Alefacept

Pronunciation: a-LEF-a-sept
Class: Antipsoriatic, Immunosuppressive

Trade Names

Amevive
- Injection, lyophilized powder for solution 15 mg

Pharmacology

Interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, cluster of differentiation 2 (CD2), and inhibiting the interaction between CD2 and its ligand, leukocyte function–associated antigen 3 (LFA-3).

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Pharmacokinetics

Absorption

Bioavailability is 63% (IM).

Distribution

The mean Vd is 94 mL/kg (IV).

Elimination

The mean elimination half-life and Cl are approximately 270 h and 0.25 mL/kg, respectively, following IV injection.

Indications and Usage

For the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

Contraindications

HIV infection.

Dosage and Administration

Adults

IM 15 mg once weekly for 12 weeks. Therapy should not be initiated if CD4+ T lymphocytes are below normal. After a minimum of a 12-wk interval since the initial treatment, re-treatment with an additional 12-wk course may be initiated, provided the CD4+ T-lymphocyte counts are within normal range. If CD4+ T lymphocytes fall below 250 cells/mcL at any time during therapy, withhold dosing and institute weekly monitoring. Discontinue therapy if the counts remain below 250 cells/mcL for 1 mo.

General Advice

  • Reconstitute powder with supplied sterile water for injection.
  • Do not shake or vigorously agitate vial during reconstitution.
  • Do not filter solution during preparation or administration.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • Rotate IM injection sites. Give new injections at least 1 inch from old site and never into areas where the skin is bruised, tender, erythematous, or indurated.
  • Do not add other medications to solutions containing alefacept.
  • Each vial is for single patient use only.

Storage/Stability

Store vial refrigerated at 36° to 46°F. Do not freeze. Store in original carton until time of use to protect from light. Use reconstituted product immediately or within 4 h if stored in the refrigerator. Discard if not used within 4 h of reconstitution.

Drug Interactions

Cyclosporine

Cyclosporine concentrations may be altered. Monitor cyclosporine whole-blood concentrations when starting or stopping alefacept. Adjust the cyclosporine dose as needed.

Immunosuppressive agents

Patients receiving other immunosuppressive agents should not receive concurrent therapy with alefacept because of the possibility of excessive immunosuppression.

Theophylline

Theophylline concentrations may be altered. Monitor theophylline serum concentrations when starting or stopping alefacept. Adjust the theophylline dose as needed.

Vaccines

The safety and efficacy of vaccines, specifically live or live-attenuated vaccines, administered to patients being treated with alefacept have not been studied. Vaccine effectiveness may be reduced. If coadministration cannot be avoided, the patient should be evaluated for immunological competence.

Warfarin

The anticoagulant effect of warfarin may be altered. Monitor anticoagulant activity when starting or stopping alefacept. Adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

Coronary artery disorder, MI.

CNS

Dizziness.

Dermatologic

Pruritus.

GI

Nausea.

Hematologic

Decreased CD8+ T lymphocytes (59%); decreased CD4+ T lymphocytes (48%); decreased total lymphocytes (22%).

Hepatic

ALT and/or AST elevation (2%); asymptomatic transaminase elevation, fatty infiltration of the liver, hepatitis, severe liver failure (postmarketing).

Local

Injection-site reaction (16%); pain (7%); bleeding, inflammation (4%); edema, nonspecific reaction (2%); mass (1%).

Respiratory

Increased cough, pharyngitis.

Miscellaneous

Chills (6%); malignancy, serious infections (1%); cellulitis, Clostridium difficile colitis, hypersensitivity reactions (eg, anaphylactic reactions, angioedema, urticaria), myalgia, opportunistic infection, sepsis, UTI (postmarketing).

Precautions

Monitor

Ensure CD4+ T-lymphocyte counts are determined prior to starting therapy and every 2 wk throughout entire 12-wk course of therapy. If CD4+ T-lymphocyte counts are below 250 cells/mcL, alefacept dosing should be withheld and weekly monitoring instituted. Monitor patients for signs and symptoms of infection during or after a course of alefacept. New infections should be closely monitored.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution because the incidence of infection and certain malignancies is higher.

Hypersensitivity

May occur.

Hepatic effects

Liver injury, including asymptomatic transaminase elevation, fatty infiltration of the liver, hepatitis, decompensation of cirrhosis with liver failure, and acute liver failure, may occur. Discontinue therapy in patients who develop significant clinical signs of liver injury.

HIV patients

Because alefacept reduces CD4+ lymphocyte counts, disease progression may be accelerated and complications may be increased. Do not administer to patients infected with HIV.

Lymphopenia

Alefacept induces dose-dependent reductions in circulating CD4+ and CD8+ lymphocyte counts. Do not initiate therapy in patients with a CD4+ T-lymphocyte count below normal. Withhold therapy if CD4+ T-lymphocyte count is below 250 cells/mcL. Discontinue therapy if CD4+ T-lymphocyte counts are below 250 cells/mcL for 1 mo.

Malignancies

May increase the risk of malignancies.

Phototherapy

Avoid alefacept in patients receiving phototherapy because excessive immunosuppression may occur.

Serious infections

May increase the risk of infection and reactivate latent, chronic infections.

Overdosage

Symptoms

Arthralgia, chills, headache, sinusitis.

Patient Information

  • Advise patients that this medication will be prepared and administered by a health care provider in a medical setting.
  • Advise patients to report any of the following symptoms to health care provider: abdominal pain, anorexia, dark urine or pale stools, easy bruising, intolerable injection-site reactions, fatigue, fever or other signs of infection, jaundice, persistent nausea, sore throat, vomiting.
  • Advise women to notify their health care provider if they are pregnant or planning to become pregnant during and for 8 wk following discontinuation of therapy.
  • Instruct women to notify their health care provider if they are considering breast-feeding while taking this medication.
  • Instruct patients to promptly notify their health care provider if urticaria or signs or angioedema (eg, facial edema) develop.
  • Inform patients that the reduction in lymphocyte counts could increase their chances of developing an infection or a malignancy. Advise patients to inform their health care provider promptly if they develop any signs of an infection or malignancy while undergoing a course of treatment with alefacept.

Copyright © 2009 Wolters Kluwer Health.

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