Abarelix

Pronunciation

(a ba REL iks)

U.S. Brand Names

Plenaxis™

Synonyms

PPI-149; R-3827

Generic Available

Use

Palliative treatment of advanced symptomatic prostate cancer; treatment is limited to men who are not candidates for LHRH therapy, refuse surgical castration, and have one or more of the following complications due to metastases or local encroachment: 1) risk of neurological compromise, 2) ureteral or bladder outlet obstruction, or 3) severe bone pain (persisting despite narcotic analgesia)

Restrictions

Abarelix is not distributed through retail pharmacies. Prescribing and distribution of abarelix is limited to physicians and hospital pharmacies participating in the Plenaxis™ PLUS program. See Additional Information, or contact Praecis Pharmaceuticals at www.plenaxisplus.com or by calling 1-877-772-3247.

Pregnancy Risk Factor

Pregnancy Implications

Not indicated for use in women; may cause fetal harm if administered to a pregnant woman.

Lactation

Excretion in breast milk unknown/not indicated in women

Contraindications

Hypersensitivity to abarelix or any component of the formulation

Warnings/Precautions

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Has been associated with immediate-onset allergic reactions; may occur with initial dose and risk increases with duration of treatment. Observe for signs/symptoms of allergic reactions (which may include hypotension and/or syncope) for at least 30 minutes following each injection. Abarelix may cause prolongation of the QT interval; consider risk:benefit in patients with baseline QTc values >450 msec or patients receiving concurrent medications which prolong the QTc interval (class Ia and class III antiarrhythmics). Efficacy may diminish during prolonged treatment, particularly in patients weighing >225 pounds; monitor serum testosterone levels to identify treatment failures. Monitor transaminase levels and hepatic function during therapy. Extended treatment may result in a decrease in bone mineral density. Not indicated for use in women or children.

Adverse Reactions

>10%:

Cardiovascular: Hot flushes (79%), peripheral edema (15%)

Central nervous system: Sleep disturbance (44%), pain (31%), dizziness (12%), headache (12%)

Endocrine & metabolic: Breast enlargement (30%), nipple discharge/tenderness (20%)

Gastrointestinal: Constipation (15%), diarrhea (11%)

Neuromuscular & skeletal: Back pain (17%)

Respiratory: Upper respiratory infection (12%)

1% to 10%:

Central nervous system: Fatigue (10%)

Endocrine & metabolic: Serum triglycerides increased (10%)

Gastrointestinal: Nausea (10%)

Genitourinary: Dysuria (10%), micturition frequency (10%), urinary retention (10%), urinary tract infection (10%)

Hepatic: Transaminases increased (2% to 8%)

Miscellaneous: Allergic reactions (urticaria, pruritus, syncope, hypotension): risk increases with prolonged treatment (in clinical trials, cumulative risk increased from 0.5% at 56 days to 2.9% at 676 days of therapy)

Overdosage/Toxicology

No experience in overdose. Treatment is symptomatic and supportive.

Drug Interactions

No formal drug interaction studies have been conducted.

QTc-prolonging agents: Additive effects on QTc prolongation may occur with concurrent therapy. Life-threatening ventricular arrhythmias may result. Example drugs include class Ia and class III antiarrhythmics, cisapride, selected quinolones, erythromycin, pimozide, mesoridazine, and thioridazine.

Stability

Store at room temperature: 25°C (77°F), excursions permitted to 15°C to 30°C (58°F to 86°F). Reconstitute vial with 2.2 mL of NS; reconstituted solutions contain abarelix 50 mg/mL. Reconstituted solution is stable for at least 8 hours at 30°C. Because it contains no preservative, manufacturer recommends administration within 1 hour of reconstitution.

Mechanism of Action

Competes with naturally occurring GnRH for binding on receptors of the pituitary. Suppresses LH and FSH, resulting in decreased testosterone. Unlike LHRH agonists, does not induce an initial rise in serum testosterone.

Pharmacodynamics/Kinetics

Distribution: Vd: 4040 L (± 1607)

Metabolism: Hepatic, via peptide hydrolysis

Half-life elimination: 13 days

Time to peak, serum: 3 days (following I.M. administration)

Excretion: Urine (13% unchanged drug)

Dosage

I.M.: Male prostate cancer: 100 mg administered on days 1, 15, 29 (week 4), then every 4 weeks

Administration

Administer intramuscularly (to the buttock).

Monitoring Parameters

Signs/symptoms of allergic reaction (for at least 30 minutes after each injection). Obtain transaminase levels at baseline and periodically during treatment. Serum testosterone (to identify treatment failure) just prior to abarelix administration, beginning on day 29 and every 8 weeks thereafter. PSA and bone mineral density may be monitored as needed.

Reference Range

Efficacy may be monitored by suppression of serum testosterone <50 ng/dL

Patient Education

Inform prescriber of any prescription, OTC medication, or herbal products you are using. and any allergies you have. Do not take any new medications during therapy without consulting prescriber. This drug must be administered via injections. You will be monitored closely following the injections. Report immediately any feelings of flushing, dizziness, difficulty swallowing or breathing, or chest tightness. You will be scheduled for injections and frequent laboratory tests. It is important to maintain adequate nutrition (frequent small meals) and hydration (2 L/day) unless advised to restrict fluids by prescriber). You may experience hot flashes (cool clothes and temperatures may help); swelling of extremities; sleep disturbances, dizziness, headache (use caution when driving or engaging in hazardous tasks until response to drug is known); breast enlargement, nipple tenderness/discharge; gastrointestinal disturbances (frequent small meals and frequent mouth care may help); constipation (increased dietary fiber and fluid and increased exercise may help; diarrhea (boiled milk or yogurt may help); back pain (consult prescriber for analgesic). Report any palpitations or chest pain, respiratory difficulty, rash, or any other persistent adverse reaction.

Additional Information

Prior to distribution, Praecis Pharmaceuticals must enroll prescribing physicians and/or hospital pharmacies in the Plenaxis™ user safety program (Plenaxis™ PLUS). A Physician Attestation form must be used to document the physician's qualifications and acceptance of responsibilities concerning patient education and adverse effect reporting. Physicians must obtain the patient's signature and personally co-sign the two-part Plenaxis™ Patient Information leaflet. The original signed copy should be retained in the patient's medical record while the other copy should be given to the patient. Hospital pharmacies must submit a hospital pharmacy agreement form to allow dispensing, which will be limited to physicians enrolled in the prescriber's registry. Confirmation of physician enrollment may be obtained by calling 1-866-753-6294. All doses must be dispensed with a Patient Information leaflet. Distributors must restrict shipment to physicians or hospital pharmacies enrolled in the Plenaxis™ prescribing program. Additional details and/or forms may be obtained through Praecis Pharmaceuticals at www.plenaxisplus.com or by calling 1-877-772-3247.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Sleep disturbances are common; may cause sedation

Mental Health: Effects on Psychiatric Treatment

May cause QTc prolongation; use caution with ziprasidone, pimozide, thioridazine, and mesoridazine

Oncology: Emetic Potential

Low (10%)

Oncology: Vesicant

Dosage Forms

Injection, powder for reconstitution [preservative free]: 113 mg [provides 100 mg/2 mL depot suspension when reconstituted; packaged with diluent and syringe]

References

"Abarelix: Abarelix-depot-F, Abarelix-depot-M, Abarelix-L, PPI 149, R 3827," Drugs R D , 2003, 4(3):161-6.

McLeod D, Zinner N, Tomera K, et al, "A Phase 3, Multicenter, Open-Label, Randomized Study of Abarelix Versus Leuprolide Acetate in Men With Prostate Cancer," Urology , 2001, 58(5):756-61.

Trachtenberg J, Gittleman M, Steidle C, et al, "A Phase 3, Multicenter, Open Label, Randomized Study of Abarelix Versus Leuprolide Plus Daily Antiandrogen in Men With Prostate Cancer," J Urol , 2002, 167(4):1670-4.

Wong SL, Lau DR, Baughman SA, et al, "Pharmacokinetics and Pharmacodynamics of Abarelix, a Gonadotropin-Releasing Hormone Antagonist, After Subcutaneous Continuous Infusion in Patients With Prostate Cancer," Clin Pharmacol Ther , 2003, 73(4):304-11.

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