TRIPTODUR (triptorelin)

TRIPTODUR (triptorelin) for extended-release injectable suspension

TRIPTODUR (triptorelin) for extended-release injectable suspension

TRIPTODUR contains the pamoate salt of triptorelin, a synthetic decapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LHRH). The chemical name of triptorelin pamoate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycine amide (pamoate salt). The molecular weight is 1699.9.

TRIPTODUR for extended release injectable suspension for intramuscular use is provided as a sterile, lyophilized, biodegradable microgranule formulation in a single-dose vial, co-packaged with a syringe containing 2 mL Sterile Water for Injection for reconstitution of the lyophilisate. The triptorelin formulation is comprised of 22.5 mg triptorelin (equivalent to 31 mg triptorelin pamoate), poly-d,l-lactide-co-glycolide (183 mg), mannitol (74 mg), carboxymethylcellulose sodium (26 mg), and polysorbate 80 (1.7 mg). When 2 mL Sterile Water for Injection is added to the vial containing TRIPTODUR and mixed, a suspension is formed which is intended as a single intramuscular injection.

Mechanism of Action

Triptorelin is a GnRH agonist.

Pharmacodynamics

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.

INDICATIONS AND USAGE

TRIPTODUR is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP).

DOSAGE AND ADMINISTRATION

TRIPTODUR must be administered under the supervision of a physician.

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.

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Reconstitution and Administration Instructions

Please read these instructions completely before you begin.

  • Use appropriate aseptic technique for preparation and administration.
  • Screw the plunger rod into the barrel end of the prefilled sterile water diluent syringe.
TRIPTODUR (triptorelin)
  • Remove the cap from the syringe barrel.
  • Firmly attach one of the 21-gauge sterile safety needles onto the prefilled sterile water diluent syringe with a push and clockwise twist.  This 21-gauge needle will only be used for reconstitution of the product
TRIPTODUR (triptorelin)
  • Pull back on the safety cover towards the syringe and away from the 21-gauge needle.  Then pull the clear needle shield off.
  • Insert the 21-gauge needle to inject the Sterile Water diluent into the vial. Do not release the plunger rod. Gently swirl the vial ensuring the diluent rinses the sides of the vial. The reconstituted solution is a milky suspension.
triptodur
TRIPTODUR (triptorelin)

Important: Once mixed, proceed to the next steps and administer withoutvdelay.

  • Invert the vial and move back the syringe in order to position the end of the 21-gauge needle very near the level of the stopper, making sure the needle lumen is still completely in the vial.
  • Pull back the plunger rod slowly to withdraw the reconstituted product into the syringe, withdrawing as much of the reconstituted product into the syringe as possible.
TRIPTODUR (triptorelin)
  • Push the safety cover forward toward the needle until you hear and/or feel it lock. Then remove the first 21-gauge needle by grasping the needle hub to disconnect the needle from the syringe and discard it. This (first) 21-gauge needle will no longer be used.
TRIPTODUR (triptorelin)
  • Firmly attach the second sterile needle onto the syringe pull back the safety cover towards the syringe. This 21-gauge needle will be used for administration.
TRIPTODUR (triptorelin)
  • Firmly attach the second sterile needle onto the syringe pull back the safety cover towards the syringe. This 21-gauge needle will be used for administration.
  • Prime the 21-gauge needle to first remove air from the syringe, inspect the suspension visually for particulate matter and discoloration. If the suspension appears milky and homogenous without visible aggregates or precipitates then administer the suspension immediately.
TRIPTODUR (triptorelin)
  • Inject the patient preferably in either buttock or thigh using the entire contents of the syringe.
TRIPTODUR (triptorelin)
  • The injection of the suspension should be performed relatively rapidly and in a steady and uninterrupted manner in order to avoid any potential blockage of the needle.

After administering the injection, immediately activate the safety cover:

  • Center your thumb or forefinger on the textured finger pad area of the safety cover and push it forward over the needle until you hear or feel it lock.
  • Use the one-handed technique and activate the mechanism away from yourself and others.
  • Immediately discard the syringe assembly into a suitable sharps container.

CONTRAINDICATIONS

Hypersensitivity: TRIPTODUR is contraindicated in individuals with a known hypersensitivity to triptorelin, any other component of the product, or other GnRH agonists or GnRH

Pregnancy: TRIPTODUR may cause fetal harm

WARNINGS AND PRECAUTIONS

Initial Rise of Gonadotropins and Sex Steroid Levels: During the early phase of initial therapy or after subsequent doses, 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.

Psychiatric Events: Psychiatric events have been reported in patients taking GnRH agonists, including triptorelin. Postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with TRIPTODUR

Convulsions: Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including triptorelin. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above

Pseudotumor CerebriIdiopathic Intracranial Hypertension: Pseudotumor cerebri (idiopathic intracranial hypertension) has been reported in pediatric patients receiving GnRH agonists, including triptorelin. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

Adverse drug reactions

The following adverse reactions have been identified during postapproval use of triptorelin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity Reactions: Anaphylactic shock, anaphylactoid reaction, angioedema, urticaria.
Cardiovascular: Hypertension.
Psychiatric: Emotional lability, such as crying, irritability, impatience, anger, and aggression. Depression, including rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.
Nervous System: Convulsions, pseudotumor cerebri (idiopathic intracranial hypertension)
Vision Disorders: Visual impairment, visual disturbance

DRUG INTERACTIONS

Drug-Drug Interactions: 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.

USE IN SPECIFIC POPULATIONS

Pregnancy: TRIPTODUR is contraindicated in women who are pregnant since expected hormonal changes that occur with TRIPTODUR treatment increase the risk for pregnancy loss. Available data with triptorelin use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, TRIPTODUR may cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus.

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Lactation: There are no data on the presence of triptorelin in human milk, or the effects of the drug on the breastfed infant, or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TRIPTODUR and any potential adverse effects on the breastfed child from TRIPTODUR or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness of TRIPTODUR have been established in pediatric patients 2 years of age and older based on a single-arm open-label study of 44 children 2-9 years of age with CPP. The safety and effectiveness of TRIPTODUR have not been established in pediatric patients less than 2 years old.

Renal Impairment: TRIPTODUR has not been studied in children with renal impairment. Adult subjects with renal impairment had higher exposure than young healthy adult males.

Hepatic Impairment: TRIPTODUR has not been studied in children with hepatic impairment. Adult subjects with hepatic impairment had higher exposure than young healthy adult males

OVERDOSAGE

There is no experience with overdosage in clinical trials of triptorelin. If overdosage occurs, therapy should be discontinued and appropriate supportive and symptomatic treatment administered.

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