Below are a graph and a table of the effect of Ferring’s degarelix on testosterone compared with the effect of Lupron. On December 24th Ferring announced that FDA has approved degarelix for the treatment of hormonally sensitive advanced prostate cancer.

Degarelix (generic name) is a GnRH receptor antagonist. The company says: “Degarelix achieves medical castration differently than LHRH agonists, specifically by binding reversibly to GnRH receptors on cells in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone.” How quickly? Like this :

Click here to open larger image in a new window.

Some highlights, if we can call them that, of the prescription information. Any doctor or pharmacist should share this with the patient, but package inserts are often tossed out. These excerpts do not cover everything. For the sake of readability I’ll replace TRADENAME with degarelix:

STARTING DOSE

240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL

Maintenance dose – Administration every 28 days

80 mg given as one subcutaneous injection at a concentration of 20 mg/mL
The first maintenance dose should be given 28 days after the starting dose.

How It’s Injected:

Grasp the skin of the abdomen, elevate the subcutaneous tissue. Insert the needle deeply at an angle of not less than 45 degrees.

Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the reconstituted product can no longer be used. Discontinue the procedure and discard the syringe and the needle (reconstitute a new dose for the patient).

ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 1325 patients with prostate cancer received degarelix either as a monthly treatment (60-160 mg) or as a single dose (up to 320 mg). A total of 1032 patients (78%) were treated for at least 6 months and 853 patients (64%) were treated for one year or more. The most commonly observed adverse reactions during degarelix therapy included injection site reactions (e.g. pain, erythema [redness], swelling or induration), hot flashes, increased weight, fatigue, and increases in serum levels of transaminases and gammaglutamyltransferase (GGT). The majority of the adverse reactions were Grade 1 or 2, with Grade 3/4 adverse reaction incidences of 1% or less.

Degarelix was studied in an active-controlled trial (N = 610) in which patients with prostate cancer were randomized to receive degarelix (subcutaneous) or leuprolide (intramuscular) monthly for 12 months. Adverse reactions reported in 5% of patients or more are shown in Table 1 [opens in this window].

The most frequently reported adverse reactions at the injection sites were pain (28%), erythema [redness] (17%), swelling (6%), induration [hardening] (4%) and nodule (3%). These adverse reactions were mostly transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (below 1%). Grade 3 injection site reactions occurred in 2% or less of patients receiving degarelix.

The following adverse reactions, not already listed, were reported to be drug-related by the investigator in more than or equal to 1% of patients: erectile dysfunction, gynecomastia, hyperhidrosis [sweating], testicular atrophy, and diarrhea.

Changes in bone density:

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of medical castration in men will result in decreased bone density.

Anti-degarelix antibody development has been observed in 10% of patients after treatment with degarelix for 1 year. There is no indication that the efficacy or safety of degarelix treatment is affected by antibody formation.

Effect on QT/QTc Interval

Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.

DRUG INTERACTIONS

No drug-drug interaction studies were conducted.

Degarelix is not a substrate for the human CYP450 system. Degarelix is not an inducer or inhibitor of the CYP450 system in vitro. Therefore, clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely.

Geriatric Use

Of the total number of subjects in clinical studies of  degarelix, 82% were age 65 and over, while 42% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

No pharmacokinetic studies in renally impaired patients have been conducted. At least 20-30% of a given dose of degarelix is excreted unchanged in the urine.

A population pharmacokinetic analysis of data from the randomized study demonstrated that there is no significant effect of mild renal impairment [creatinine clearance (CrCL) 50-80 mL/min] on either the degarelix concentration or testosterone concentration. Data on patients with moderate or severe renal impairment is limited and therefore degarelix should be used with caution in patients with CrCL < 50 mL/min.

Hepatic Impairment

Patients with hepatic impairment were excluded from the randomized trial.

A single dose of 1 mg degarelix administered as an intravenous infusion over 1 hour was studied in 16 nonprostate cancer patients with either mild . . .  or moderate . . .  hepatic impairment. Compared to non-prostate cancer patients with normal liver function, the exposure of degarelix decreased by 10% and 18% in patients with mild and moderate hepatic impairment, respectively. Therefore, dose adjustment is not necessary in patients with mild or moderate hepatic impairment. However, since hepatic impairment can lower degarelix exposure, it is recommended that in patients with hepatic impairment testosterone concentrations
should be monitored on a monthly basis until medical castration is achieved. Once medical castration is achieved, an every-other-month testosterone monitoring approach could be considered. Patients with severe hepatic dysfunction have not been studied and caution is therefore warranted in this group.

Before receiving  degarelix, tell your healthcare provider about all your medical conditions, including if you:
• have any heart problems
• have problems with balance of your body salts or electrolytes, such as sodium, potassium, calcium,and
magnesium
• have kidney or liver problems

Source:

Prescribing Information .pdf