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  • CLASSES

    Cytostatic Gonadotropin-releasing Hormone Analogs
    Gonadotropin Releasing Hormone Receptor Antagonist

    DEA CLASS

    Rx

    DESCRIPTION

    GnRH antagonist for advanced prostate cancer; weak histamine releasing potential; more rapid and profound testosterone suppression compared to other GnRH antagonists; no initial increase in serum testosterone or estrogen concentrations.

    COMMON BRAND NAMES

    Firmagon

    HOW SUPPLIED

    Firmagon Subcutaneous Inj Pwd F/Sol: 80mg, 120mg

    DOSAGE & INDICATIONS

    For the treatment of advanced prostate cancer.
    NOTE: Two strengths are available. The 120 mg strength (used for the initial dose) contains 120 mg in 3 mL once reconstituted. The 80 mg strength (used for the maintenance dose) contains 80 mg in 4 mL once reconstituted. Double check the vial strength to ensure accuracy prior to administering.
    Subcutaneous dosage
    Adults

    As an initial dose, administer 240 mg subcutaneously as 2 separate 120 mg subcutaneous injections, then after 28 days, give 80 mg subcutaneously every 28 days to maintain suppression of testosterone. The effectiveness of degarelix has been evaluated over a 12 month period. Of the 207 patients that received degarelix, 97.2% achieved and maintained testosterone concentrations 50 ng/dL or less.

    MAXIMUM DOSAGE

    Adults

    240 mg subcutaneously.

    Geriatric

    240 mg subcutaneously.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustment in patients with hepatic impairment are not available; data are limited in patients with severe impairment (Child-Pugh class C). For all patients, monitor testosterone concentrations monthly until medical castration (testosterone concentration <=50 ng/dL) is achieved. Once medical castration is achieved, consider monitoring testosterone concentrations every-other-month.

    Renal Impairment

    Specific guidelines for dosage adjustment in patients with renal impairment are not available; data are limited in patients with severe impairment (CrCl < 50 mL/min).

    ADMINISTRATION

    For storage information, see the specific product information within How Supplied section.

    Injectable Administration
    Subcutaneous Administration

    For subcutaneous injection in the abdominal region only. Do NOT administer intravenously.
    Degarelix should only be administered by a healthcare professional.
     
    General reconstitution information:
    Gloves should be worn during preparation and administration; aseptic technique should be followed.
    Keep vials vertical at all times; do NOT shake the vials.
    Administer reconstituted drug within 1 hour (60 minutes) after addition of sterile water for injection (SWI).
     
    Reconstitution of 120 mg vial (240 mg dose ONLY):
     
    NOTE: To achieve a 240 mg dose, two 120 mg vials of degarelix must be used. Therefore, the following instructions will need to be repeated for each 120 mg vial.
    Peel off the seal from the vial adaptor cover; do not touch the vial adaptor.
    Press the vial adapter to the vial until the spike punctures the rubber stopper and the adaptor snaps into place. Pull the vial adaptor cover off the vial.
    Attach the plunger to the prefilled 3 mL syringe of Sterile Water for Injection (SWI). Do not pull the back stopper (flange) off the syringe. You will only feel light resistance screwing the plunger rod in position.
    Unscrew the gray syringe plug attached to the Luer lock adaptor on the syringe; do not pull off the Luer lock adaptor.
    Attach the prefilled syringe with SWI onto the vial adaptor; be careful not to over-twist the syringe.
    Inject the entire volume of SWI from the prefilled syringe slowly into a vial containing 120 mg of degarelix. In order to maintain sterility, do not remove the syringe from the vial.
    Keep the vial in an upright position and swirl gently until the liquid looks clear and without undissolved powder. Avoid shaking to prevent foam formation. The vial can be tilted slightly to dissolve powder. The reconstitution process may take up to 15 minutes, but usually takes a few minutes.
    Turn the vial upside down and withdraw 3 ml (40 mg/mL); remove any air bubbles.
    Remove the syringe from the vial adapter and attach the needle provided in the kit.
    Repeat the constitution procedure with a new vial, needle, and syringe for the second 120 mg dose (total dose = 240 mg)
     
    Reconstitution of 80 mg vial:
    Peel off the seal from the vial adaptor cover; do not touch the vial adaptor.
    Press the vial adapter to the vial until the spike punctures the rubber stopper and the adaptor snaps into place. Pull the vial adaptor cover off the vial.
    Attach the plunger to the prefilled 4.2 mL syringe of Sterile Water for Injection (SWI). Do not pull the back stopper (flange) off the syringe. You will only feel light resistance screwing the plunger rod in position.
    Unscrew the gray syringe plug attached to the Luer lock adaptor on the syringe; do not pull off the Luer lock adaptor.
    Attach the prefilled syringe with SWI onto the vial adaptor; be careful not to over-twist the syringe.
    Inject the entire volume of SWI from the prefilled syringe slowly into vial containing 80 mg of degarelix. In order to maintain sterility, do not remove the syringe from the vial.
    Keep the vial in an upright position and swirl gently until the liquid looks clear and without undissolved powder. Avoid shaking to prevent foam formation. The vial can be tilted slightly to dissolve powder. The reconstitution process may take up to 15 minutes, but usually takes a few minutes.
    Turn the vial upside down and withdraw 4 ml (20 mg/mL); remove any air bubbles
    Remove the syringe from the vial adapter and attach the needle provided in the kit.
     
    Subcutaneous injection:
    Degarelix is administered in the abdominal region in an area not exposed to pressure (e.g. not close to belt area, waistband, close to ribs); injection site should vary.
    Disinfect the area to be injected with an alcohol pad.
    Move the needle shield away from the needle and carefully remove the needle cover.
    Grasp the skin of abdomen, elevate the subcutaneous tissue, and insert the needle deeply at a 45 degree angle, all the way to the needle hub.
    Aspirate prior to injection to ensure a blood vessel has not been penetrated. If blood appears in the syringe, discontinue the procedure and discard the syringe and the needle. The reconstituted product can no longer be used and a new dose must be prepared.
    Slowly inject the dose subcutaneously over 30 seconds. When giving the loading dose, which consists of two 120 mg doses, the second dose should be injected subcutaneously at a different site in the abdomen.
    Remove the needle, and then release the skin. Do not rub the injection site after removing the needle.
    To lock the needle into the shield, position the needle shield about 45 degrees to a flat surface. Press down with a firm, quick motion until a click is heard, and confirm that the needle is fully engaged under the lock.

    STORAGE

    Generic:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Degarelix:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Firmagon:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    As degarelix suppresses the pituitary-gonadal axis, diagnostic tests for pituitary insufficiency or other pituitary-gonadal function conducted during treatment and after cessation of therapy may be misleading.

    Children

    Degarelix is not indicated for use in children.

    Mannitol hypersensitivity

    Degarelix is contraindicated in patients with a known hypersensitivity to the drug or its components. Because degarelix vials contain mannitol, it may be prudent to avoid using in patients with mannitol hypersensitivity.

    Intravenous administration

    Do not administer degarelix by intravenous administration. Degarelix is for subcutaneous administration only.

    Hepatic disease

    The use of degarelix in patients with severe hepatic disease (Child-Pugh class C) has not been studied. Degarelix should be used with caution in patients with severe hepatic disease. In patients without prostate cancer but with mild or moderate hepatic impairment (Child-Pugh class A and B), a single dose of 1 mg degarelix administered as an IV infusion over 1 hour decreased the exposure of degarelix by 10% and 18%, respectively. As hepatic impairment can lower degarelix exposure, monitor testosterone concentrations on a monthly basis until medical castration is achieved. Once medical castration is achieved, consider an every-other-month testosterone monitoring approach.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, geriatric, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    QTc prolongation has been reported with the use of degarelix. Long-term androgen deprivation causes QT prolongation. Use degarelix with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

    Renal disease, renal failure, renal impairment

    Data are limited on the use of degarelix in patients with renal disease, renal impairment, and renal failure. Degarelix should be used with caution in patients with Cr Cl < 50 mL/min. Some degarelix is excreted unchanged in the urine (20—30%).

    Osteoporosis

    Treatment with degarelix may cause a decrease in bone mineral density and should be used with caution in patients with osteoporosis.

    Pregnancy

    Degarelix is not indicated for use in females, and is contraindicated for use in females of childbearing age. According to the manufacturer degarelix is a pregnancy category X drug and should not be used in women who are pregnant or may become pregnant. Embryo and fetal death and abortion occurred when degarelix (0.02% of the clinical loading dose) was administered to rabbits during organogenesis. In rats, degarelix (0.036% of the clinical loading dose) given during organogenesis resulted in an increase in post implantation loss and a decrease in the number of live fetuses. If degarelix is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential risk to the fetus.

    Angioedema, urticaria

    Hypersensitivity reactions such as anaphylaxis, urticaria, and angioedema have been reported with degarelix therapy. Use is contraindicated in patients who have experienced a hypersensitivity reaction to degarelix. Discontinue therapy in patients who develop a serious hypersensitivity reaction; do not rechallenge these patients with degarelix.

    Breast-feeding

    Degarelix is not indicated for use in females. It is unknown if degarelix is excreted in human milk. As a result of the potential for serious adverse events in nursing infants exposed to degarelix, according to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue the drug.

    ADVERSE REACTIONS

    Severe

    injection site reaction / Rapid / 0-2.0
    elevated hepatic enzymes / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    hot flashes / Early / 26.0-26.0
    erythema / Early / 17.0-17.0
    antibody formation / Delayed / 10.0-10.0
    hypertension / Early / 6.0-6.0
    impotence (erectile dysfunction) / Delayed / 0-5.0
    testicular atrophy / Delayed / 0-5.0
    constipation / Delayed / 5.0-5.0
    QT prolongation / Rapid / 0-1.0
    osteoporosis / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known

    Mild

    weight gain / Delayed / 9.0-9.0
    back pain / Delayed / 6.0-6.0
    night sweats / Early / 1.0-5.0
    insomnia / Early / 1.0-5.0
    gynecomastia / Delayed / 0-5.0
    hyperhidrosis / Delayed / 0-5.0
    fever / Early / 1.0-5.0
    chills / Rapid / 5.0-5.0
    infection / Delayed / 5.0-5.0
    arthralgia / Delayed / 5.0-5.0
    asthenia / Delayed / 1.0-5.0
    headache / Early / 1.0-5.0
    dizziness / Early / 1.0-5.0
    diarrhea / Early / 0-5.0
    nausea / Early / 1.0-5.0
    fatigue / Early / 3.0-3.0
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Alfuzosin: (Major) Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with alfuzosin include degarelix.
    Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with amiodarone include degarelix.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include clarithromycin.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include clarithromycin.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include degarelix.
    Androgens: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Apomorphine: (Major) Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with apomorphine include degarelix.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include degarelix.
    Artemether; Lumefantrine: (Major) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be avoided with artemether; lumefantrine include degarelix. If coadministration is necessary, use with caution and consider ECG monitoring.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be avoided in combination with asenapine include degarelix. In addition, this combination should be avoided since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include degarelix.
    Azithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering degarelix and azithromycin. Degarelix can cause QT prolongation, and azithromycin has been associated with cases of QT prolongation and TdP during the post-marketing period. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking azithromycin.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with degarelix. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include degarelix.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include degarelix.
    Bretylium: (Severe) Degarelix can cause QT prolongation. Because of the potential for torsade pointes (TdP), use of bretylium with degarelix is contraindicated.
    Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with degarelix. 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, such as degarelix. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with degarelix. 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, such as degarelix. If these drugs are used together, consider the potential for additive effects on the QT interval.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and degarelix; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Degarelix is also associated with QT prolongation.
    Chloroquine: (Major) Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible. If coadministration is necessary, use caution.
    Chlorpromazine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include degarelix.
    Cimetidine: (Minor) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as cimetidine, should not be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Ciprofloxacin: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation, such as ciprofloxacin. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or receiving treatment with ciprofloxacin.
    Cisapride: (Severe) Degarelix can cause QT prolongation. Because of the potential for torsade pointes (TdP), use of cisapride with degarelix is contraindicated.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. Degarelix is associated with a possible risk for QT prolongation and TdP (torsade de pointes). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include clarithromycin.
    Class IA Antiarrhythmics: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Other agents associated with a possible risk for QT prolongation and torsade de pointes (TdP) include degarelix.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Conjugated Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Conjugated Estrogens; Bazedoxifene: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Conjugated Estrogens; Medroxyprogesterone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with degarelix. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation; QTc prolongation has also been reported with the use of degarelix.
    Cyclobenzaprine: (Major) Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes (TdP), particularly in the event of acute overdose. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with cyclobenzaprine include degarelix.
    Danazol: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include degarelix.
    Dasatinib: (Major) In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with dasatinib include degarelix.
    Daunorubicin: (Major) Acute cardiotoxicity can occur during the administration of daunorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with daunorubicin include degarelix.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Deutetrabenazine: (Major) For patients taking a deutetrabenazine dosage more than 24 mg/day with degarelix, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. QTc prolongation has been reported with the use of degarelix.
    Dextromethorphan; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Dextromethorphan; Quinidine: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Dienogest; Estradiol valerate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Diethylstilbestrol, DES: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Disopyramide: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Dofetilide: (Severe) Degarelix can cause QT prolongation. Because of the potential for torsade pointes (TdP), use of dofetilide with degarelix is contraindicated.
    Dolasetron: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with dolasetron include degarelix.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include degarelix.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include degarelix.
    Doxorubicin: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dronedarone: (Severe) Degarelix can cause QT prolongation. Because of the potential for torsade pointes (TdP), use of dronedarone with degarelix is contraindicated.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include degarelix.
    Drospirenone; Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Drospirenone; Ethinyl Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Efavirenz: (Major) Although data are limited, coadministration of efavirenz and degarelix may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of both drugs. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and degarelix may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of both drugs. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include degarelix.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with rilpivirine include degarelix.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with rilpivirine include degarelix.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Epirubicin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering degarelix with epirubicin. Voriconazole has been associated with prolongation of the QT interval. Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eribulin: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include eribulin.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with erythromycin include degarelix.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with erythromycin include degarelix.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as degarelix, should be done with caution and close monitoring.
    Ester local anesthetics: (Major) Coadministration of degarelix and local anesthetics may result in additive QT prolongation.
    Esterified Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Esterified Estrogens; Methyltestosterone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix. (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol Cypionate; Medroxyprogesterone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Levonorgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estradiol; Norgestimate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estrogens: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Estropipate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Desogestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Etonogestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Levonorgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norelgestromin: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone Acetate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norgestimate: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ethinyl Estradiol; Norgestrel: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Ezogabine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include ezogabine.
    Fingolimod: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include degarelix.
    Flecainide: (Major) Degarelix should be used cautiously and with close monitoring with flecainide. Degarelix can cause QT prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Major) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluconazole include degarelix.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include degarelix.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include degarelix. (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like olanzapine. In addition, olanzapine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Fluoxymesterone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Fluphenazine: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like fluphenazine. In addition, fluphenazine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and degarelix. Coadminister with caution. QTc prolongation has been reported with the use of degarelix. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as degarelix. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QTc prolongation has also been reported with the use of degarelix. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gemifloxacin: (Major) Gemifloxacin may prolong the QT interval in some patients.The maximal change in the QTc interval occurs approximately 5-10 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. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with gemifloxacin include degarelix.
    Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and degarelix together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QTc prolongation hasbeen reported with the use of degarelix.
    Goserelin: (Major) Degarelix should be used cautiously and with close monitoring with goserelin. Degarelix can cause QT prolongation. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Granisetron: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with granisetron include degarelix.
    Halofantrine: (Severe) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like halofantrine.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with haloperidol include degarelix.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Minor) Drugs that cause hyperprolactinemia, such as methyldopa, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and degarelix. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. QTc prolongation has been reported with the use of degarelix.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include degarelix.
    Ibutilide: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include ibutilide.
    Idarubicin: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include degarelix.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation and TdP that should be avoided with iloperidone include degarelix. In addition, drugs that cause hyperprolactinemia, such as iloperidone, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with degarelix due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QTc prolongation has also been reported with the use of degarelix.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include degarelix.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include degarelix.
    Lapatinib: (Major) Lapatinib can prolong the QT interval. Lapatinib should be administered with caution to patients who have or may develop prolongation of QTc such as patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation. Administer lapatinib with caution in patients taking drugs with the potential to induce QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with lapatinib include degarelix.
    Lenvatinib: (Major) Lenvatinib should be used cautiously and with close monitoring with degarelix. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: (Major) It is not common for these two agents to be used together at the same time, due to duplicate effects on hormone regulation. Androgen deprivation therapy (e.g., leuprolide, degarelix) prolongs the QT interval; the risk may be increased with concurrent use.
    Leuprolide; Norethindrone: (Major) It is not common for these two agents to be used together at the same time, due to duplicate effects on hormone regulation. Androgen deprivation therapy (e.g., leuprolide, degarelix) prolongs the QT interval; the risk may be increased with concurrent use.
    Levofloxacin: (Major) Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval, including degarelix.
    Lithium: (Major) Degarelix should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation.Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Long-acting beta-agonists: (Moderate) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with degarelix include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like degarelix, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like degarelix, should be used cautiously and with close monitoring with loperamide.
    Lopinavir; Ritonavir: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include lopinavir; ritonavir. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include degarelix.
    Loxapine: (Moderate) In theory, loxapine can decrease the effects of degarelix. Degarelix is a gonadotropin releasing hormone receptor antagonist. Drugs that cause hyperprolactinemia (e.g., loxapine) should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Maprotiline: (Major) 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. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include degarelix.
    Mefloquine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include mefloquine.
    Meperidine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Mesoridazine: (Severe) Degarelix interacts with antipsychotics by different mechanisms. Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like mesoridazine. Prescribers need to weigh the potential benefits and risks of ganirelix use in patients that are taking antipsychotic drugs that can cause QT prolongation. In addition, mesoridazine causes hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Mestranol; Norethindrone: (Major) Concomitant use of estrogens with GnRH analogs is relatively contraindicated, as estrogens could counteract the therapeutic effect of GnRH analogs for various hormone-sensitive conditions. In the rare cases that these drugs are used together, close clinical monitoring for the desired clinical and hormonal response is necessary.
    Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with methadone include degarelix.
    Methyldopa: (Minor) Drugs that cause hyperprolactinemia, such as methyldopa, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Methyltestosterone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Metoclopramide: (Minor) Drugs that cause hyperprolactinemia, such as metoclopramide, should generally not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors. Monitor the patient for the proper clinical response to GnRH therapy.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include degarelix.
    Midostaurin: (Major) The concomitant use of midostaurin and degarelix may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QTc prolongation has also been reported with the use of degarelix.
    Mifepristone, RU-486: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and degarelix should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Degarelix can also cause QT prolongation.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and degarelix. Coadminister with caution. QTc prolongation has been reported with the use of degarelix. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine. The majority of reports have occurred in the setting of mirtazapine overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Moxifloxacin: (Major) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval, including degarelix.
    Nandrolone Decanoate: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Nilotinib: (Major) Coadministration of nilotinib and a drug that prolongs the QT interval is not advised; nilotinib prolongs the QT interval. If concurrent administration is unavoidable, the manufacturer of nilotinib recommends interruption of nilotinib treatment. If nilotinib must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be avoided in combination with nilotinib include degarelix.
    Norfloxacin: (Major) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with norfloxacin include degarelix.
    Octreotide: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include degarelix.
    Ofloxacin: (Major) Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ofloxacin include degarelix.
    Olanzapine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like olanzapine. In addition, olanzapine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include degarelix.
    Ondansetron: (Major) If ondansetron and degarelix must be coadministered, ECG monitoring is recommended. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. QTc prolongation has been reported with the use of degarelix.
    Osimertinib: (Major) Periodically monitor ECGs and electrolytes if coadministration of osimertinib with degarelix is necessary due to the risk of QT prolongation and torsade de pointes (TdP). Concentration-dependent QTc prolongation has been suggested at the recommended dosing of osimertinib in a pharmacokinetic/pharmacodynamic analysis. Degarelix may also prolong the QTc interval. Concomitant use may increase the risk of QT prolongation.
    Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and degarelix concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. QTc prolongation has also been reported with the use of degarelix.
    Oxandrolone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Oxymetholone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Paliperidone: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like paliperidone. In addition, paliperidone may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include degarelix.
    Pasireotide: (Major) Cautious use of pasireotide and degarelix is needed, as coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include pazopanib.
    Pentamidine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation.[ Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include pentamidine.
    Perphenazine: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like perphenazine. In addition, perphenazine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Perphenazine; Amitriptyline: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like perphenazine. In addition, perphenazine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval including degarelix.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of degarelix with pimozide is contraindicated.
    Posaconazole: (Major) Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with posaconazole include degarelix .
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include degarelix.
    Procainamide: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Prochlorperazine: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like prochlorperazine. In addition, prochlorperazine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include degarelix.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with degarelix. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval. Degarelix may also cause QT prolongation.
    Quetiapine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like quetiapine. In addition, quetiapine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Quinidine: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP). Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking class IA antiarrhythmics.
    Quinine: (Major) Concurrent use of quinine and degarelix should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Degarelix may also cause QT prolongation.
    Ranolazine: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as ranolazine. Weigh the potential benefits and risks of degarelix use in patients taking other drugs that may prolong the QT interval.
    Regadenoson: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include regadenoson.
    Reserpine: (Minor) Drugs that cause hyperprolactinemia, such as reserpine, should not be administered concomitantly with GnRH analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
    Ribociclib: (Major) Avoid coadministration of ribociclib with degarelix due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; QTc prolongation has also been reported with the use of degarelix. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with degarelix due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; QTc prolongation has also been reported with the use of degarelix. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with rilpivirine include degarelix.
    Risperidone: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like risperidone. In addition, risperidone may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include degarelix.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with romidepsin include degarelix.
    Saquinavir: (Major) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Drugs with a possible risk for QT prolongation and TdP that should avoided in combination with saquinavir include degarelix.
    Sertraline: (Major) There have been post-marketing reports of QT prolongation and Torsade de Pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sertraline include degarelix.
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with degarelix. Halogenated anesthetics can prolong the QT interval. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Short-acting beta-agonists: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with degarelix include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Solifenacin: (Major) Solifenacin should be used cautiously and with close monitoring with degarelix. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Sorafenib: (Major) Sorafenib has been associated with QT prolongation. If sorafenib and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sorafenib include: degarelix.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include degarelix.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include degarelix.
    Sunitinib: (Major) Sunitinib can prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sunitinib include degarelix.
    Tacrolimus: (Major) Tacrolimus causes QT prolongation. Other agents associated with a possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation that should be used cautiously with tacrolimus include degarelix.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen with degarelix due to an increased risk of QT prolongation. 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. QTc prolongation has been reported with the use of degarelix.
    Telavancin: (Major) Telavancin has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with telavancin include degarelix.
    Telithromycin: (Major) Telithromycin is associated with QT prolongation and torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with telithromycin include degarelix.
    Testolactone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Testosterone: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including degarelix. In addition, drugs that cause hyperprolactinemia, such as tetrabenazine, should not be administered concomitantly with gonadotropin-releasing hormone (GnRH) analogs (degarelix) since hyperprolactinemia down regulates the number of pituitary GnRH receptors.
    Thioridazine: (Severe) Degarelix can cause QT prolongation. Because of the potential for torsade pointes (TdP), use of thioridazine with degarelix is contraindicated.
    Tizanidine: (Major) Both tizanidine and degarelix can cause QT prolongation. Tizanidine should be used cautiously and with close monitoring with degarelix. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with degarelix. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Degarelix can also cause QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other QT prolonging drugs.
    Toremifene: (Major) Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with toremifene include degarelix.
    Trazodone: (Major) Degarelix can cause QT prolongation and should be avoided in combination with trazodone. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Tricyclic antidepressants: (Minor) Tricyclic antidepressants (TCAs) should be used cautiously and with close monitoring with degarelix. Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval.
    Trifluoperazine: (Minor) Since degarelix can cause QT prolongation, degarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation like trifluoperazine. In addition, trifluoperazine may cause hyperprolactinemia and should not generally be administered concomitantly with degarelix, as hyperprolactinemia downregulates the number of pituitary gonadotropin-releasing hormone receptors.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include degarelix.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; QTc prolongation has also been reported with the use of degarelix. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vardenafil include degarelix.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vemurafenib include degarelix.
    Venlafaxine: (Major) Venlafaxine administration is associated with a possible risk of QT prolongation; torsades de pointes (TdP) has reported with post-marketing use. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with venlafaxine include degarelix.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with degarelix. Prescribers need to weigh the benefits and risks prior to coadministration. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Degarelix can also cause QT prolongation.
    Vorinostat: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include vorinostat.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including degarelix.

    PREGNANCY AND LACTATION

    Pregnancy

    Degarelix is not indicated for use in females, and is contraindicated for use in females of childbearing age. According to the manufacturer degarelix is a pregnancy category X drug and should not be used in women who are pregnant or may become pregnant. Embryo and fetal death and abortion occurred when degarelix (0.02% of the clinical loading dose) was administered to rabbits during organogenesis. In rats, degarelix (0.036% of the clinical loading dose) given during organogenesis resulted in an increase in post implantation loss and a decrease in the number of live fetuses. If degarelix is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential risk to the fetus.

    Degarelix is not indicated for use in females. It is unknown if degarelix is excreted in human milk. As a result of the potential for serious adverse events in nursing infants exposed to degarelix, according to the manufacturer, a decision should be made whether to discontinue breast-feeding or discontinue the drug.

    MECHANISM OF ACTION

    Degarelix is a gonadotropin releasing hormone (GnRH) receptor antagonist. Degarelix binds reversibly to the anterior pituitary GnRH receptor thereby reducing luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion. This results in an immediate and sustained decrease in the testosterone concentration without the initial stimulation of the hypothalamic-pituitary-gonadal axis. Testosterone suppression to castrate concentrations (0.5 ng/mL) is achieved within 1—3 days of administration.

    PHARMACOKINETICS

    Degarelix is administered by subcutaneous (SC) injection. Degarelix is distributed in total body water and has an estimated plasma protein binding of approximately 90%. Metabolism of degarelix is via peptide hydrolysis. In vitro studies indicate degarelix is not a substrate, inducer, or inhibitor of the CYP450 or p-glycoprotein transporter system. Degarelix is mainly eliminated via the hepatobiliary system (70—80%) with the remaining dose excreted unchanged in the urine (20—30%).

    Subcutaneous Route

    After subcutanous administration, a depot is formed from which degarelix is slowly released into circulation reaching a peak plasma concentration within 2 days. A median terminal half life of 53 days for degarelix is a result of the prolonged release from the depot formed during subcutaneous administration.
    Testosterone suppression to castrate concentrations (0.5 ng/mL) is achieved within 1—3 days of administration. In a randomized, open-label study, patients with prostate cancer were randomized to receive either degarelix or leuprolide. Patients in the degarelix group received a starting dose of 240 mg SC monthly for 1 month, then a maintenance dose of either 80 mg or 160 mg subcutaneously monthly; patients in the leuprolide group received 7.5 mg leuprolide IM monthly. By day 3, the median testosterone concentrations were < 0.5 ng/mL in 96.1% and 95.5% of patients in the degarelix 240/80 and 240/160 mg groups, respectively. Conversely, in patients receiving leuprolide, the median testosterone concentration increased by 65% from baseline at day 3 (median testosterone concentration = 6.30 ng/mL; p < 0.001). In the leuprolide group, the median testosterone concentrations were > 0.5 ng/mL until the measurements on day 28; from this point forward, however, testosterone concentrations were suppressed in all patients in all treatment groups. The median testosterone concentrations (from 28 to 364 days) were 0.082 ng/mL, 0.088 ng/mL, and 0.078 ng/mL in the degarelix 240/80 mg, degarelix 240/160 mg, and leuprolide groups, respectively.