Assisted reproductive technologies, controlled ovarian hyperstimulation, adjunctive therapy: Decapeptyl [Canadian product]: Females: Usual dose: SUBQ: 0.1 mg once daily initiated on day 2 or 3 or days 21 to 23 of menstrual cycle (or 5 to 7 days prior to expected onset of menses). Dose may be adjusted according to ovarian response as measured by ovarian ultrasound with or without serum estradiol levels. Treatment is continued until follicles achieve suitable size (typically 4 to 7 weeks).
Breast cancer, premenopausal ovarian suppression during adjuvant endocrine therapy (off-label use): IM: 3.75 mg once every 28 days ± 3 days (in combination with adjuvant endocrine therapy) for ~5 years; if receiving chemotherapy, begin ovarian suppression with the start of chemotherapy (Bellet 2016; Pagani 2014).
Breast cancer, premenopausal ovarian preservation during chemotherapy (off-label use): IM: 3.75 mg once every 28 days beginning at least 1 week prior to chemotherapy and continuing throughout chemotherapy (Lambertini 2015).
Endometrial stromal sarcoma (off-label use): IM: 3.75 mg once every 28 days for ~3 to 5 months (Jin 2015). Additional studies are necessary to further define the role of triptorelin in the management of this condition.
Endometriosis (off-label use): IM: 3.75 mg once every 4 weeks for a total of 6 doses (Bergqvist 1998; Choktanasiri 1996) or 3.75 mg once every 6 weeks for a total of 4 doses (Tse 2000) or 11.25 mg once every 3 months (Donnez 2004). Hormonal add-back therapy (such as estrogens or progestins) is recommended at the start of treatment to reduce bone mineral loss (Dunselman 2014; SOGC [Leyland 2010]). Duration of therapy is not well established (Dunselman 2014) but should be evaluated after 3 months (SOGC [Leyland 2010]); in general, use of GnRH agonists is limited to less than 6 or 12 months due to adverse events (Leone Roberti Maggiore 2014).
Paraphilia/hypersexuality, treatment (off-label use) (Guay 2009; Thibaut 1993): Males:
Note: May cause an initial increase in androgen concentrations, which may be treated with an antiandrogen (eg, flutamide, cyproterone) for 1 to 2 months (Guay 2009). Avoid use in patients with osteoporosis or active pituitary pathology.
SUBQ: Test dose: 1 mg (observe for hypersensitivity); if tolerated, follow with monthly IM injections.
IM: 3.75 mg monthly.
Prostate cancer, advanced: Trelstar:
IM: 3.75 mg once every 4 weeks or
IM: 11.25 mg once every 12 weeks or
IM: 22.5 mg once every 24 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, renal impairment increases systemic exposure to triptorelin.
There are no dosage adjustments provided in the manufacturer's labeling. However, hepatic impairment increases systemic exposure to triptorelin.
(For additional information see "Triptorelin: Pediatric drug information")
Central precocious puberty: Children ≥2 years: Triptodur: IM: 22.5 mg once every 24 weeks; discontinue therapy at appropriate age of onset of puberty.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, in adult patients, renal impairment increased systemic exposure to triptorelin.
There are no dosage adjustments provided in the manufacturer's labeling; however, in adult patients, hepatic impairment increased systemic exposure to triptorelin.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension Reconstituted, Intramuscular:
Trelstar Mixject: 11.25 mg (1 ea); 22.5 mg (1 ea) [contains polysorbate 80]
Suspension Reconstituted, Intramuscular [preservative free]:
Trelstar Mixject: 3.75 mg (1 ea); 11.25 mg (1 ea [DSC]); 22.5 mg (1 ea [DSC]) [contains polysorbate 80]
Suspension Reconstituted ER, Intramuscular:
Triptodur: 22.5 mg (1 ea) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Subcutaneous:
Decapeptyl: 0.1 mg/mL (1 mL)
Suspension Reconstituted, Intramuscular:
Trelstar: 3.75 mg (1 ea); 11.25 mg (1 ea); 22.5 mg (1 ea) [contains polysorbate 80]
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Triptodur: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208956s000lbl.pdf#page=12
IM: Administer by IM injection into the buttock (Trelstar) or into the buttock or thigh (Triptodur); alternate injection sites. Administer immediately after reconstitution. Must administer under the supervision of a health care provider.
SUBQ: Decapeptyl [Canadian product] is administered by SUBQ injection into the lower abdomen; alternate injection sites. If a dose is missed, it can be administered on the same day; however, do not double doses. Must administer under the supervision of a health care provider.
IM: Administer Triptodur by IM injection into the buttock or thigh; alternate injection sites.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Central precocious puberty: Triptodur: Treatment of central precocious puberty in patients 2 years and older
Prostate cancer (advanced): Trelstar: Palliative treatment of advanced prostate cancer
Assisted reproductive technologies: Decapeptyl [Canadian product]: Adjunctive therapy in women undergoing controlled ovarian hyperstimulation for assisted reproductive technologies (ART)
Breast cancer, premenopausal ovarian suppression during adjuvant endocrine therapy; Breast cancer, premenopausal ovarian preservation during chemotherapy; Endometrial stromal sarcoma; Endometriosis; Paraphilia/hypersexuality
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hot flash (prostate cancer: 59% to 73%; central precocious puberty: 2% to 5%), increased serum glucose (prostate cancer)
Hematologic & oncologic: Decreased hemoglobin (prostate cancer), decreased red blood cells (prostate cancer)
Hepatic: Increased serum alanine aminotransferase (prostate cancer), increased serum aspartate aminotransferase (prostate cancer), increased serum transaminases (prostate cancer)
Local: Pain at injection site (central precocious puberty: 45%; prostate cancer: 4%), erythema at injection site (central precocious puberty: 14%)
Nervous system: Headache (2% to 14%)
Neuromuscular & skeletal: Skeletal pain (prostate cancer: 12% to 13%)
Renal: Increased blood urea nitrogen (prostate cancer)
Respiratory: Nasopharyngitis (central precocious puberty: 14%)
1% to 10%:
Cardiovascular: Lower extremity edema (prostate cancer: 6%), hypertension (prostate cancer: ≤4%; central precocious puberty), chest pain (prostate cancer: 2%), peripheral edema (prostate cancer: 1%)
Dermatologic: Injection site pruritus (central precocious puberty: 2%), skin rash (prostate cancer: 2%), pruritus (prostate cancer: 1%)
Endocrine & metabolic: Decreased libido (prostate cancer: 2%), dependent edema (prostate cancer: 2%), gynecomastia (prostate cancer: 2%)
Gastrointestinal: Gastroenteritis (central precocious puberty: 7%), nausea (prostate cancer: 3%), anorexia (prostate cancer: 2%), constipation (prostate cancer: 2%), dyspepsia (prostate cancer: 2%), vomiting (prostate cancer: 2%), abdominal pain (prostate cancer: 1%), diarrhea (prostate cancer: 1%)
Genitourinary: Erectile dysfunction (prostate cancer: 10%), menstruation (central precocious puberty: 8%), testicular atrophy (prostate cancer: 8%), impotence (prostate cancer: 2% to 7%), dysuria (prostate cancer: 5%), mastalgia (prostate cancer: 2%), urinary retention (prostate cancer: 1%), urinary tract infection (prostate cancer: 1%)
Hematologic & oncologic: Anemia (prostate cancer: 1%)
Hepatic: Increased serum alkaline phosphatase (≥2%), hepatic insufficiency (prostate cancer: 1%)
Infection: Influenza (central precocious puberty: 5%)
Local: Swelling at injection site (central precocious puberty: 2%)
Nervous system: Pain (prostate cancer: 2% to 3%), dizziness (prostate cancer: 1% to 3%), anxiety (central precocious puberty: 2%), fatigue (prostate cancer: 2%), mood changes (central precocious puberty: 2%), insomnia (prostate cancer: ≤2%), emotional lability (≤1%)
Neuromuscular & skeletal: Lower extremity pain (prostate cancer: 2% to 5%), back pain (prostate cancer: ≤3%), lower limb cramps (prostate cancer: 2%), arthralgia (prostate cancer: ≤2%), asthenia (prostate cancer: 1%), myalgia (prostate cancer: 1%)
Ophthalmic: Conjunctivitis (prostate cancer: 1%), eye pain (prostate cancer: 1%)
Otic: Otitis externa (central precocious puberty: 5%)
Respiratory: Upper respiratory tract infection (central precocious puberty: 9%), cough (central precocious puberty: 7%; prostate cancer: 2%), bronchitis (central precocious puberty: 5%), pharyngitis (central precocious puberty: 5%; prostate cancer: 1%), sinusitis (central precocious puberty: 5%), dyspnea (prostate cancer: 1%)
Miscellaneous: Postoperative pain (reproductive studies: 3% to 4%), missed abortion (reproductive studies: 2%)
Frequency not defined: Endocrine & metabolic: Increased testosterone level
<1%, postmarketing, and/or case reports: Altered gonadal hormone levels (pituitary-gonadal axis suppression), anaphylactic shock, anaphylactoid shock, angioedema, cerebrovascular accident, deep vein thrombosis, hypersensitivity reaction, interstitial pulmonary disease, intracranial hypertension (Tan 2019), limb pain, myocardial infarction, pituitary apoplexy, pulmonary embolism, seizure, thrombophlebitis, transient ischemic attacks, urticaria, visual disturbance, visual impairment
Hypersensitivity to triptorelin or any component of the formulation, other gonadotropin-releasing hormone (GnRH) agonists or GnRH; pregnancy.
Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding; undiagnosed abnormal vaginal bleeding (when used for endometriosis).
Concerns related to adverse effects:
• Cardiovascular effects: Androgen-deprivation therapy (ADT) may increase the risk for cardiovascular disease (Levine 2010). Myocardial infarction, sudden cardiac death and stroke have been reported in men receiving GnRH agonists. ADT may prolong the QT/QTc interval; consider the benefits of ADT versus the risk for QT prolongation in patients with a history of QTc prolongation, congenital long QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients with medications known to prolong the QT interval.
• Decreased bone density: Use with caution in patients with risk factors for decreased bone mineral density; GnRH agonist therapy may increase risk for osteoporosis and bone fractures particularly with prolonged use.
• Hyperglycemia: Hyperglycemia and an increased risk of developing diabetes has been reported with therapy and may manifest as diabetes or worsening of glycemic control in patients with diabetes.
• Hypersensitivity reactions: Angioedema and anaphylactic shock have occurred; discontinue use if severe reaction occurs.
• Ovarian hyperstimulation syndrome: Decapeptyl [Canadian product]: Ovarian hyperstimulation syndrome (OHSS) is a rare exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable). Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; SOGC-CFAS 2011). Therapy with gonadotropins should be stopped.
• Pituitary apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with GnRH agonist administration (onset from 1 hour to usually <2 weeks); may present as sudden headache, vomiting, visual or mental status changes, and infrequently cardiovascular collapse; immediate medical attention required.
• Psychiatric effects: Symptoms of emotional lability (eg, crying, irritability, anger, aggression, impatience) have been reported with GnRH agonists, including triptorelin; monitor for the development or worsening of psychiatric symptoms.
• Seizures: Seizures have been reported with GnRH agonists, including triptorelin in patients with or without a history of seizures or other conditions or concurrent medications associated with seizures.
• Spinal cord compression: Cases of spinal cord compression, which may contribute to weakness or paralysis (possible fatal complications), have been reported; observe patients with metastatic vertebral lesions closely during the first few weeks of treatment.
• Symptom flare: Transient initial increases in gonadotropins and sex steroids leading to a worsening of symptoms may be observed during the first few weeks of therapy or after subsequent doses. Patients with prostate cancer may experience new or increased bone pain, neuropathy, hematuria, or urethral or bladder outlet obstruction. Female patients with central precocious puberty may experience transient vaginal bleeding.
Disease-related concerns:
• Urinary tract obstruction: Observe patients with urinary tract obstruction closely during the first few weeks of treatment.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
None known.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Choline C 11: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Corifollitropin Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic effect of Corifollitropin Alfa. Risk X: Avoid combination
Gallium Ga 68 PSMA-11: Androgen Deprivation Therapy Agents may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of gallium Ga 68 PSMA-11 in prostate cancer. The impact of ADT on the performance of gallium Ga 68 PSMA-11 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Indium 111 Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Piflufolastat F18: Androgen Deprivation Therapy Agents may diminish the diagnostic effect of Piflufolastat F18. Management: Androgen deprivation therapy (ADT) may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of ADT on the performance of piflufolastat F18 is unknown, but use of alternative agents should be considered. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
When used for assisted reproductive technologies (ART; not an approved use in the US), pregnancy must be ruled out prior to therapy and nonhormonal contraception should be used until menses occurs. Due to the short half-life of triptorelin (formulations used for ART), it is not expected to be present in the maternal serum at the time of embryo transfer.
Based on the mechanism of action, may impair fertility in males of reproductive potential.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to triptorelin may cause fetal harm.
Hormonal changes that occur with therapy may increase the risk of pregnancy loss. Therefore, use is contraindicated in females who are pregnant. Information following inadvertent exposure in early pregnancy is limited (Elefant 1995).
It is not known if triptorelin is present in breast milk.
Due to the potential for adverse reactions in the breastfed infant, the manufacturer recommends that a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Monitor blood glucose and/or HbA1c (periodically and as clinically necessary). Consider periodic monitoring of electrocardiograms and electrolytes in patients at risk for QT prolongation. Monitor for signs/symptoms of emerging cardiovascular disease or hypersensitivity. Monitor for development/worsening of psychiatric symptoms.
Additional monitoring (per indication):
Treatment of precocious puberty: Monitor response to therapy with LH levels after a GnRH or GnRH agonist stimulation test, basal LH, or serum sex steroid levels beginning 1 to 2 months after initiation of therapy, during therapy, and with each subsequent dose; height every 3 to 6 months; bone age (periodically).
Prostate cancer: Serum testosterone levels, prostate-specific antigen; bone density. Monitor for signs/symptoms of tumor flare.
Assisted reproductive technologies: Decapeptyl [Canadian product]: Negative pregnancy test prior to initiation of therapy; signs/symptoms of allergic reaction for 30 minutes after administration; ultrasound and/or estradiol levels to assess follicle development; ultrasound to assess number and size of follicles.
OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine specific gravity, vital signs, weight (daily or as necessary) and liver enzymes (weekly) (SOGC-CFAS 2011).
Treatment of paraphilia/hypersexuality (off-label use): The following monitoring has been recommended for other GnRH agonists: CBC (baseline, monthly for 4 months then every 6 months); serum testosterone (baseline, monthly for 4 months then every 6 months); serum LH (baseline and every 6 months), FSH (baseline), serum BUN and creatinine (baseline and every 6 months); bone density (baseline and yearly); ECG (baseline) (Reilly 2000).
Triptorelin is an agonist analog of gonadotropin releasing hormone (GnRH) and causes suppression of ovarian and testicular steroidogenesis due to decreased levels of LH and FSH with subsequent decrease in testosterone (male) and estrogen (female) levels. After chronic and continuous administration, usually 2 to 4 weeks after initiation, a sustained decrease in LH and FSH secretion occurs. When used for assisted reproductive technologies (ART), prevents premature LH surge in women undergoing controlled ovarian hyperstimulation.
Distribution: Vd: 30 to 33 L
Protein binding: None
Metabolism: Unknown; unlikely to involve CYP; no known metabolites
Half-life elimination: 2.8 ± 1.2 hours
Moderate-to-severe renal impairment: 6.6 to 7.7 hours
Hepatic impairment: 7.6 hours
Time to peak: Trelstar: 1 to 3 hours; Triptodur: 4 hours
Excretion: Urine (42% as intact peptide); hepatic
Renal function impairment: There is a decrease in total Cl proportional to decrease in CrCl and increased Vd and half-life. Patients with renal impairment had 2- to 4-fold higher exposure (AUC) values than younger healthy men.
Hepatic function impairment: The decrease in triptorelin Cl is more pronounced. Triptorelin half-life increase is similar to renal impairment. Patients with hepatic impairment had 2- to 4-fold higher exposure (AUC) values than younger healthy men.
Geriatric: Triptorelin clearance is partly correlated to total CrCl, which is well known to decrease with age.
Suspension (reconstituted) (Trelstar Mixject Intramuscular)
3.75 mg (per each): $975.89
11.25 mg (per each): $2,927.66
22.5 mg (per each): $5,855.33
Suspension Reconstituted ER (Triptodur Intramuscular)
22.5 mg (per each): $21,193.21
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