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Pronunciation
(a LE fa sept)
Generic Available (U.S.)
No
Index Terms
Prescribing and Access 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. Contact Amevive® Start Assistance Program (ASAP) at 1-800-477-6472 to initiate treatment.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects have not been observed in animal reproduction studies. Patients who become pregnant during therapy or within 8 weeks of treatment are advised to enroll in pregnancy registry (866-834-7223).
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).
Contraindications
Hypersensitivity to alefacept or any component of the formulation; patients with HIV infection
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Hepatic injury: In postmarketing 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. Discontinue if anaphylaxis or severe reaction occurs.
• Immune suppression: May increase the risk of infection and may reactivate latent infection; monitor for new infections. Avoid use in patients with clinically important infections or a history of recurrent infections; not recommended for use in patients receiving other immunosuppressant drugs or phototherapy. Discontinue if a serious infection occurs.
• 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; withhold treatment in any patient who develops a depressed CD4+ lymphocyte count (<250 cells/μL) during treatment and monitor CD4+ lymphocyte counts weekly; permanently discontinue if CD4+ lymphocyte counts remain <250 cells/μL for 1 month.
• Malignancy: May increase the risk of malignancies; avoid use in patients with a history of systemic malignancy; use caution in patients at high risk for malignancy. Discontinue if malignancy develops during therapy.
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.
Adverse Reactions
≥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%)
Hepatic: Transaminases increased (2%; AST and ALT ≥3 times ULN)
Neuromuscular & skeletal: Myalgia (≥2%)
Respiratory: Pharyngitis (≥2%), cough (≥2%)
Miscellaneous: Antibodies to alefacept (3%; significance unknown), infection (1% requiring hospitalization), malignancies (1%)
<1%: Anaphylaxis, allergic reaction, angioedema, headache, hepatitis, hepatic failure, MI, urticaria
Metabolism/Transport Effects
None known.
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Belimumab: Alefacept may enhance the adverse/toxic effect of Belimumab. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
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
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. 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). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase risk of liver toxicity).
Storage
Store under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. Following reconstitution, may be stored for up to 4 hours at 2°C to 8°C (36°F to 46°F). Discard any unused solution within 4 hours of reconstitution.
Reconstitution
Reconstitute 15 mg vial for I.M. solution with 0.6 mL of SWFI (supplied); reconstituted solution contains 15 mg/0.5 mL of alefacept. Gently swirl to avoid excessive foaming. Do not filter reconstituted solutions.
Compatibility
Do not mix with other medications or solutions.
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: I.V.: Vd: 0.094 L/kg
Bioavailability: I.M.: 63%
Half-life elimination: I.V.: 270 hours
Excretion: Clearance: I.V.: 0.25 mL/hour/kg
Dosage
Adults:
I.M.: 15 mg once weekly; duration of treatment: 12 weeks
A second 12- week 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.
Elderly: Refer to adult dosing; use with caution since elderly patients may be at an increased risk for infections and malignancies.
Dosage adjustment in renal impairment: Use has not been evaluated in patients with renal impairment; there are no dosage adjustments provided in manufacturer's labeling.
Dosage adjustment in hepatic impairment: Use has not been evaluated in patients with hepatic impairment; there are no dosage adjustments provided in manufacturer's labeling.
Administration: I.M.
I.M. injections should be administered at least 1 inch from previous administration sites.
Monitoring Parameters
Baseline CD4+ T-lymphocyte counts prior to initiation and every 2 weeks during treatment course; weekly CD4+ T-lymphocyte counts if CD4+ counts are <250 cells/μL during therapy; severity of psoriatic lesions; signs and symptoms of infection
Dietary Considerations
Some products may contain sucrose.
Patient Education
This medication can only be administered by injection. Report immediately any pain or irritation at injection site; chills; rash; difficulty swallowing or breathing; or feelings of tightness in chest. Avoid alcohol. You will need weekly blood tests while receiving this medication. May cause nausea or muscle pain. Report unusual feelings of fatigue or weakness, signs of infection (eg, cough, runny nose, sore throat, swollen glands, mouth sores, burning on urination, fever, chills), abdominal pain, jaundice, easy bruising, dark urine, or pale stools.
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
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor closely for the development of malignancies or infections.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution:
Amevive®: 15 mg [DSC] [contains sucrose 12.5 mg; for I.M. administration]
References
Ellis CN, Mordin MM, and Adler EY, “Effects of Alefacept on Health-Related Quality of Life in Patients With Psoriasis: Results From a Randomized, Placebo-Controlled Phase II Trial,” Am J Clin Dermatol, 2003, 4(2):131-9.
Gottlieb AB and Bos JD, “Recombinantly Engineered Human Proteins: Transforming the Treatment of Psoriasis,” Clin Immunol, 2002, 105(2):105-16.
Krueger GG, Papp KA, Stough DB, et al, “A Randomized, Double-Blind, Placebo-Controlled Phase III Study Evaluating Efficacy and Tolerability of 2 Courses of Alefacept in Patients With Chronic Plaque Psoriasis,” J Am Acad Dermatol, 2002, 47(6):821-33.
Menter A, Gottlieb A, Feldman SR,, et al, "Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis: Section 1. Overview of Psoriasis and Guidelines of Care for the Treatment of Psoriasis With Biologics," J Am Acad Dermatol, 2008, 58(5):826-50.
Weinberg JM and Tutrone WD, “Biologic Therapy for Psoriasis: The T-Cell-Targeted Therapies Efalizumab and Alefacept,” Cutis, 2003, 71(1):41-5.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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