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|Histrelin Acetate

Histrelin Acetate

Trade Names:
Vantas
- Implant 50 mg

Mechanism of Action

Pharmacology

Inhibits gonadotropin secretion. Results in an initial increase in circulating levels of luteinizing hormone and follicle-stimulating hormone, leading to transient increase in concentration of gonadal steroid.

Pharmacokinetics

Absorption

C _max is 1.1 ng/mL, occurring in 12 hr. Bioavailability is 92%. Average rate of subcutaneous drug release is 56.7 mcg/day.

Distribution

Vd following subcutaneous bolus of 500 mcg is 58 L. Unbound drug in plasma is 29.5%.

Metabolism

C-terminal dealkylation and possible fragments resulting from hydrolysis. Apparent Cl after a 50 mg subcutaneous implant is approximately 174 mL/min.

Elimination

Terminal t _½ is 3.92 hr.

Indications and Usage

Palliative treatment of advanced prostate cancer.

Contraindications

Women; pediatric patients; patients hypersensitive to gonadotropin-releasing hormone (GnRH), GnRH agonist analogs, or any component of the product.

Dosage and Administration

Subcutaneous 1 implant (50 mg) for 12 mo. Implant must be removed after 12 mo, at which time another implant may be inserted to continue therapy.

General Advice

• For subcutaneous implantation only. Not for intradermal, IM, or oral administration.
• Follow manufacturers instructions regarding preparation of injection site, preparation of insertion tool, insertion of implant, and closing the incision site.

Storage/Stability

Store implant in refrigerator (36° to 46°F), in unopened glass vial with the 1.8% sterile sodium chloride solution, overwrapped in the amber plastic pouch and carton. Protect from light. Do not freeze.

Drug Interactions

None well documented.

Laboratory Test Interactions

Because of suppression of pituitary-gonadal system, results of diagnostic tests of pituitary gonadotropic and gonadal function may be affected.

Adverse Reactions

Cardiovascular

Palpitations, ventricular extrasystoles (less than 2%).

CNS

Fatigue (10%); insomnia, headache (3%); decreased libido (2%); depression, dizziness, irritability, lethargy, malaise, tremor, weakness (less than 2%).

Dermatologic

Contusion, hematoma, hypotrichosis, night sweats, pruritus, increased sweating (less than 2%).

GI

Constipation (4%); abdominal discomfort, nausea (less than 2%).

Genitourinary

Testicular atrophy, renal impairment (5%); erectile dysfunction, gynecomastia (4%); breast pain, breast tenderness, dysuria, genital pruritus (male), aggravated gynecomastia, renal calculus, aggravated hematuria, aggravated renal failure, sexual dysfunction, urinary frequency, aggravated urinary frequency, urinary retention (less than 2%).

Hematologic-Lymphatic

Anemia (less than 2%).

Hepatic

Hepatic disorder (less than 2%).

Lab Tests

Increased AST, blood glucose, blood lactate dehydrogenase, blood testosterone, and prostatic acid phosphatase, decreased creatinine clearance (less than 2%).

Local

Bruising (7%); implant site reaction (6%); pain, soreness, tenderness (4%); erythema (3%).

Metabolic-Nutritional

Weight increase (2%); increased appetite, fluid retention, food craving, hypercalcemia, hypercholesterolemia, peripheral edema, weight decrease (less than 2%).

Musculoskeletal

Arthralgia, back pain, aggravated back pain, bone pain, muscle twitching, myalgia, neck pain, pain in limb (less than 2%).

Respiratory

Exertional dyspnea (less than 2%).

Miscellaneous

Hot flashes (66%); feeling cold, flushing, pain, exacerbated pain; stent occlusion (less than 2%).

Precautions

Pregnancy

Category X .

Lactation

Undetermined.

Children

Contraindicated.

Worsening symptoms

Onset of new symptoms or worsening of symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction. Monitor patient for signs and symptoms of ureteral obstruction (eg, oliguria, lower abdominal or pelvic pain) and spinal cord compression (eg, paresthesias, numbness, tingling, loss of sphincter control, motor weakness).

Patient Information

• Advise patient that implant containing medication will be prepared and implanted by health care professionals in a health care setting.
• Explain name, action, and potential side effects of the treatment regimen. Review the treatment regimen including implantation and removal of implant, dosing schedule, duration of treatment, and monitoring that will be required.
• Advise patient to read the Patient Information leaflet before the insert is implanted and each time another histrelin implant is inserted.
• Advise patient that some pain, redness, and/or bruising at the implant insertion site may occur but that these usually go away without treatment within 2 wk. Instruct patient to contact health care provider immediately if unusual bleeding or persistent or worsening pain or redness at the insertion site occur.
• Caution patient not to wet the arm where implant was inserted for 24 hr following implantation, at which time the pressure bandage can be removed. Caution patient not to remove surgical strips but to allow the strips to fall off on their own (may take several days). Caution patient to avoid heavy lifting or strenuous exertion of the inserted arm for 7 days following implant insertion.
• Advise patient histrelin implant infrequently can be expelled from the body through the original insertion site. Advise patient to contact health care provider if the implant has been expelled.
• Advise patient pellet will deliver histrelin to the body for 12 mo, and then the implant must be removed. Inform patient that a new histrelin implant may be implanted at that time by health care provider if therapy is to be continued.
• Advise patient to contact health care provider immediately if new or worsening bone pain, weakness or loss of feeling in legs, blood in the urine, or difficulty urinating occur.
• Instruct patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.