodically during treatment if coadministration of romidepsin with leuprolide is necessary as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Saquinavir: (Major) Avoid coadministration of saquinavir with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, perform a baseline ECG prior to initiation of therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with leuprolide is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Sertraline: (Moderate) Consider whether the benefits of leuprolide therapy outweigh the potential risk of QT prolongation in patients receiving sertraline. If use together is necessary, use caution and monitor patients for QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
Sevoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving leuprolide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Solifenacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
Sorafenib: (Major) Avoid coadministration of sorafenib with leuprolide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Sotalol: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving sotalol. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Androgen deprivation therapy may also prolong the QT/QTc interval.
Sunitinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Consider the benefits of androgen deprivation therapy and monitor ECG and electrolytes periodically during treatment if tacrolimus is administered with leuprolide. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Tamoxifen: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tamoxifen. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses; rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Androgen deprivation therapy may prolong the QT/QTc interval.
Telavancin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telavancin as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Telithromycin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
Testosterone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Tetrabenazine: (Major) Avoid coadministration of leuprolide with tetrabenazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Tetrabenazine can cause leuprolide, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with thioridazine is contraindicated; the efficacy of leuprolide may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Thiothixene: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Tolterodine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Androgen deprivation therapy may also prolong the QT/QTc interval.
Toremifene: (Major) Avoid coadministration of leuprolide with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Trandolapril; Verapamil: (Major) Avoid coadministration of leuprolide with verapamil due to the risk of reduced efficacy of leuprolide. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Trazodone: (Major) Avoid coadministration of trazodone with leuprolide due to the risk of QT prolongation. Trazodone can prolong the QT/QTc interval at therapeutic doses; in addition, there are postmarketing reports of torsade de pointes (TdP). Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Triclabendazole: (Moderate) Monitor ECGs in patients receiving triclabendazole with leuprolide. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Trifluoperazine: (Major) Avoid coadministration of leuprolide with trifluoperazine due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Valbenazine: (Major) Avoid concurrent use of leuprolide with valbenazine due to the risk of reduced efficacy of leuprolide. Valbenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Vandetanib: (Major) Avoid coadministration of vandetanib with leuprolide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Vardenafil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Vemurafenib: (Major) Closely monitor ECGs for QT prolongation if coadministration of vemurafenib with leuprolide is necessary. Vemurafenib has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Venlafaxine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Verapamil: (Major) Avoid coadministration of leuprolide with verapamil due to the risk of reduced efficacy of leuprolide. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Voclosporin: (Moderate) Concomitant use of voclosporin and leuprolide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Voriconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving voriconazole as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Androgen deprivation therapy may also prolong the QT/QTc interval.
Vorinostat: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Ziprasidone: (Major) Concomitant use of ziprasidone and leuprolide should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.

Leuprolide is a synthetic nonapeptide analog of naturally occurring Gonadotropin Releasing Hormone (GnRH) that possesses greater potency than the natural hormone. As a long-acting GnRH agonist, it acts as a potent inhibitor of gonadotropin secretion (luteinizing hormone [LH] and follicle stimulating hormone [FSH]) when given continuously in therapeutic doses. In both animal and human studies, after an initial stimulation of pituitary gonadotropins, chronic administration results in a down-regulation of GnRH receptors, reduction in the release of LH and FSH, and consequent suppression of ovarian and testicular steroidogenesis. Consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent. This effect is reversible after discontinuation of therapy.
In humans, subcutaneous administration of single daily doses of leuprolide initial increases circulating levels of LH and FSH, which transiently increases levels of gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous daily administration decreases LH and FSH concentrations. In males, testosterone concentrations are reduced to below castration levels (50 ng/dL or less) within 2 to 4 weeks after initiation of treatment; castration levels of testosterone in men with prostate cancer have been demonstrated for up to 7 years. Normal function of the pituitary-gonadal system is usually restored within 3 months after treatment is discontinued; diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and for up to 3 months after discontinuation may be affected.
Administration of leuprolide inhibits growth of certain hormone-dependent tumors (prostatic tumors in Noble and Dunning male rats and DMBA-induced mammary tumors in female rats) as well as atrophy of the reproductive organs.

Leuprolide is administered subcutaneously or intramuscularly; it is not active when administered orally. In vitro binding to human protein ranged from 43% to 49%. The mean steady-state volume of distribution was 27 liters after an IV bolus in healthy male volunteers. The mean systemic clearance of leuprolide was 7.6 L/hour to 8.34 L/hour after an IV bolus in healthy male volunteers, with a terminal elimination half-life estimated to be about 3 hours based on a 2-compartment model. Leuprolide is metabolized to smaller inactive peptides including a pentapeptide which is the major metabolite (Metabolite I; M1), tripeptides (Metabolites II and III), and a dipeptide (Metabolite IV) which may then be further catabolized. Plasma concentrations of M1 were approximately 6% of the peak parent drug concentration; one week after dosing, mean M1 concentrations were approximately 20% of mean leuprolide concentrations. Following IM administration of leuprolide to 3 patients, less than 5% of the dose was recovered in the urine as parent and M1 metabolite. The excretion of leuprolide has not been evaluated with the extended-release subcutaneous formulations (i.e., Eligard, Fensolvi, and Camcevi).

Affected cytochrome P450 isoenzymes: None
Leuprolide acetate is primarily degraded by peptidase. Although drug interaction studies have not been conducted, leuprolide is not degraded by CYP450 enzymes thus drug interactions associated with these enzymes are not expected to occur.

The Cmax of leuprolide ranged from 4.6 ng/mL to 10.2 ng/mL at 4 hours after a single IM injection of leuprolide 3.75 mg in healthy female volunteers; after the initial rise, leuprolide concentrations began to plateau within 2 days after dosing and remained relatively stable for 4 to 5 weeks with plasma concentrations of about 0.3 ng/mL. After a single IM injection of leuprolide 11.25 mg in female subjects, a mean plasma concentration of 36.3 ng/mL was observed at 4 hours; mean levels declined to near the lower limit of detection by 12 weeks, with the mean leuprolide concentration from 3 to 12 weeks at 0.23 +/- 0.09 ng/mL. There was no statistically significant difference in changes of serum estradiol concentrations from baseline in a pharmacokinetic/pharmacodynamic study of endometriosis patients treated with leuprolide 3.75 mg IM every 4 weeks or 11.25 mg IM every 12 weeks. Mean peak plasma concentrations were 20 ng/mL, 48.9 ng/mL, and 59.3 ng/mL at 4 hours after administration in patients after a single IM injection of leuprolide acetate 7.5 mg, 22.5 mg, and 30 mg, respectively; mean peak plasma concentrations of 6.7 ng/mL were observed 2 hours after IM administration of leuprolide acetate 45 mg. Plasma concentrations decreased to 0.36 ng/mL 4 weeks after administration of leuprolide 7.5 mg; 0.67 ng/mL 12 weeks after administration of 22.5 mg; 0.3 ng/mL 16 weeks after administration of 30 mg; and 0.07 ng/mL 24 weeks after administration of 45 mg. Plasma concentrations of M1 in prostate cancer patients (n = 5) reached maximum concentrations 2 to 6 hours after dosing. For the 3-month, 4-month, and 6-month formulations, the initial peak followed by a decline to steady-state concentrations was similar to the release pattern seen with the monthly formulation. Intact leuprolide and an inactive major metabolite could not be distinguished by the assay employed in the studies. Leuprolide appears to be released at a constant rate following the onset of steady-state concentrations during the third week after dosing, providing steady plasma concentrations through the dosing interval.

The bioavailability of leuprolide after subcutaneous administration is comparable to that by IV injection. Leuprolide concentrations are variable, exhibiting an initial rapid increase followed by a rapid decline over the first 3 days before reaching steady concentrations for the remainder of the dosing interval. The mean Cmax of leuprolide mesylate (Camcevi)was 94.5 ng/mL to 99 ng/mL, with mean serum concentrations maintained between 0.497 ng/mL to 2.57 ng/mL after the third day; the median Tmax was 2.1 to 3.2 hours. The mean AUC was between 224 ng x day/mL and 268 ng x day/mL. The mean Cmax of leuprolide acetate (Eligard) after subcutaneous administration to men with prostate cancer was 25.3 ng/mL for those receiving 7.5 mg once monthly; 107 ng/mL to 127 ng/mL for those receiving 22.5 mg every 3 months; 150 ng/mL for those receiving 30 mg every 4 months, and 82 ng/mL to 102 ng/mL for those receiving 45 mg every 6 months. The Tmax ranged from 3.3 to 5 hours in these patients. After the initial increase following each injection, serum concentrations remained relatively consistent at 0.28 ng/mL to 2 ng/mL for the 7.5 mg dose; 0.2 ng/mL to 2 ng/mL for the 22.5 mg and 45 mg doses; and 0.1 ng/mL to 1 ng/mL for the 30 mg dose. There was no evidence of significant accumulation during repeated dosing. Although nondetectable leuprolide plasma concentrations have occasionally been observed, testosterone concentrations were maintained at castrate levels.

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leuprolide acetate (Lupron)- Drug Summary

DESCRIPTION

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