Histrelin
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.
Pharmacodynamic
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.
In the treatment of Central Precocious Puberty, this is relevant as 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
- Release Rate: 50-60 mcg/day (Vantas); 65 mcg/day (Supprelin LA)
- Bioavailability: 92%
- Duration: 1 year
- Metabolism
- Peptide fragments resulting from hydrolysis are also likely metabolites.
Dosage
Adult
Palliative Treatment of Advanced Prostate Cancer
Vantas: 1 implant SC q12Months (50 mg/implant [delivers ~50 mcg/day])
Pediatric
Central Precocious Puberty
Supprelin LA: 1 implant SC q12Months (50 mg/implant [delivers 65 mcg/day])
Side effects
anemia , kidney stone , Insomnia , Headache , constipation , flushing , palpitations , Peripheral edema , Weight increase , decreased libido , tiredness , GynecomastiaInteractions
Disopyramide , Ziprasidone , Amiodarone , Papaverine , Pimozide , Thioridazine , Sotalol , Citalopram , Lumefantrine / artemether , Arsenic trioxide , Efavirenz , Bepridil , Clozapine , escitalopram , Quinidine , saquinavir , Droperidol , Anagrelide , Cisapride , Fingolimod , Methadone , Moxifloxacin , Nilotinib , Haloperidol , Dolasetron , vandetanib , sparfloxacin , Procainamide , Dofetilide , Inotuzumab , Halofantrine , Grepafloxacin , Paliperidone , Entrectinib , bedaquiline , Gemtuzumab , vemurafenibAlerts
Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists
Cases of spinal cord compression, which may contribute to weakness or paralysis with or without fatal complications, have been reported with GnRH agonists
Convulsions reported in patients receiving GnRH agonists; reports with GnRH agonists have included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs; convulsions also reported in patients in the absence of any of the conditions listed
Psychiatric events reported in patients taking GnRH agonists; postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression; monitor for development or worsening of psychiatric symptoms during treatment
Reports of MI, sudden cardiac death, and stroke in men treated with GnRH agonists
QT prolongation
- Electrolyte abnormalities should be corrected
- Consider periodic monitoring of ECG and electrolytes
Points of recommendation
Histrelin is given in a tiny implant inserted under the skin on the inside of your upper arm. You will receive this implant with a minor surgical procedure in a clinic or doctor's office.
It is best to place the implant into your non-dominant arm (your left arm if you are right-handed). Be sure to tell your doctor which arm you use most often.
The incision in your skin may be closed with stitches or surgical strips. Follow your doctor's instructions about caring for the incision and keeping it bandaged and clean until it heals completely. Keep your arm dry for at least 24 hours.
You will most likely be able to feel the implant through your skin, but it should not cause pain or discomfort.
A histrelin implant is usually left in place for 12 months and then must be removed through a surgical incision. Do not try to remove the implant yourself. Your doctor will determine whether you need another implant for continued treatment.
Call your doctor if you have any pain, swelling, tenderness, itching, tingling, bruising, or redness where the implant was inserted, or if the implant comes through the skin or falls out.
You may have a temporary increase in precocious puberty symptoms for a week or so after you have received the Supprelin LA implant.
To be sure this medicine is helping your condition, you may need frequent blood tests. Your blood work will help your doctor determine how long to treat you with histrelin.
Histrelin can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using histrelin.
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