Triptodur (triptorelin) extended-release injectable suspension

Triptodur (triptorelin)

Active Ingredient

Administration Route

Alcohol Warning

Available Strength

Breastfeeding Warning

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

There is a potential for serious adverse reactions in nursing infants.

Clinical Pharmacology

Following the first administration, there is a transient surge in circulating levels of LH, FSH, testosterone, and estradiol. After chronic and continuous administration, by 4 weeks after initiation of therapy, a sustained decrease in LH and FSH secretion and marked reduction in sex steroids are observed.

Pharmacokinetics

Absorption

After an initial intramuscular TRIPTODUR 22.5 mg injection and a second 22.5 mg intramuscular injection 24 weeks later in children 2 to 9 years old with CPP, triptorelin peaked 4 hours postdose with a geometric mean Cmax of 39.9 and 36.5 ng/mL, respectively. No apparent accumulation of triptorelin occurred after the second injection. Absorption occurred in two phases, a burst phase followed by a maintenance release phase. In children with CPP, following the burst phase after 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.

Distribution

There is no evidence that triptorelin, at clinically relevant concentrations, binds to plasma proteins.

Elimination

Metabolism

The metabolism of triptorelin in humans is unknown, but is unlikely to involve hepatic microsomal enzymes (cytochrome P450). Thus far no metabolites of triptorelin have been identified. Pharmacokinetic data suggest that C-terminal fragments produced by tissue degradation are either completely degraded in the tissues, or rapidly degraded in plasma, or cleared by the kidneys.

Excretion

Triptorelin is eliminated by both the liver and the kidneys. Following intravenous administration of 0.5 mg triptorelin peptide to six healthy male volunteers with a creatinine clearance of 149.9 mL/min, 41.7% of the dose was excreted in urine as intact peptide with a total triptorelin clearance of 211.9 mL/min. This percentage increased to 62.3% in patients with liver disease who have a lower creatinine clearance (89.9 mL/min). It has also been observed that the nonrenal clearance of triptorelin (patient anuric, Clcreat = 0) was 76.2 mL/min, thus indicating that the nonrenal elimination of triptorelin is mainly dependent on the liver.

Specific Populations

Renal Impairment

After intravenous bolus injection of 0.5 mg triptorelin in adults, the two distribution half-lives were unaffected by renal impairment. However, renal insufficiency led to a decrease in total triptorelin clearance proportional to the decrease in creatinine clearance as well as increases in volume of distribution and consequently, an increase in the elimination half-life. Adult male subjects with moderate or severe renal impairment had approximately 2-fold higher exposure (AUC values) than young healthy adult males.

Hepatic Impairment

After intravenous bolus injection of 0.5 mg triptorelin in adults, the two distribution half-lives were unaffected by hepatic impairment. In adult males with hepatic insufficiency, triptorelin clearance was reduced and exposure (AUC) was increased 3.7-fold compared to young healthy adult males.

Cost

Intramuscular Powder For Injection, Extended Release:

• 22.5 mg (1 powder for injection): $17,130.10

Dosage Form

Dose Schedule

The dosage of TRIPTODUR is 22.5 mg reconstituted with accompanying diluent (sterile water) 2 mL, and administered as a single intramuscular injection once every 24 weeks.

TRIPTODUR treatment should be discontinued at the appropriate age of onset of puberty at the discretion of the physician.

Monitoring

Monitor response to TRIPTODUR with LH levels after a GnRH or GnRH agonist stimulation test, basal LH, or serum concentration of sex steroid levels beginning 1 to 2 months following initiation of therapy, during therapy as necessary to confirm maintenance of efficacy, and with each subsequent dose.

Measure height (for calculation of growth rate) every 3-6 months and monitor bone age periodically.

Noncompliance with drug regimen or inadequate dosing may result in inadequate control of the pubertal process with gonadotropins and/or sex steroids increasing above prepubertal levels. If the dose of TRIPTODUR is not adequate switching to an alternative GnRH agonist for the treatment of CPP with the ability for dose adjustment may be necessary.

Drug Class

Drug Unit

Food Warning

Included In
Health Insurance Plan

Interacting Drugs

Results of in vitro studies show that drug-drug interactions with triptorelin are unlikely. However, in the absence of relevant data and as a precaution, hyperprolactinemic drugs should not be used concomitantly with triptorelin since hyperprolactinemia reduces the number of pituitary GnRH receptors.

Drug-Laboratory Test Interactions

Administration of TRIPTODUR results in suppression of the pituitary-gonadal system.

The effect of TRIPTODUR on pituitary and gonadal function is expected to disappear within six to twelve months after treatment discontinuation. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment or after discontinuation of treatment may be affected.

Is Available Generically

Is Proprietary

Label Details

Legal Status

Is not subject to the Controlled Substances Act.

Manufacturer

Maximum Intake

Mechanism of Action

Non Proprietary Name

Overdosage

Pregnancy Category

Pregnancy Warning

Animal studies during organogenesis showed embryo-fetal toxicities of pre-implantation loss, increased resorption, and reduced number of viable fetuses. There are no adequate or well-controlled studies in pregnant women. Expected treatment related hormonal changes increase the risk for pregnancy loss.

Prescribing Info

Prescription Status

Proprietary Name

Related Drugs

RxCUI

Warning