Alefacept

U.S. BRAND NAMES — Amevive®

PHARMACOLOGIC CATEGORY
Monoclonal Antibody

DOSING: ADULTS — Psoriasis (moderate-to-severe chronic plaque psoriasis):

I.M.: 15 mg once weekly; usual duration of treatment: 12 weeks

Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.

Note: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and every 2 weeks during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cells/µL for longer than 1 month.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — No dosage adjustment required.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution:
Amevive®: 15 mg [for I.M. administration; contains sucrose 12.5 mg; supplied with SWFI]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [I.M. administration]:
Amevive®: 15 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — I.M. injections should be administered at least 1 inch from previous administration sites.

COMPATIBILITY — Do not mix with other medications or solutions.

USE — Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy

ADVERSE REACTIONS SIGNIFICANT
≥ 10%:
Hematologic: Lymphopenia (up to 10% of patients required temporary discontinuation, up to 17% during a second course of therapy)
Local: Injection site reactions (up to 16% of patients; includes pain, inflammation, bleeding, edema, or other reaction)

1% to 10%:
Central nervous system: Chills (6%; primarily during intravenous administration), dizziness (≥ 2%)
Dermatologic: Pruritus (≥ 2%)
Gastrointestinal: Nausea (≥ 2%)
Neuromuscular & skeletal: Myalgia (≥ 2%)
Respiratory: Pharyngitis (≥ 2%), cough increased (≥ 2%)
Miscellaneous: Malignancies (1% vs 0.5% in placebo), antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization)

<1% (Limited to important or life-threatening): Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, transaminases increased (≥ 3 times ULN), urticaria

CONTRAINDICATIONS — Hypersensitivity to alefacept or any component of the formulation; history of severe malignancy; patients with HIV infection or other clinically-important infections

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Hepatic injury: In post-marketing reports, significant transaminase elevations, as well as rare cases of hepatitis, fatty liver, decompensation of cirrhosis, and acute hepatic failure have occurred (causal relationship not established). Discontinue if signs and symptoms of hepatic injury occur. Hypersensitivity reactions: Has been associated with hypersensitivity reactions; rare anaphylaxis also reported. Discontinue use if severe reaction occurs. Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients receiving other immunosuppressant drugs or phototherapy. Infusion reactions: Acute infusion reactions may occur. Medication and equipment for management should be available for immediate use. Lymphopenia: Induces a decline in circulating T-lymphocytes (CD4+ and CD8+); CD4+ lymphocyte counts should be monitored every 2 weeks throughout therapy. Do not initiate in pre-existing depression of CD4+ lymphocytes and withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/µL) during treatment; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/µL for 1 month. Malignancy: May increase the risk of malignancies; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.

Special populations: Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.

RESTRICTIONS — Alefacept will be distributed directly to physician offices or to a specialty pharmacy; injections are intended to be administered in the physician's office

DRUG INTERACTIONS
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase risk of liver toxicity).

PREGNANCY RISK FACTOR — B (show table)

PREGNANCY IMPLICATIONS — Effects in pregnancy are not known. Teratogenic effects have not been observed in animal studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-263-8483).

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — It is not known whether alefacept is excreted in breast milk. Since alefacept is an immunosuppressant, and transfer of proteins into breast milk may occur, breast-feeding women are cautioned to discontinue breast-feeding or to discontinue use of the drug while breast-feeding (recommendations per manufacturer).

MONITORING PARAMETERS — Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; severity of psoriatic lesions; signs and symptoms of infection

CANADIAN BRAND NAMES — Amevive®

INTERNATIONAL BRAND NAMES — Amevive (AR, CH, IL, NO)

MECHANISM OF ACTION — Binds to CD2, a receptor on the surface of lymphocytes, inhibiting their interaction with leukocyte functional antigen 3 (LFA-3). Interaction between CD2 and LFA-3 is important for the activation of T lymphocytes in psoriasis. Activated T lymphocytes secrete a number of inflammatory mediators, including interferon gamma, which are involved in psoriasis. Since CD2 is primarily expressed on T lymphocytes, treatment results in a reduction in CD4+ and CD8+ T lymphocytes, with lesser effects on other cell populations (NK and B lymphocytes).

PHARMACODYNAMICS / KINETICS
Distribution: Vd: 0.094 L/kg

Bioavailability: 63% (following I.M. administration)

Half-life: 270 hours (following I.V. administration)

Excretion: Clearance: 0.25 mL/hour/kg

PATIENT INFORMATION — Report headache or unusual fatigue; increased nausea or abdominal pain; cough, runny nose, difficulty breathing; chest pain or persistent dizziness; fatigue, muscle pain or weakness, back pain; fever or chills; mouth sores; vaginal itching or discharge; sore throat; unhealed sores; or frequent infections. May cause liver damage; report persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, dark urine, pale stools, easy bruising. It is important to keep appointments for blood cell monitoring. Notify prescriber if pregnancy occurs during therapy or within 8 weeks of treatment.