Histrelin

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
Brands: Vantas

Special Alerts:

[Posted 10/20/2010] ISSUE: Gonadotropin-Releasing Hormone (GnRH) agonists will have new safety information added to the Warnings and Precautions section of the drug labels. This new information warns about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer.

BACKGROUND: GnRH agonists are approved to treat the symptoms (palliative treatment) of advanced prostate cancer. The benefits of GnRH agonist use for earlier stages of prostate cancer that have not spread (non-metastatic prostate cancer) have not been established. FDA’s notification to manufacturers of GnRH agonists to add this safety information is based on the Agency’s review of several published studies. Most of the studies reviewed by FDA reported small but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists.

RECOMMENDATIONS: Healthcare professionals should evaluate patients for risk factors for these diseases and carefully weigh the benefits and risks of using GnRH agonists before determining appropriate treatment for prostate cancer. Patients who are receiving treatment with GnRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c). Healthcare professionals should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice. For more information visit the FDA website at: and .

[Posted 05/03/2010] FDA notified healthcare professionals and patients of FDA’s preliminary and ongoing review which suggests an increase in the risk of diabetes and certain cardiovascular diseases in men treated with GnRH agonists, drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer.

Most of the studies reviewed by FDA reported small, but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists. FDA’s review is ongoing and the agency has not made any conclusions about GnRH agonists and whether they increase the risk of diabetes and cardiovascular disease in patients receiving these medications for prostate cancer.

Healthcare professionals and patients should be aware of these potential safety issues and carefully weigh the benefits and risks of GnRH agonists when determining treatment choices. FDA recommends that patients receiving GnRH agonists should be monitored for development of diabetes and cardiovascular disease. Patients should not stop their treatment with GnRH agonists unless told to do so by their healthcare professional.

Some GnRH agonists are also used in women and in children for other indications than those above. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women and children taking GnRH agonists. For more information visit the FDA website at: and .

Introduction

Antineoplastic agent; a synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone [LHRH], gonadorelin).¹

Uses for Histrelin

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Prostate Cancer

Palliative treatment of advanced prostate cancer.¹

Histrelin Dosage and Administration

Administration

Sub-Q Administration

Administer sub-Q as an implant; insert implant in inner aspect of upper arm.¹ Consult manufacturer’s labeling for proper methods of inserting and removing implants.¹

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as histrelin acetate; dosage expressed in terms of the salt.¹

Adults

Prostate Cancer

Sub-Q

One 50-mg implant every 12 months.¹

Remove implant 12 months after insertion.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}

Prescribing Limits

Adults

Prostate Cancer

Sub-Q

Use of 2 or 4 implants provides no additional benefit beyond that produced by a single implant.^{1 2}

Special Populations

Renal Impairment

No dosage adjustment required.¹ (See Special Populations under Pharmacokinetics.)

Cautions for Histrelin

Contraindications

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  Women or pediatric patients.¹ May cause fetal harm when administered to a pregnant woman.¹

  
  


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  Known hypersensitivity to histrelin or any ingredient in the formulation, other GnRH agonists, or GnRH.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Endocrine Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible transient increase in serum testosterone concentrations during first week of treatment.¹ 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.¹

Ureteral obstruction and spinal cord compression (which may contribute to paralysis with or without fatal complications) reported with GnRH agonists.¹ Observe patients with metastatic vertebral lesions and/or urinary tract obstruction closely during first few weeks of therapy.¹ If spinal cord compression or renal impairment develops, institute standard treatment.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

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic reactions reported with synthetic GnRH or GnRH agonists.¹

Major Toxicities

Renal Effects

Renal impairment reported.¹ Some patients had a single occurrence of mild impairment (Cl_cr of 30–59 mL/minute) that returned to normal by the next visit.¹

General Precautions

Laboratory Monitoring

To monitor response, measure serum concentrations of testosterone and PSA periodically.¹

Implant Complications

Implant insertion or removal is a surgical procedure.¹ Carefully follow recommended procedures for insertion and removal of implant to minimize potential for complications or for implant expulsion.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 and computed tomography (CT) scan.¹

Decrease in Bone Mineral Density

Decrease in bone mineral density possible following long-term therapy with GnRH antagonists and agonists.^{1 3}

Specific Populations

Pregnancy

Category X.¹ (See Contraindications under Cautions.)

Lactation

Contraindicated in women.¹ (See Contraindications under Cautions.)

Pediatric Use

Contraindicated in pediatric patients.¹ (See Contraindications under Cautions.)

Geriatric Use

Studies conducted principally in patients ≥65 years of age,¹ since prostate cancer occurs mainly in an older patient population.³

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

Histrelin Pharmacokinetics

Absorption

Bioavailability

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

Special Populations

Serum histrelin concentrations are 50% higher in patients with mild to severe renal impairment (Cl_cr of 15–60 mL/minute).¹ However, increased exposure not considered clinically relevant; dosage adjustment not required.¹

Distribution

Plasma Protein Binding

Approximately 70%.³

Elimination

Elimination Route

No excretion studies to date.¹

Half-life

Approximately 3.92 hours following sub-Q injection of a 500-mcg dose.³

Stability

Storage

Sub-Q

Implant

2–8°C in unopened glass vial, overwrapped in amber plastic pouch and carton.¹ Do not freeze.¹ Protect from light.¹

ActionsActions

• 
  

  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 Following long-term and continuous administration (generally, 2–4 weeks after initiation of therapy), secretion of LH and FSH is decreased, 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

  
  


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  Not active when given orally.¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of reading and understanding the manufacturer’s patient information leaflet.^{1 3}

  
  


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  Importance of protecting the arm in which the implant was inserted from moisture for 24 hours and refraining from heavy lifting or strenuous exertion with that arm for 7 days after implant insertion.¹

  
  


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  Importance of understanding required monitoring procedures.¹

  
  


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  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  
  


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  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Histrelin Acetate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Implants	50 mg	Vantas	Valera

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions December 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Valera Pharmaceutical Inc. Vantas (histrelin implant) prescribing information. Cranbury, NJ; 2004 Oct.

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.

More Histrelin resources

• Histrelin Side Effects (in more detail)
• Histrelin Use in Pregnancy & Breastfeeding
• Histrelin Drug Interactions
• Histrelin Support Group
• 3 Reviews for Histrelin - Add your own review/rating

• Histrelin Implant MedFacts Consumer Leaflet (Wolters Kluwer)


• histrelin Subcutaneous Advanced Consumer (Micromedex) - Includes Dosage Information


• Supprelin LA Prescribing Information (FDA)


• Supprelin LA Implant MedFacts Consumer Leaflet (Wolters Kluwer)


• Vantas Prescribing Information (FDA)


• Vantas Consumer Overview

Compare Histrelin with other medications

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• Prostate Cancer