Administer sub-Q as an implant; insert implant in inner aspect of upper arm. Consult manufacturer’s labeling for proper methods of inserting and removing implants.
Dosage
Available as histrelinacetate; dosage expressed in terms of the salt.
Adults
Prostate Cancer
Sub-Q
One 50-mg implant every 12 months.
Remove implant 12 months after insertion. At time of implant removal, may insert another implant to continue therapy. In limited clinical studies, treatment remains effective for up to 2 years.
Prescribing Limits
Adults
Prostate Cancer
Sub-Q
Use of 2 or 4 implants provides no additional benefit beyond that produced by a single implant.
Special Populations
Renal Impairment
No dosage adjustment required. (See Special Populations under Pharmacokinetics.)
Cautions
Contraindications
Women or pediatric patients. May cause fetal harm when administered to a pregnant woman.
Known hypersensitivity to histrelin or any ingredient in the formulation, other GnRH agonists, or GnRH.
Warnings/Precautions
Warnings
Endocrine Effects
Possible transient increase in serum testosterone concentrations during first week of treatment. Worsening of signs and/or symptoms of prostate cancer and/or development of new manifestations (e.g., bone pain, neuropathy, hematuria, ureteral or bladder outlet obstruction) may occur during first few weeks of therapy.
Ureteral obstruction and spinal cord compression (which may contribute to paralysis with or without fatal complications) reported with GnRH agonists. Observe patients with metastatic vertebral lesions and/or urinary tract obstruction closely during first few weeks of therapy. If spinal cord compression or renal impairment develops, institute standard treatment.
No acute increase in serum testosterone concentration observed following removal of first implant (after 1 year of therapy) and insertion of second implant.
Renal impairment reported. Some patients had a single occurrence of mild impairment (Clcr of 30–59 mL/minute) that returned to normal by the next visit.
General Precautions
Laboratory Monitoring
To monitor response, measure serum concentrations of testosterone and PSA periodically.
Implant Complications
Implant insertion or removal is a surgical procedure. Carefully follow recommended procedures for insertion and removal of implant to minimize potential for complications or for implant expulsion.
Implants are not radio-opaque and, therefore, will not be visible on radiographs. If implant is difficult to locate by palpation, may use ultrasound and computed tomography (CT) scan.
Decrease in Bone Mineral Density
Decrease in bone mineral density possible following long-term therapy with GnRH antagonists and agonists.
Specific Populations
Pregnancy
Category X. (See Contraindications under Cautions.)
Lactation
Contraindicated in women. (See Contraindications under Cautions.)
Pediatric Use
Contraindicated in pediatric patients. (See Contraindications under Cautions.)
Geriatric Use
Studies conducted principally in patients ≥65 years of age, since prostate cancer occurs mainly in an older patient population.
Common Adverse Effects
Local or insertion site reactions (e.g., bruising, pain/soreness/tenderness, erythema), hot flushes (flashes), testicular atrophy, gynecomastia, erectile dysfunction, decreased libido, fatigue, renal impairment, constipation, headache, insomnia, weight loss.
Interactions
No formal drug interaction studies to date.
Pharmacokinetics
Absorption
Bioavailability
Following sub-Q insertion, peak serum concentrations occurred at a median of 12 hours.
Drug is delivered continuously at rate of 50–60 mcg daily over 12 months.
Special Populations
Serum histrelin concentrations are 50% higher in patients with mild to severe renal impairment (Clcr of 15–60 mL/minute). However, increased exposure not considered clinically relevant; dosage adjustment not required.
Distribution
Plasma Protein Binding
Approximately 70%.
Elimination
Elimination Route
No excretion studies to date.
Half-life
Approximately 3.92 hours following sub-Q injection of a 500-mcg dose.
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