Degarelix Acetate is a gonadotropin-releasing hormone (GnRH) antagonist used to treat adult men with advanced hormone-dependent prostate cancer.

A single initial dose of 240 mg degarelix followed by a monthly maintenance dose of 80 mg leads to a rapid decline in LH, FSH, and subsequently testosterone levels. Serum dihydrotestosterone (DHT) also decreases in parallel with testosterone.

Degarelix effectively maintains testosterone suppression well below the medical castration level of 0.5 ng/ml. Monthly maintenance dosing of 80 mg sustains this suppression in 97% of patients for at least one year. No testosterone micro-surges occur after repeat injections during treatment. After one year, the median testosterone level is 0.087 ng/ml (interquartile range 0.06–0.15; N=167).

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.

Degarelix must be reconstituted prior to administration. Degarelix is for subcutaneous use only, not to be administered intravenously. Intramuscular administration is not recommended as it has not been studied. Degarelix 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.

No formal studies on drug–drug interactions have been conducted. As androgen deprivation therapy may prolong the QTc interval, caution is required when degarelix is used together with medicines known to prolong the QTc interval or to cause torsades de pointes, such as class IA antiarrhythmics (e.g., quinidine, disopyramide), class III antiarrhythmics (e.g., amiodarone, sotalol, dofetilide, ibutilide), as well as drugs like methadone, moxifloxacin, and certain antipsychotics.

Degarelix is not metabolized by the human CYP450 enzyme system and has not shown significant induction or inhibition of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 in vitro. Therefore, clinically meaningful pharmacokinetic interactions involving these enzymes are unlikely.

Hypersensitivity to the active ingredient or to any of the excipients in this formulation.

The most frequently reported adverse effects during degarelix treatment in the confirmatory Phase III study (N=409) were mainly related to the expected physiological consequences of testosterone suppression. These included hot flushes and weight gain, occurring in 25% and 7% of patients respectively after one year of treatment, as well as injection site reactions. Transient symptoms such as chills, fever, or flu-like illness were reported within hours after dosing in 3%, 2%, and 1% of patients respectively.

Injection site reactions were primarily pain and redness (erythema), reported in 28% and 17% of patients. Less common reactions included swelling (6%), hardening (induration) (4%), and nodules (3%). These reactions were mainly associated with the starting dose. During maintenance therapy with 80 mg, the incidence per 100 injections was low: pain occurred in 3 cases, while erythema, swelling, nodules, and induration occurred in fewer than 1 case each.

Most reactions were temporary, mild to moderate in severity, and led to very few treatment discontinuations (<1%). Serious injection site complications were very rare, including infection, abscess formation, or tissue necrosis, which in some cases required surgical treatment or drainage.

Degarelix Acetate has no relevant indication for use in women. It may suppress male fertility for as long as testosterone levels remain reduced.

Elderly patients and those with mild to moderate hepatic or renal impairment do not require dose adjustment. However, patients with severe liver or kidney dysfunction have not been studied, so caution should be exercised in such cases.

Paediatric population: Degarelix Acetate is not relevant for use in children or adolescents for the treatment of adult male patients with advanced hormone-dependent prostate cancer.

There is no clinical experience regarding acute overdose of degarelix. If an overdose occurs, the patient should be carefully monitored and given appropriate supportive care if needed.

Drugs affecting (inhibiting) gonadotrophin

This medicine does not need any special storage conditions. Its chemical and physical stability after preparation has been shown for up to 2 hours at 25°C. From a microbiological standpoint, unless the reconstitution method eliminates the risk of contamination, the product should be used immediately. If not used right away, the storage time and conditions during use are the responsibility of the user.