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Vantas (histrelin acetate) subcutaneous implant

Summary about Vantas

Vantas (histrelin acetate) implant is a sterile, non-biodegradable, diffusion-controlled hydrogel polymer reservoir containing histrelin acetate, a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH).

Vantas is designed to deliver approximately 50 mcg histrelin acetate per day (equivalent to approximately 41 mcg histrelin per day) over 12 months. The sterile VANTAS implant looks like a small thin flexible tube and consists of a 50-mg histrelin acetate drug core inside a 3.5 cm by 3 mm, cylindrical hydrogel polymer reservoir. The implant may appear partially to completely full with variation in color from off-white to light brown. The color may be uneven within the core.

 

A single use, sterile Insertion Tool is provided along with the implant that may be used for the placement of the implant into the subcutaneous tissue of the inner aspect of the upper arm. The Insertion Tool is enclosed in a sterile bag and is provided separately from the implant in the Implantation Kit.

Vantas can cause side effects such as crying spells, anger, aggression, and feeling restless or irritable. Call your doctor if you have any new or worsening mental problems.

Before you receive a Vantas implant, tell your doctor if you have painful or difficult urination, diabetes, heart disease, coronary artery disease, liver disease, a history of heart attack or stroke, osteoporosis, or a condition affecting your spine.

Call your doctor at once if you have a serious side effect such as severe numbness or tingling in your legs or feet, muscle weakness, problems with balance or coordination, loss of bladder or bowel control, urinating more or less than usual, sudden numbness or severe headache, problems with speech or vision, increased thirst or urination, excessive hunger, or chest pain spreading to the arm or shoulder.

A Vantas implant is usually left in place for 12 months and then removed. Your doctor will determine at that time whether you need to receive another implant for treatment of your symptoms.

 

 

Vantas (histrelin acetate)

Active Ingredient

Histrelin acetate

Administration Route

Subcutaneous

Alcohol Warning

No data about interaction

Available Strength

Subcutaneous implant: 50 mg histrelin acetate

Breastfeeding Warning

Not indicated for use in adult women.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

The effects in the nursing infant are unknown.

Clinical Pharmacology

Pharmacodynamics

Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Consequently, secondary sexual development ceases to progress in most patients. Additionally, linear growth velocity is slowed which improves the chance of attaining predicted adult height

Pharmacokinetics

Absorption

Following subcutaneous insertion of one VANTAS implant in advanced prostate cancer patients (n = 17), peak serum concentrations of 1.10 ± 0.375 ng/mL (mean ± SD) occurred at a median of 12 hours. Continuous subcutaneous release was evident, as serum levels were sustained throughout the 52 week dosing period (see Figure 1). The mean serum histrelin concentration at the end of the 52 week treatment duration was 0.13 ± 0.065 ng/mL. When histrelin serum concentrations were measured following a second implant inserted after 52 weeks, the observed serum concentrations over 8 weeks following the second implant were comparable to the same period following the first implant. The average rate of subcutaneous drug release from 41 implants assayed for residual drug content was 56.7 ± 7.71 mcg/day, over the 52 week dosing period. The relative bioavailability for the VANTAS implant in prostate cancer patients with normal renal and hepatic function compared to a subcutaneous bolus dose in healthy male volunteers was 92%. Serum histrelin concentrations were proportional to dose after one, two or four 50 mg VANTAS implants (50, 100 or 200 mg as histrelin acetate) in 42 prostate cancer patients.

Distribution

The apparent volume of distribution of histrelin following a subcutaneous bolus dose (500 mcg) in healthy volunteers was 58.4 ± 7.86 L. The fraction of drug unbound in plasma measured in vitrowas 29.5% ± 8.9% (mean ± SD).

Metabolism

An in vitro drug metabolism study using human hepatocytes identified a single histrelin metabolite resulting from C-terminal dealkylation. Peptide fragments resulting from hydrolysis are also likely metabolites. Following a subcutaneous bolus dose in healthy volunteers the apparent clearance of histrelin was 179 ± 37.8 mL/min (mean ± SD) and the terminal half-life was 3.92 ± 1.01 hr (mean ± SD). The apparent clearance following a 50 mg (as histrelin acetate) VANTAS implant in 17 prostate cancer patients was 174 ± 56.5 mL/min (mean ± SD).

Excretion

No drug excretion study was conducted with VANTAS implants.

Special Populations:

Geriatrics: The majority (89.9%) of the 138 patients studied in the pivotal clinical trial were age 65 and over.

Pediatrics: VANTAS is not indicated for use in pediatric patients.

Race: When serum histrelin concentrations were compared for 7 Hispanic, 30 Black and 77 Caucasian patients, average serum histrelin concentrations were similar.

Renal Insufficiency: When average serum histrelin concentrations were compared between 42 prostate cancer patients with mild to severe renal impairment (CLcr: 15-60 mL/min) and 92 patients with no renal or hepatic impairment, levels were approximately 50% higher in those patients with renal impairment (0.392 ng/mL versus 0.264 ng/mL). These changes in exposure as a result of renal impairment are not considered to be clinically relevant. Therefore, no changes in drug dosing are warranted for these patient subpopulations.

Hepatic insufficiency: The influence of hepatic insufficiency on histrelin pharmacokinetics has not been adequately studied.

Cost

Approximate Retail Price according https://www.drugs.com/price-guide/vantas

Subcutaneous implant:

  • 50 mg (1 implant): $4,422.86      

Dosage Form

Subcutaneous implant

Dose Schedule

The recommended dose of VANTAS is one implant for 12 months. Each implant contains 50 mg histrelin acetate to deliver 41 mg histrelin. The implant is inserted subcutaneously in the inner aspect of the upper arm and provides continuous release of histrelin (50 mcg/day) for 12 months of hormonal therapy. VANTAS should be removed after 12 months of therapy (the implant has been designed to allow for a few additional weeks of histrelin release, in order to allow flexibility of medical appointments). At the time an implant is removed, another implant may be inserted to continue therapy.

Drug Class

L02AE – Gonadotropin releasing hormone analogues

Drug Unit

mg

Food Warning

No formal drug-drug, drug-food, or drug-herb interaction studies were performed with Vantas.

Included In
Health Insurance Plan

No data

Interacting Drugs

Overview: No formal drug-drug, drug-food, or drug-herb interaction studies were performed with Vantas.

Drug-Laboratory Interactions: Therapy with Vantas  results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after Vantas therapy may be affected. Vantas decreased mean serum insulin-like growth factor-1 (IGF-1) levels by approximately 11% in one study. Vantas increased the serum concentration of dehydroepiandrosterone (DHEA) in 8 of 36 patients in another study.

Is Available Generically

No. There is currently no therapeutically equivalent version of Vantas available.

Is Proprietary

Yes

Label Details

https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021732s015lbl.pdf

Legal Status

Legal.

Is not subject to the Controlled Substances Act.

Manufacturer

Endo Pharmaceuticals Solutions Inc.

Maximum Intake

One implant per year

Mechanism of Action

Histrelin is a gonadotropin releasing hormone (GnRH) agonist that acts as a potent inhibitor of gonadotropin when administered as an implant that delivers continuous therapeutic doses. Following an initial stimulatory phase with increased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males), continuous administration of histrelin acetate results in decreased levels of LH and FSH due to a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes.

Non Proprietary Name

Histrelin acetate

Overdosage

There have been no reports of overdose in Vantas clinical trials. High doses of histrelin acetate injection in animal studies were generally associated only with effects attributed to the expected pharmacology. The method of drug delivery makes accidental or intentional overdosage unlikely.

Pregnancy Category


US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Pregnancy Warning

This drug can cause fetal harm when administered to a pregnant woman. Spontaneous abortions may occur. Major fetal abnormalities, increased fetal mortality, decreased fetal weights, and reduced fertility have been observed in animal studies. In nonclinical studies, histrelin was teratogenic and fetotoxic.

Prescribing Info

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022058s006lbl.pdf

Prescription Status

Prescription drug

Proprietary Name

Vantas

Related Drugs

Bicalutamide, Leuprolide, Triptorelin, Goserelin, Buserelin

RxCUI

606382

Warning


Transient Increase in Serum TestosteroneVANTAS causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction.Spinal Cord Compression and Urinary Tract ObstructionCases of spinal cord compression, which may result in paralysis, and ureteral obstruction, which may cause renal impairment, have been reported with GnRH agonists. Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy.Difficulty Locating or Removing ImplantIn all clinical trials combined, an implant was not recovered in 8 patients. For two of these serum testosterone rose above castrate level and the implant was neither palpable nor visualized with ultrasound. These two implants were believed to have been extruded without appreciation by the patients. In the other six, serum testosterone remained below the castrate level, but the implant was not palpable. No further diagnostic tests were conducted. One of these patients underwent in-clinic surgical exploration that did not locate the implant.Implant insertion is a surgical procedure. Careful adherence to the recommended procedure for implant insertion and removal is advised to minimize the potential for complications and for implant expulsion. In addition, patients should be instructed to refrain from wetting the arm for 24 hours and from heavy lifting or strenuous exertion of the inserted arm for 7 days after implant insertion.Hyperglycemia and Diabetes

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Cardiovascular Disease

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Laboratory Tests

Response to VANTAS should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically, especially if the anticipated clinical or biochemical response to treatment has not been achieved.

Results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions

 

Links:

http://www.endo.com/File%20Library/Products/Prescribing%20Information/Vantas_prescribing_information.html
https://www.drugs.com/mtm/histrelin-implant.html
https://www.drugbank.ca/drugs/DB06788

 

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