Class: Antineoplastic Agents
Chemical Name: 6-[1-phenylmethyl)-d-histidine]-9-(N-ethyl-l-prolinamide)-10-deglycinamide-luteinizing hormone-releasing factor (pig)
Molecular Formula: C66H86N18O12
CAS Number: 76712-82-8
Antineoplastic agent; a synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone [LHRH], gonadorelin).1
Uses for Histrelin
Palliative treatment of advanced prostate cancer.1
Histrelin Dosage and Administration
Available as histrelin acetate; dosage expressed in terms of the salt.1
One 50-mg implant every 12 months; delivers 50 mcg of histrelin acetate daily.1
Remove implant 12 months after insertion; the implant has been designed to allow for a few additional weeks of histrelin release to allow for flexibility in scheduling removal.1 At time of implant removal, may insert another implant to continue therapy.1 In limited clinical studies, treatment remains effective for up to 2 years.1 3
No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)
Cautions for Histrelin
Known hypersensitivity to histrelin or any ingredient in the formulation, other GnRH agonists, or GnRH.1
Women who are or may become pregnant.1
Fetal/Neonatal Morbidity and Mortality
Expected hormonal changes increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman; teratogenic and fetotoxic in nonclinical studies.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1
Initial Worsening of Hormone-dependent Disease
Possible 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) due to transient increase in serum testosterone concentrations during first few weeks of therapy.1
Ureteral obstruction (may cause renal impairment) and spinal cord compression (may result in paralysis) reported with GnRH agonists.1 Observe patients with metastatic vertebral lesions and/or urinary tract obstruction closely during first few weeks of therapy.1
No acute increase in serum testosterone concentration observed following removal of first implant (after 1 year of therapy) and insertion of second implant.1
Possible hyperglycemia and increased risk of diabetes in patients receiving GnRH agonists for treatment of prostate cancer.1 5 Studies evaluating risk of diabetes in women and children receiving GnRH agonists not performed to date.4
Evaluate patients for risk factors for diabetes and carefully weigh benefits and risks of GnRH agonist therapy before selecting treatment for prostate cancer.5
Possible increased risk of cardiovascular disease (e.g., MI, sudden cardiac death, stroke) in patients receiving GnRH agonists for treatment of prostate cancer.1 5 Studies evaluating risk of cardiovascular disease in women and children receiving GnRH agonists not performed to date.4
Anaphylactic reactions reported with synthetic GnRH or GnRH agonists.1
Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.1 Most cases occur within 2 weeks of the first dose, sometimes within the first hour.1 If manifestations occur (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse), immediate medical attention required.1 In most cases, pituitary adenoma diagnosed.1
To monitor response, measure serum concentrations of testosterone and PSA periodically.1
Implants are not radio-opaque and, therefore, will not be visible on radiographs.1 If implant is difficult to locate by palpation, may use ultrasound, magnetic resonance imaging (MRI), and/or computed tomography (CT) scan.1
Decrease in Bone Mineral Density
Category X.1 (See Contraindications under Cautions and also see Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)
Not indicated for use in pediatric patients.1 (See Contraindications under Cautions.)
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.1
Interactions for Histrelin
No formal drug interaction studies to date.1
Following sub-Q insertion, peak serum concentrations occurred at a median of 12 hours.1
Drug is delivered continuously at rate of 50–60 mcg daily over 12 months.1
Serum histrelin concentrations are 50% higher in patients with mild to severe renal impairment (Clcr of 15–60 mL/minute).1 However, increased exposure not considered clinically relevant; dosage adjustment not required.1
Plasma Protein Binding
No excretion studies to date.1
Approximately 3.92 hours following sub-Q injection of a 500-mcg dose.3
2–8°C in unopened glass vial, overwrapped in amber plastic pouch and carton.1 May be exposed to 25°C for 7 days.1 Do not freeze.1 Protect from light.1 Store implantation kit only at room temperature.1
Antineoplastic agent; a synthetic nonapeptide analog of GnRH (LHRH, gonadorelin).1
Causes a transient surge in circulating concentrations of LH, FSH, and gonadal steroids (testosterone and dihydrotestosterone in males) following initial administration.1 However, long-term and continuous administration (generally, 2–4 weeks after initiation of therapy) results in decreased levels of LH and FSH due to reversible down-regulation of GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes, resulting in marked reduction in serum testosterone concentrations.1
Reductions in serum testosterone concentrations following histrelin therapy comparable to those achieved after surgical castration (i.e., <50 ng/dL).1
Commercially available as nonbiodegradable, diffusion-controlled implant.1
Not active when given orally.1
Advice to Patients
Importance of protecting the affected arm following implant insertion; keep arm clean and dry (avoid bathing and swimming) for 24 hours, keep bandage in place and do not bump arm for several days, and refrain from heavy lifting or strenuous exertion with the arm for 7 days.1 6
Importance of notifying clinician of unusual bleeding, redness, or pain at insertion site.6
Importance of informing patients that serum testosterone concentrations may increase transiently following initiation of therapy.1 Risk of worsening symptoms of prostate cancer during initial weeks of therapy.1 Importance of notifying clinician immediately in case of new or worsening bone pain, weakness or loss of sensation in legs, blood in urine, or difficulty urinating or inability to urinate.6
Risk of decreased bone mineral density and osteoporosis.6
Possibility of increased risk of MI, sudden cardiac death, and stroke in men receiving GnRH agonists for treatment of prostate cancer.1 5 Importance of being monitored for manifestations of cardiovascular disease.1 5
Importance of promptly reporting sudden onset of headache, vomiting, or visual changes to clinicians.1
Importance of notifying clinician of known or suspected implant expulsion (can occur through original incision site).6 This occurs infrequently.6 Importance of informing patients that tests (e.g., ultrasound, CT scan) may be required to locate implant prior to removal.6
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
1. Endo Pharmaceuticals Solutions Inc. Vantas (histrelin implant) prescribing information. Chadds Ford, PA; 2011 Mar. Available at . Accessed 2011 May 26.
2. Schlegel PN, Kuzma P, Frick J et al. Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin. Urology. 2001; 58:578-82. [PubMed 11597543]
3. Valera Pharmaceuticals Inc., Cranbury, NJ: Personal communication.
4. Food and Drug Administration. GnRH agonists: safety review of drug class used to treat prostate cancer (sold under the brand names Lupron, Zoladex, Trelstar, Viadur, Vantas, Eligard, Synarel, and generics). Rockville, MD; 2010 May 3. From FDA web site (http: / / www.fda.gov / Safety / MedWatch / SafetyInformation / SafetyAlertsforHumanMedicalProducts / ucm210576.htm).
5. Food and Drug Administration. GnRH agonists: label change--increased risk of diabetes and cardiovascular disease (update). Rockville, MD; 2010 Oct 20. From FDA web site (http: / / www.fda.gov / Safety / MedWatch / SafetyInformation / SafetyAlertsforHumanMedicalProducts / ucm230359.htm).
6. Endo Pharmaceuticals Solutions Inc. Vantas (histrelin acetate) implant patient labeling. Chadds Ford, PA; 2011 Mar. Available at . Accessed 2011 May 26.