Degapride

Degapride Uses, Dosage, Side Effects, Food Interaction and all others data.

Degapride is a selective gonadotrophin releasing-hormone (GnRH) antagonist that competitively and reversibly binds to the pituitary GnRH receptors, thereby rapidly reducing the release of the gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and thereby reducing the secretion of testosterone (T) by the testes. Prostatic carcinoma is known to be androgen sensitive and responds to treatment that removes the source of androgen. Unlike GnRH agonists, GnRH antagonists do not induce a LH surge with subsequent testosterone surge/tumour stimulation and potential symptomatic flare after the initiation of treatment. A single dose of 240 mg degarelix, followed by a monthly maintenance dose of 80 mg, rapidly causes a decrease in the concentrations of LH, FSH and subsequently testosterone. The serum concentration of dihydrotestosterone (DHT) decreases in a similar manner to testosterone. Degapride is effective in achieving and maintaining testosterone suppression well below medical castration level of 0.5 ng/ml. Maintenance monthly dosing of 80 mg resulted in sustained testosterone suppression in 97% of patients for at least one year. No testosterone microsurges were observed after re-injection during degarelix treatment. Median testosterone levels after one year of treatment were 0.087 ng/ml (interquartile range 0.06-0.15) N=167.

Degapride is a synthetic derivative of GnRH decapeptide, the ligand of the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. Degapride antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. LF and FSH decreases in a concentration-dependent manner. The reduction in LH leads to a decrease in testosterone release from the testes.

Trade Name Degapride
Availability Prescription only
Generic Degarelix
Degarelix Other Names Degarelix
Related Drugs estradiol, Premarin, Xtandi, Casodex, Zytiga, Lynparza
Type Injection
Formula C82H103ClN18O16
Weight Average: 1632.29
Monoisotopic: 1630.748797
Protein binding

90% of the drug is bound to plasma proteins.

Groups Approved
Therapeutic Class Drugs affecting (inhibiting) gonadotrophin
Manufacturer Ranbaxy Laboratories (sun Pharma)
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Degapride
Degapride

Uses

Degapride Acetate is a gonadotrophin releasing hormone (GnRH) antagonist used for treatment of adult male patients with advanced hormone-dependent prostate cancer.
Elderly, hepatically or renal impaired patients: There is no need to adjust the dose for the elderly or in patients with mild or moderate liver or kidney function impairment. Patients with severe liver or kidney impairment have not been studied and caution is therefore warranted.

Paediatric population: There is no relevant use of Degapride Acetate in children and adolescents in the treatment of adult male patients with advanced hormone-dependent prostate cancer.

Degapride is also used to associated treatment for these conditions: Advanced Prostate Cancer

How Degapride works

Degapride competitively inhibits GnRH receptors in the pituitary gland, preventing the release of luteinizing hormone (LH) and follicle stimulating hormone. Reduced LH suppresses testosterone release, which slows the growth and reduces the size of prostate cancers.

Dosage

Degapride dosage

Starting dose: 240 mg administered as two consecutive subcutaneous injections of 120 mg each.

Maintenance dose (monthly administration): 80 mg administered as one subcutaneous injection.

The first maintenance dose should be given one month after the starting dose.

The therapeutic effect of degarelix should be monitored by clinical parameters and prostate specific antigen (PSA) serum levels. Clinical studies have shown that testosterone (T) suppression occurs immediately after administration of the starting dose with 96% of the patients having serum testosterone levels corresponding to medical castration (T≤0.5 ng/ml) after three days and 100% after one month. Long term treatment with the maintenance dose up to 1 year shows that 97% of the patients have sustained suppressed testosterone levels (T≤0.5 ng/ml).

In case the patient's clinical response appears to be sub-optimal, it should be confirmed that serum testosterone levels are remaining sufficiently suppressed.

Since degarelix does not induce a testosterone surge it is not necessary to add an anti androgen as surge protection at initiation of therapy.

Degapride must be reconstituted prior to administration. Degapride is for subcutaneous use only, not to be administered intravenously. Intramuscular administration is not recommended as it has not been studied. Degapride is administered as a subcutaneous injection in the abdominal region. The injection site should vary periodically. Injections should be given in areas where the patient will not be exposed to pressure e.g. not close to waistband or belt and not close to the ribs.

Side Effects

The most commonly observed adverse reactions during degarelix therapy in the confirmatory phase III study (N=409) were due to the expected physiological effects of testosterone suppression, including hot flushes and weight increase (reported in 25% and 7%, respectively, of patients receiving treatment for one year), or injection site adverse reactions. Transient chills, fever or influenza like illness were reported to occur hours after dosing (in 3%, 2% and 1% of patients, respectively).

The injection site adverse reactions reported were mainly pain and erythema, reported in 28% and 17% of patients, respectively, less frequently reported were swelling (6%), induration (4%) and nodule (3%). These events occurred primarily with the starting dose whereas during maintenance therapy with the 80 mg dose, the incidence of these events pr 100 injections was: 3 for pain and <1 for erythema, swelling, nodule and induration. The reported events were mostly transient, of mild to moderate intensity and led to very few discontinuations (<1%). Serious injection site reactions were very rarely reported such as injection site infection, injection site abscess or injection site necrosis that could require surgical treatment/drainage.

Toxicity

The most commonly observed adverse reactions (> 10%) during degarelix therapy included injection site reactions (e.g., pain, erythema, swelling, or induration), hot flashes, increased weight, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Interaction

No formal drug-drug interaction studies have been performed. Since androgen deprivation treatment may prolong the QTc interval, the concomitant use of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated. Degapride is not a substrate for the human CYP450 system and has not been shown to induce or inhibit CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 to any great extent in vitro. Therefore, clinically significant pharmacokinetic drug-drug interactions in metabolism related to these isoenzymes are unlikely.

Food Interaction

No interactions found.

Volume of Distribution

Central compartment: 8.88 - 11.4 L; Peripheral compartment: 40.9 L

Elimination Route

Degapride forms a depot at the site of injection after subcutaneous administration from which the drug slowly released into circulation. After a single bolus dose of 2mg/kg, peak plasma concentrations of degarelix occured within 6 hours at a concentration of 330 ng/mL. Ki = 0.082 ng/mL and 93% of receptors were fully suppressed; MRT = 4.5 days.

Half Life

Terminal half-life: 41.5 - 70.2 days; Absorption half-life: 32.9 hours; Half-life from injection site: 1.17 days.

Clearance

Following subcutaneous administration of degarelix to prostate cancer patients the clearance is approximately 9 L/hr.

Elimination Route

Fecal (70% to 80%) and renal (20%-30% of unchanged drug)

Pregnancy & Breastfeeding use

There is no relevant indication for use of Degapride Acetate in women. Degapride Acetate may inhibit male fertility as long as the testosterone is suppressed.

Contraindication

Hypersensitivity to the active substance or to any of the excipients of Degapride Acetate.

Acute Overdose

There is no clinical experience with the effects of an acute overdose with degarelix. In the event of an overdose the patient should be monitored and appropriate supportive treatment should be given, if considered necessary.

Storage Condition

This medicinal product does not require any special storage conditions. Chemical and physical in-use stability has been demonstrated for 2 hours at 25°C. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Innovators Monograph

You find simplified version here Degapride

Degapride contains Degarelix see full prescribing information from innovator Degapride Monograph, Degapride MSDS, Degapride FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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