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  • CLASSES

    Cytostatic Gonadotropin-Releasing Hormone Agonists
    Gonadotropin-Releasing Hormone Agonists

    DEA CLASS

    Rx

    DESCRIPTION

    Agonist analog of gonadotropin-releasing hormone (GnRH)
    Used for the palliative treatment of advanced prostate cancer and the treatment of central precocious puberty
    Depression, including rare reports of suicidal ideation and attempt, has been reported with GnRH agonists in children treated for CPP

    COMMON BRAND NAMES

    Trelstar, Triptodur

    HOW SUPPLIED

    Trelstar Intramuscular Inj Pwd F/Susp: 3.75mg, 11.25mg, 22.5mg
    Triptodur Intramuscular Inj Pwd F/Susp ER: 22.5mg

    DOSAGE & INDICATIONS

    For the palliative treatment of advanced prostate cancer.
    Intramuscular dosage (Trelstar)
    Adult males

    3.75 mg IM every 4 weeks, as a single injection in either buttock. Due to different release characteristics, the dosage strengths are not additive and must be selected based on the desired dosing schedule. In a randomized, active control trial, castrate levels of serum testosterone (1.735 nmol/L, equivalent to 50 ng/dL) were achieved by day 29 in 91.2% of men with advanced prostate cancer treated with triptorelin 3.375 mg once monthly (n = 137); castrate levels were achieved by day 57 in 97.7% of these patients. Maintenance of castration levels of serum testosterone through day 253 was found in 96.2% of patients receiving triptorelin 3.375 mg once monthly. Serum LH levels of 1 IU/L or less were found in 98.4% of patients at 2 hours after dosing on day 85, indicating desensitization of the pituitary gonadotraph receptors.[45411]

    Intramuscular dosage (Trelstar)
    Adults

    11.25 mg IM every 12 weeks, as a single injection in either buttock. Due to different release characteristics, the dosage strengths are not additive and must be selected based on the desired dosing schedule. In a randomized, active control trial, castrate levels of serum testosterone (1.735 nmol/L, equivalent to 50 ng/dL) were achieved by day 29 in 97.7% of men with advanced prostate cancer treated with triptorelin 11.25 mg every 3 months (n = 174). Maintenance of castration levels of serum testosterone through day 253 was found in 94.4% of these patients.

    Intramuscular dosage (Trelstar)
    Adults

    22.5 mg IM every 24 weeks, as a single injection in either buttock. Due to different release characteristics, the dosage strengths are not additive and must be selected based on the desired dosing schedule. In a noncomparative trial, castrate levels of serum testosterone (1.735 nmol/L, equivalent to 50 ng/dL) were achieved by day 29 in 97.5% of men with advanced prostate cancer treated with triptorelin 22.5 mg every 6 months (n = 120). Maintenance of castration levels of serum testosterone through day 337 was found in 93.3% of these patients.

    For the treatment of central precocious puberty.
    Intramuscular dosage (i.e., Triptodur)
    Children and Adolescents 2 to 17 years

    22.5 mg IM once every 24 weeks. Discontinue at the appropriate age of onset of puberty at the discretion of the physician.

    For the treatment of premenopausal women with hormone-sensitive advanced breast cancer†.
    Intramuscular dosage (e.g., Trelstar)
    Adult females†

    3.75 mg IM once monthly until disease progression. In a study of 27 premenopausal women with hormone-sensitive, previously untreated metastatic breast cancer, triptorelin produced an overall response rate of 70% (complete response 18%; partial response 52%). The median time to progression was 12 months.

    For pituitary downregulation in women undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF) or other assisted reproductive technology (ART) for the treatment of infertility†.
    Intramuscular dosage (e.g., triptorelin acetate depot injection such as Decapeptyl injection, not available in U.S.)
    Adult females

    Safety and efficacy not established; not FDA-approved. A common regimen is 3.75 mg IM triptorelin acetate depot single-dose given 15 days prior to initiation of ovarian stimulation therapy, but other regimens have been reported.

    For the treatment of endometriosis†.
    Intramuscular dosage (e.g., triptorelin acetate or triptorelin embonate injection, these dosage forms not available in the U.S.)
    Adult females

    Safety and efficacy not established; not FDA-approved. 3.75 mg IM depot once monthly for 3 to 6 months has been studied. In one trial, the extent and area of endometrial lesions decreased 45% to 50% and pain symptoms were significantly improved in patients treated with triptorelin. Clinical guidelines/studies suggest the addition of hormonal add-back therapy (e.g., estrogens and/or progestins) to triptorelin as an effective means of reducing the bone mineral loss/other side effects that occur with triptorelin therapy alone.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Maximum dose is dependent on product strength; give no more than the 3.75 mg product IM every 4 weeks, the 11.25 mg product IM every 12 weeks, and the 22.5 mg product IM every 24 weeks.

    Geriatric

    Maximum dose is dependent on product strength; give no more than the 3.75 mg product IM every 4 weeks, the 11.25 mg product IM every 12 weeks, and the 22.5 mg product IM every 24 weeks.

    Adolescents

    22.5 mg IM every 24 weeks.

    Children

    2 to 12 years: 22.5 mg IM every 24 weeks.
    1 year: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 2
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Triptorelin is for intramuscular use only; do not administer intravenously.
     
    Triptorelin pamoate (Trelstar) Mixject:
     
    Reconstitution:
    Place sealed tray on a clean, flat surface that is covered with a sterile pad or cloth.
    Peel the cover away from the tray and remove the Mixject components and the vial of triptorelin. Remove the Flip-Off button from the top of the vial.
    Peel the cover away from the blister pack containing the vial adaptor, but do not remove the vial adapter from the blister pack. Place the blister pack CONTAINING THE VIAL ADAPTER firmly on the vial top, piercing the vial. Push gently until it snaps into place, and then remove the blister pack from the vial adapter.
    Screw the plunger rod into the barrel end of the syringe and remove the cap from the syringe barrel.
    Screw the syringe clockwise into the opening on the side of the vial adapter to connect them; twist until the syringe stops to ensure a tight connection. The syringe contains Sterile Water for Injection, USP; no other diluent should be used.
    While holding the vial, push the plunger rod to transfer the diluent from the pre-filled syringe into the vial; do not release the plunger rod.
    Keeping the plunger rod depressed, gently swirl the vial so the diluent rinses the sides of the vial; the suspension should have a milky appearance. To avoid separation of the suspension, proceed immediately to the next steps of reconstitution.
    Invert the Mixject system so that the vial is at the top. Grasping the Mixject system firmly by the syringe, pull back the plunger rod slowly to draw the reconstituted triptorelin into the syringe.
    After returning the vial to its upright position, disconnect the vial adapter and vial from the Mixject syringe by turning the plastic cap of the vial adapter clockwise. Grasp only the plastic cap when removing.
    Lift the safety cover and remove the clear plastic needle shield. The syringe containing triptorelin is now ready for administration.
    After administration, activate the safety mechanism by pushing it forward over the needle until you hear or feel it click. Immediately discard the syringe assembly after a single use into a sharps container.[45411]
     
    Intramuscular Injection (Trelstar):
    Administer as a single intramuscular injection into either buttock, immediately after reconstitution. Periodically alternate injection sites.[45411]
     
    Triptorelin (Triptodur)
    Reconstitution:
    Reconstitute with sterile water only; do not use any other diluent.
    Screw the plunger rod into the barrel end of the prefilled sterile water diluent syringe and remove the cap from the syringe barrel.
    Firmly attach one of the 21-gauge safety needles onto the prefilled sterile water diluent syringe; this 21-gauge needle will only be used for reconstitution of the product.
    Pull back on the safety cover towards the syringe and away from the 21-gauge needle before pulling the clear needle shied off.
    Insert the 21-gauge needle into the vial to inject the sterile water diluent.
    Without releasing the plunger rod, gently swirl the vial ensuring the diluent rinses the sides of the vial. The suspension will appear milky.
    Withdraw the entire contents of the vial into the syringe. Push the safety cover forward toward the needle until it locks. Remove the first 21-gauge needle and discard it. Attach a second sterile needle onto the syringe and pull back the safety cover towards the syringe.
    After priming the needle, administer the suspension immediately if it appears milky and homogenous without visible aggregates or precipitates.[62072]
     
    Intramuscular injection (Triptodur):
    Inject the patient preferably in either buttock or thigh using the entire contents of the syringe.
    Injection of the suspension should be relatively rapid and performed in a steady and uninterrupted manner to avoid any potential blockage of the needle.
    After administering the injection, immediately activate the safety cover and discard into a sharps container.[62072]

    STORAGE

    Trelstar:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Trelstar Depot:
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Trelstar LA:
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Triptodur:
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Gonadotropin-Releasing Hormone (GnRH) analogs hypersensitivity

    Triptorelin is contraindicated in patients with hypersensitivity to triptorelin, GnRH, or with Gonadotropin-Releasing Hormone (GnRH) Analogs hypersensitivity. Anaphylactic shock, hypersensitivity, and angioedema have been reported. Immediately discontinue triptorelin immediately in the event of a hypersensitivity reaction and administer the appropriate supportive care measures.

    Renal impairment, spinal cord compression, urinary tract obstruction

    Due to transient increases in testosterone levels, triptorelin may cause the onset or worsening of prostate cancer symptoms (flare) such as bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction during the first weeks of therapy. Patients with urinary tract obstruction or metastatic vertebral lesions should be monitored carefully for signs of renal impairment or spinal cord compression, respectively, during initial triptorelin treatment. If spinal cord compression or renal impairment develops, implement standard treatment; in extreme cases, an immediate orchiectomy should be considered.[45411] During initial therapy for central precocious puberty, gonadotropins and sex steroids may rise above baseline because of a transient stimulatory effect of the drug. Therefore, a transient increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during the first weeks of therapy or after subsequent doses.[62072]

    Pituitary insufficiency

    Since triptorelin 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.  The effects of triptorelin on pituitary and gonadal function are expected to disappear within 6 to 12 months after treatment discontinuation.

    Dysfunctional uterine bleeding, menstruation, vaginal bleeding

    As with other GnRH analog treatments, triptorelin therapy will interrupt menstruation; women who continue to menstruate or who experience breakthrough bleeding while receiving triptorelin should notify their physician. The drug should not be administered to women with dysfunctional uterine bleeding or undiagnosed vaginal bleeding. Triptorelin has been used off-label to treat various conditions in women, but is not FDA-approved for use in female patients after the appropriate age of onset of puberty. When used for central precocious puberty, vaginal bleeding may occur during the first weeks of treatment, but should resolve by the second month after administration.

    Osteoporosis

    Use triptorelin with caution in patients with osteoporosis. GnRH analog therapy increases the risk of reduced bone mineral density in men as well as women. The addition of hormone replacement therapy (e.g., estrogens) to triptorelin therapy for endometriosis or uterine fibroids may be effective in reducing the bone mineral loss in selected women.

    Diabetes mellitus

    Use triptorelin with caution in patients with pre-existing diabetes mellitus. Hyperglycemia and an increased risk of developing diabetes mellitus have been reported in men receiving GnRH agonists; glucose control may worsen in patients already diagnosed with diabetes. Periodically monitor blood glucose and/or glycosylated hemoglobin (HbA1c) in all patients; manage hyperglycemia according to current practice standards.

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

    Androgen deprivation therapy may cause QT prolongation. Use triptorelin with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Cardiac disease

    Use triptorelin with caution in patients with a history of cardiac disease. An increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of GnRH agonists in men. The risk appears low based on reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining the most appropriate course of treatment. Monitor patients for signs and symptoms suggestive of cardiovascular disease, and manage any developments according to current clinical standards.[45411]

    Brain tumor, cerebrovascular disease, seizure disorder

    Use triptorelin with caution in patients with a preexisting seizure disorder. Seizures have been reported during postmarketing surveillance in patients with a history of epilepsy, cerebrovascular disease, central nervous system anomalies or brain tumor, and patients on concomitant medications that have been associated with seizures. Seizures have also been reported in patients without any risk factors.

    Depression, psychiatric event, suicidal ideation

    Patients should be observed for a potential psychiatric event or worsening of psychiatric symptoms during treatment with triptorelin. During postmarketing experience, emotional lability, such as crying, irritability, impatience, anger, and aggression were reported. Depression, including rare reports of suicidal ideation and attempt, were reported in children treated with GnRH agonists for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Counsel patients on the possibility of development or worsening of depression during triptorelin receipt, and to report any unusual changes in moods or behavior.

    Infertility

    Although there are no data regarding the effect of triptorelin on human fertility, male infertility has may occur based on the mechanism of action of triptorelin. In animal studies, triptorelin had no effect on the fertility or general reproductive function of female rats. No studies were conducted to assess the effect of triptorelin on male fertility.

    Pregnancy

    Triptorelin (Triptodur) is contraindicated in pregnancy. Triptorelin (Trelstar) is not indicated for treatment in females. Although there are no adequately controlled studies in pregnant women, triptorelin can cause fetal harm when administered during pregnancy based on its mechanism of action and animal studies. Expected hormonal changes that occur with triptorelin treatment increase the risk for pregnancy loss. Women who are pregnant or who become pregnant while receiving triptorelin should be apprised of the potential hazard to the fetus. Pregnant rats who received triptorelin during organogenesis at exposures equivalent to 0.2, 0.8, and 8 times the estimated human dose based on BSA demonstrated maternal toxicity and embryo-fetal toxicities, including pre-implantation loss, increased resorption, and reduced mean number of viable fetuses at the high dose. Teratogenic effects were not observed.[45411] [62072]

    Breast-feeding

    It is not known if triptorelin is excreted in human milk, the effects of the drug on the breast-feeding infant, or on milk production. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from the pharmacology of triptorelin, a decision should be made to either discontinue breast-feeding or discontinue the drug taking into account the importance of the drug to the mother.

    Laboratory test interference

    Clinicians should be aware that a laboratory test interference may occur with use of triptorelin. Chronic or continuous administration of triptorelin in therapeutic doses results in suppression of the pituitary-gonadal axis. Diagnostic tests of the pituitary-gonadal function conducted during treatment and after cessation of therapy may therefore be misleading.

    Pseudotumor cerebri

    Gonadotropin releasing hormone (GnRH) agonists, including triptorelin, have been associated with cases of pseudotumor cerebri (idiopathic intracranial hypertension) in pediatric patients. Monitor patients for signs and symptoms including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

    ADVERSE REACTIONS

    Severe

    pituitary apoplexy / Early / 0-1.0
    suicidal ideation / Delayed / 0-1.0
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    visual impairment / Early / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    stroke / Early / Incidence not known
    seizures / Delayed / Incidence not known
    spinal cord compression / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known

    Moderate

    hypertension / Early / 0.8-14.2
    bone pain / Delayed / 12.1-13.2
    vaginal bleeding / Delayed / 7.7-7.7
    peripheral edema / Delayed / 1.1-6.3
    urinary retention / Early / 1.1-5.0
    dysuria / Early / 0-4.6
    edema / Delayed / 2.3-2.3
    constipation / Delayed / 0-1.7
    chest pain (unspecified) / Early / 0-1.7
    conjunctivitis / Delayed / 0-1.1
    dyspnea / Early / 0-1.1
    anemia / Delayed / 1.4
    elevated hepatic enzymes / Delayed / 1.1
    osteoporosis / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    tumor flare / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    interstitial lung disease / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 3.6-45.0
    infection / Delayed / 1.1-15.8
    influenza / Delayed / 4.5-15.8
    headache / Early / 1.7-13.6
    pharyngitis / Delayed / 1.1-13.6
    back pain / Delayed / 0.8-10.8
    arthralgia / Delayed / 0.8-7.5
    cough / Delayed / 1.7-6.8
    insomnia / Early / 0.8-5.0
    sinusitis / Delayed / 0-4.5
    dizziness / Early / 1.4-2.9
    nausea / Early / 0-2.9
    fatigue / Early / 2.1-2.3
    pruritus / Rapid / 0-2.3
    emotional lability / Early / 1.4-2.3
    anxiety / Delayed / 2.3-2.3
    vomiting / Early / 0-2.1
    dyspepsia / Early / 0-1.7
    anorexia / Delayed / 0-1.7
    rash / Early / 0-1.7
    diarrhea / Early / 1.1-1.4
    myalgia / Early / 0-1.1
    ocular pain / Early / 0-1.1
    abdominal pain / Early / 0-1.1
    asthenia / Delayed / 0-1.1
    hot flashes / Early / 10.0
    urticaria / Rapid / Incidence not known
    irritability / Delayed / Incidence not known
    weakness / Early / Incidence not known

    DRUG INTERACTIONS

    Alfuzosin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving alfuzosin. Androgen deprivation therapy may prolong the QT/QTc interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner.
    Amiodarone: (Major) Concomitant use of triptorelin and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with triptorelin. Amisulpride causes dose- and concentration- dependent QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Amoxapine: (Major) Avoid coadministration of triptorelin with amoxapine due to the risk of reduced efficacy of triptorelin. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Anagrelide: (Major) Do not use anagrelide with triptorelin due to the risk of QT prolongation. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Androgen deprivation therapy (e.g., triptorelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Androgens: (Major) Gonadotropin releasing hormone (GnRH) agonists (i.e.,triptorelin) inhibit steroidogenesis, therefore the concomitant use of these agents with androgens may counteract this therapeutic effect. Avoid concurrent use of androgens with GnRH agonists.
    Apomorphine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Aripiprazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving aripiprazole. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with triptorelin; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with triptorelin if possible due to the risk of QT prolongation. Consider ECG monitoring if triptorelin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. (Major) Avoid coadministration of lumefantrine with triptorelin if possible due to the risk of QT prolongation. Consider ECG monitoring if triptorelin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Asenapine: (Major) Avoid coadministration of triptorelin with asenapine due to the risk of reduced efficacy of triptorelin as well as the risk of QT prolongation. Asenapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Additionally, asenapine has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Atomoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving atomoxetine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval has also occurred during therapeutic use of atomoxetine and following overdose.
    Azithromycin: (Major) Concomitant use of triptorelin and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bedaquiline: (Major) Frequently monitor ECGs for QT prolongation if coadministration of bedaquiline with triptorelin is necessary. Bedaquiline has been reported to prolong the QT interval; coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Brexpiprazole: (Major) Avoid coadministration of triptorelin with brexpiprazole due to the risk of reduced efficacy of triptorelin. Brexpiprazole can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Buprenorphine: (Major) Concomitant use of triptorelin and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Buprenorphine; Naloxone: (Major) Concomitant use of triptorelin and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Cabotegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Cariprazine: (Major) Avoid coadministration of triptorelin with cariprazine due to the risk of reduced efficacy of triptorelin. Cariprazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Ceritinib: (Major) Avoid coadministration of ceritinib with triptorelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Chloroquine: (Major) Avoid coadministration of chloroquine with triptorelin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT interval.
    Chlorpromazine: (Major) Avoid coadministration of triptorelin with chlorpromazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Chlorpromazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Additionally, chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Ciprofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving ciprofloxacin. Androgen deprivation therapy may prolong the QT/QTc interval. Rare cases of QT prolongation and torsade de pointes (TdP) have also been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with cisapride is contraindicated. Prolongation of the QT interval and ventricular arrhythmias, including TdP) and death, have been reported with cisapride. Androgen deprivation therapy (e.g., triptorelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Citalopram: (Major) Concomitant use of triptorelin and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Clofazimine: (Moderate) Concomitant use of clofazimine and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Clozapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving clozapine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Codeine; Promethazine: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Crizotinib: (Major) Avoid coadministration of crizotinib with triptorelin due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Androgen deprivation therapy (e.g., triptorelin) also prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    Dasatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Desflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Deutetrabenazine: (Major) Avoid coadministration of triptorelin with deutetrabenazine due to the risk of reduced efficacy of triptorelin. Deutetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin-releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Disopyramide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving disopyramide. Androgen deprivation therapy may prolong the QT/QTc interval. Disopyramide administration is also associated with QT prolongation and torsade de pointes (TdP).
    Dofetilide: (Major) Coadministration of dofetilide and triptorelin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Dolasetron: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Donepezil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving donepezil as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Donepezil; Memantine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving donepezil as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Androgen deprivation therapy (e.g., triptorelin) may also prolong the QT/QTc interval.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as triptorelin. If coadministration is unavoidable, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Efavirenz: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving efavirenz as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QTc interval has also been observed with the use of efavirenz.
    Eliglustat: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving eliglustat. Androgen deprivation therapy may prolong the QT/QTc interval. Eliglustat is also predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Encorafenib: (Major) Avoid coadministration of encorafenib and triptorelin due to the risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Entrectinib: (Major) Avoid coadministration of entrectinib with triptorelin due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Eribulin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with triptorelin is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Erythromycin: (Major) Concomitant use of triptorelin and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Escitalopram: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving escitalopram. Androgen deprivation therapy may prolong the QT/QTc interval. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
    Fingolimod: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving fingolimod as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Concomitant use of triptorelin and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fluconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving fluconazole as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Fluconazole has also been associated with QT prolongation as well as rare cases of torsade de pointes (TdP).
    Fluoxetine: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risk of QT prolongation in patients receiving fluoxetine. QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Fluphenazine: (Major) Avoid coadministration of triptorelin with fluphenazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Fluphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Additionally, androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Fluvoxamine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving fluvoxamine. Androgen deprivation therapy may prolong the QT/QTc interval. Prolongation of the QT interval and torsade de pointes (TdP) has also been reported during fluvoxamine post-marketing use.
    Foscarnet: (Major) Avoid coadministration of foscarnet with triptorelin due to the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet.
    Fostemsavir: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents like fostemsavir. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Gemifloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving gemifloxacin as concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Gemtuzumab Ozogamicin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and triptorelin due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
    Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and triptorelin is necessary. Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Gilteritinib has also been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with triptorelin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Granisetron: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
    Halogenated Anesthetics: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Haloperidol: (Major) Avoid coadministration of triptorelin with haloperidol due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Avoid coadministration of triptorelin with methyldopa due to the risk of reduced efficacy of triptorelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Hydroxychloroquine: (Major) Concomitant use of triptorelin and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with triptorelin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Androgen deprivation therapy may prolong the QT/QTc interval.
    Ibutilide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Iloperidone: (Major) Avoid coadministration of triptorelin with iloperidone due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Iloperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Iloperidone has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with triptorelin due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Isoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Itraconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving itraconazole as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with triptorelin if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Androgen deprivation therapy (i.e., triptorelin) also may prolong the QT/QTc interval.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e. triptorelin) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Lapatinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving lapatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
    Lefamulin: (Major) Avoid coadministration of lefamulin with triptorelin as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with triptorelin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Levofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving levofloxacin as concurrent use may increase the risk for QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Levofloxacin has also been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and androgen deprivation therapy (i.e. triptorelin) due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Lithium: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving lithium. Lithium has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Lofexidine: (Major) ECG monitoring is recommended if lofexidine is coadministered with triptorelin due to the potential for additive QT prolongation. Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Loperamide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Loperamide; Simethicone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with triptorelin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Lorcaserin: (Major) Avoid coadministration of triptorelin with lorcaserin due to the risk of reduced efficacy of triptorelin. Lorcaserin can cause hyperprolactinemia, which reduces the number of pituitary GnRH receptors; triptorelin is a GnRH analog.
    Loxapine: (Major) Avoid coadministration of triptorelin with loxapine due to the risk of reduced efficacy of triptorelin. Loxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as triptorelin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Maprotiline: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mefloquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
    Meperidine; Promethazine: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Methadone: (Major) Coadministration of methadone with triptorelin should be undertaken with extreme caution and a careful assessment of the benefits of therapy versus the risks of QT prolongation. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Androgen deprivation therapy may prolong the QT/QTc interval.
    Methyldopa: (Major) Avoid coadministration of triptorelin with methyldopa due to the risk of reduced efficacy of triptorelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Metoclopramide: (Major) Avoid coadministration of triptorelin with metoclopramide due to the risk of reduced efficacy of triptorelin. Metoclopramide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Metronidazole: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Midostaurin: (Major) Consider periodic monitoring of EGCs for QT prolongation if coadministration of triptorelin and midostaurin is necessary. Prolongation of the QT interval was reported in patients who received midostaurin in clinical trials. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Mifepristone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving mifepristone. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Mifepristone has been associated with dose-dependent prolongation of the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Mirtazapine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving mirtazapine. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported in postmarketing experience, primarily in overdose or in patients with other risk factors for QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Mobocertinib: (Major) Concomitant use of mobocertinib and androgen deprivation therapy (i.e. triptorelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Molindone: (Major) Avoid coadministration of triptorelin with molindone due to the risk of reduced efficacy of triptorelin. Molindone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Moxifloxacin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving moxifloxacin. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, torsade de pointes (TdP) has been reported during postmarketing surveillance of moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Nilotinib: (Major) Avoid administration of nilotinib with triptorelin due to the risk of QT interval prolongation. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Octreotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Androgen deprivation therapy may prolong the QT/QTc interval.
    Ofloxacin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving ofloxacin as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Ofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin.
    Olanzapine: (Major) Avoid coadministration of triptorelin with olanzapine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Olanzapine; Fluoxetine: (Major) Avoid coadministration of triptorelin with olanzapine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risk of QT prolongation in patients receiving fluoxetine. QT prolongation and TdP have been reported in patients treated with fluoxetine. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Olanzapine; Samidorphan: (Major) Avoid coadministration of triptorelin with olanzapine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Olanzapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Ondansetron: (Major) Concomitant use of triptorelin and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
    Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with triptorelin. Osilodrostat is associated with dose-dependent QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Osimertinib: (Major) Avoid coadministration of triptorelin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Oxaliplatin: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving oxaliplatin concomitantly with triptorelin; correct electrolyte abnormalities prior to administration of oxaliplatin. Prolongation of the QT interval and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking triptorelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Pacritinib: (Major) Concomitant use of pacritinib and androgen deprivation therapy (i.e. triptorelin) increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Avoid coadministration of triptorelin with paliperidone due to the risk of reduced efficacy of triptorelin and the risk of QT prolongation. Paliperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Panobinostat: (Major) Coadministration of panobinostat with triptorelin is not recommended due to the risk of QT prolongation. Prolongation of the QT interval has been reported with panobinostat treatment. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Pasireotide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving pasireotide as concurrent use may increase the risk of QT prolongation. Prolongation of the QT interval has occurred with pasireotide at therapeutic and supra-therapeutic doses. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Pazopanib: (Major) Coadministration of pazopanib and triptorelin is not advised due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Pentamidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving pentamidine. Systemic pentamidine has been associated with QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval.
    Perphenazine: (Major) Avoid coadministration of triptorelin with perphenazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Perphenazine; Amitriptyline: (Major) Avoid coadministration of triptorelin with perphenazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Perphenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Pimavanserin: (Major) Coadministration of pimavanserin with triptorelin should generally be avoided due to the risk of QT prolongation. Pimavanserin may cause QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with pimozide is contraindicated; the efficacy of triptorelin may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Pitolisant: (Major) Avoid coadministration of pitolisant with triptorelin as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking triptorelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Posaconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving posaconazole as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Primaquine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has the potential to cause QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Procainamide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Prochlorperazine: (Major) Avoid coadministration of triptorelin with prochlorperazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Prochlorperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Promethazine: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Promethazine; Dextromethorphan: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Promethazine; Phenylephrine: (Major) Concomitant use of triptorelin and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Propafenone: (Major) Concomitant use of triptorelin and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quetiapine: (Major) Concomitant use of triptorelin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quinidine: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving quinidine. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Quinine: (Major) Avoid coadministration of quinine with triptorelin due to the risk of QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Ramelteon: (Major) Avoid coadministration of triptorelin with ramelteon due to the risk of reduced efficacy of triptorelin. Ramelteon can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Ranolazine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving ranolazine as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Androgen deprivation therapy may prolong the QT/QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Reserpine: (Major) Avoid coadministration of triptorelin with reserpine due to the risk of reduced efficacy of triptorelin. Reserpine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Ribociclib: (Major) Avoid coadministration of ribociclib with triptorelin due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with triptorelin due to the risk of QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ribociclib-related ECG changes typically occurred within the first four weeks of treatment and were reversible with dose interruption. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Rilpivirine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Risperidone: (Major) Avoid coadministration of triptorelin with risperidone due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Romidepsin: (Moderate) Monitor ECGs for QT prolongation and monitor electrolytes at baseline and periodically during treatment if coadministration of romidepsin with triptorelin is necessary as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Saquinavir: (Major) Avoid coadministration of saquinavir with triptorelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, perform a baseline ECG prior to initiation of therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with triptorelin is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Sertraline: (Moderate) Consider whether the benefits of triptorelin therapy outweigh the potential risk of QT prolongation in patients receiving sertraline. If use together is necessary, use caution and monitor patients for QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving triptorelin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Solifenacin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval; torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Sorafenib: (Major) Avoid coadministration of sorafenib with triptorelin due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Sotalol: (Major) Concomitant use of triptorelin and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sunitinib: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with triptorelin. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Tamoxifen: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving tamoxifen. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses; rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Androgen deprivation therapy may prolong the QT/QTc interval.
    Telavancin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving telavancin as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Telithromycin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving telithromycin as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may prolong the QT/QTc interval.
    Tetrabenazine: (Major) Avoid coadministration of triptorelin with tetrabenazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Tetrabenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Tetrabenazine also causes a small increase in the corrected QT interval (QTc). Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with thioridazine is contraindicated; the efficacy of triptorelin may also be reduced. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Thioridazine can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Thiothixene: (Major) Avoid coadministration of triptorelin with thiothixene due to the risk of reduced efficacy of triptorelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Tolterodine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Toremifene: (Major) Avoid coadministration of triptorelin with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Trandolapril; Verapamil: (Major) Avoid coadministration of triptorelin with verapamil due to the risk of reduced efficacy of triptorelin. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Trazodone: (Major) Concomitant use of triptorelin and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Triclabendazole: (Moderate) Concomitant use of triclabendazole and androgen deprivation therapy (i.e. triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Trifluoperazine: (Major) Avoid coadministration of triptorelin with trifluoperazine due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Trifluoperazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Trifluoperazine is also associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Valbenazine: (Major) Avoid concurrent use of triptorelin with valbenazine due to the risk of reduced efficacy of triptorelin. Valbenazine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Vandetanib: (Major) Avoid coadministration of vandetanib with triptorelin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Vardenafil: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving vardenafil as concurrent use may increase the risk of QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Vemurafenib: (Major) Closely monitor ECGs for QT prolongation if coadministration of vemurafenib with triptorelin is necessary. Vemurafenib has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Venlafaxine: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Verapamil: (Major) Avoid coadministration of triptorelin with verapamil due to the risk of reduced efficacy of triptorelin. Verapamil can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
    Voclosporin: (Moderate) Concomitant use of voclosporin and triptorelin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation t supratherapeutic doses. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Androgen deprivation therapy may also prolong the QT/QTc interval.
    Voriconazole: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving voriconazole as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Vorinostat: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
    Ziprasidone: (Major) Concomitant use of ziprasidone and triptorelin should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.

    PREGNANCY AND LACTATION

    Pregnancy

    Triptorelin (Triptodur) is contraindicated in pregnancy. Triptorelin (Trelstar) is not indicated for treatment in females. Although there are no adequately controlled studies in pregnant women, triptorelin can cause fetal harm when administered during pregnancy based on its mechanism of action and animal studies. Expected hormonal changes that occur with triptorelin treatment increase the risk for pregnancy loss. Women who are pregnant or who become pregnant while receiving triptorelin should be apprised of the potential hazard to the fetus. Pregnant rats who received triptorelin during organogenesis at exposures equivalent to 0.2, 0.8, and 8 times the estimated human dose based on BSA demonstrated maternal toxicity and embryo-fetal toxicities, including pre-implantation loss, increased resorption, and reduced mean number of viable fetuses at the high dose. Teratogenic effects were not observed.[45411] [62072]

    It is not known if triptorelin is excreted in human milk, the effects of the drug on the breast-feeding infant, or on milk production. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from the pharmacology of triptorelin, a decision should be made to either discontinue breast-feeding or discontinue the drug taking into account the importance of the drug to the mother.

    MECHANISM OF ACTION

    Triptorelin is a potent inhibitor of gonadotropin secretion when given continuously. Triptorelin produces a medical castration by inhibiting the production of testosterone or estrogen through a negative feedback mechanism. After initial administration there is a transient surge in circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol. After chronic and continuous administration, usually 2 to 4 weeks after starting therapy, a sustained decrease in LH and FSH secretion and marked reduction in testicular and ovarian steroidogenesis is observed. In men, a reduction of serum testosterone concentration to a level typically seen in surgically castrated men is obtained. These effects are reversible after cessation of therapy. When administered to healthy male volunteers, single doses of triptorelin resulted in peak testosterone levels on days 2 to 4 and decreased thereafter to low levels by weeks 3 to 4. Similar profiles are observed in men with prostate cancer.

    PHARMACOKINETICS

    Triptorelin pamoate and triptorelin suspensions are administered by intramuscular depot injection; however, other non-depot formulations available outside the US may be given as subcutaneous or intramuscular injections. Triptorelin does not appear to bind to plasma proteins.[45411] [62072] After a single IV bolus of triptorelin peptide 0.5 mg to healthy male volunteers, the volume of distribution was 30 to 33 liters. Triptorelin pamoate is distributed and eliminated according to a 3-compartment model and corresponding half-lives are 6 minutes, 45 minutes, and 3 hours.[45411] The metabolism of triptorelin is unknown but is unlikely to involve hepatic cytochrome P450 enzymes. No metabolites of triptorelin have been identified. Data suggest that C-terminal fragments produced by tissue degradation are either completely degraded in the tissues, rapidly degraded in the plasma, or cleared by the kidney. Triptorelin elimination is primarily dependent on the liver but also exhibits renal clearance. Following IV administration of 0.5 mg triptorelin peptide to healthy male volunteers with normal renal function, 41.7% of the dose was excreted in the urine as intact peptide, with a total triptorelin clearance of 211.9 mL/min. The percentage of renal clearance increased to 62.3% in patients with liver disease.[45411] [62072]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none
    Triptorelin does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2D6, or CYP3A4/5 nor does it induce CYP1A2 or CYP3A4/5. Triptorelin is a poor P-gp substrate and has no inhibitory effect on P-gp.[62072]

    Intramuscular Route

    Triptorelin pamoate (Trelstar)
    After a single intramuscular injection of triptorelin pamoate to patients with prostate cancer, mean peak serum concentrations of 28.4 ng/mL, 38.5 ng/mL, and 44.1 ng/mL occurred 1 to 3 hours after the 3.75 mg, 11.25 mg, and 22.5 mg formulations, respectively. Triptorelin did not accumulate over 9 months (3.75 mg and 11.25 mg) or 12 months (22.5 mg) of treatment.
     
    Triptorelin (Triptodur)
    After an initial 22.5 mg intramuscular injection of triptorelin and a second 22.5 mg intramuscular injection 24 weeks later to children 2 to 9 years old with central precocious puberty (CPP), triptorelin peaked 4 hours post dose with a geometric mean Cmax of 39.9 and 36.5 ng/mL, respectively. Triptorelin did not accumulate after the second injection. Absorption occurred in 2 phases, a burst phase followed by a maintenance release phase. After the burst phase following the first 22.5 mg injection, geometric mean serum triptorelin levels were 0.11, 0.17, 0.05, and 0.03 ng/mL at Months 1, 2, 3, and 6, respectively, in children with CPP.