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Amevive

Generic Name: Alefacept
Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: 1-92-LFA-3 (Antigen) (human) fusion protein with immunoglobulin G1 (human hinge CH2-CH3 γ1-chain) dimer
CAS Number: 222535-22-0

Introduction

Immunosuppressive agent;1 3 recombinant dimeric fusion protein.1 2 3 4 5 6 7

Uses for Amevive

Psoriasis

Management of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.1

Slideshow: Psoriasis: Treatment Options to Manage Your Symptoms

Do not use concomitantly with other immunosuppressive agents or in patients currently receiving phototherapy; concomitant use of low-potency topical corticosteroids was permitted in clinical studies.1

Amevive Dosage and Administration

Administration

Use only under supervision of a clinician.1

Administer IV or IM; components for either IV or IM reconstitution and administration are supplied with the vials.1 (See Preparations.)

Use strict aseptic technique, since drug product contains no preservative.1

Do not filter reconstituted solution during preparation or administration.1

Do not admix with other drugs.1

IV Administration

Administer once weekly by rapid IV injection for a 12-week course.1

Before administration, remove needle used for reconstitution, attach second needle provided by manufacturer, and withdraw 0.5 mL of alefacept solution into syringe.1

Prepare 2 syringes containing 3 mL of 0.9% sodium chloride injection for use as pre- and post-administration flushes.1 Prime administration set with 3 mL 0.9% sodium chloride injection and insert into vein, then attach syringe containing alefacept to administration set and administer solution.1 After alefacept administration, flush with 3 mL 0.9% sodium chloride injection.1

Reconstitution

Reconstitute vial containing 7.5 mg of alefacept with only 0.6 mL of diluent, to provide a solution containing 7.5 mg per 0.5 mL.1 Use only the diluent supplied by manufacturer (sterile water for injection in a 10-mL single-use vial).1

With needle pointed toward side of vial, slowly inject diluent into vial.1 Swirl contents gently (dissolution generally takes <2 minutes).1 To avoid excessive foaming, do not shake vial and avoid vigorous agitation.1

Preferably, prepare immediately before use.1 Discard if not used within 4 hours.1 (See Storage under Stability.)

Rate of Administration

Administer by rapid IV injection over ≤5 seconds.1

IM Administration

Administer once weekly by IM injection for a 12-week course.1

Inject full 0.5 mL of reconstituted solution.1

Rotate injection sites; give new injections ≥2.54 cm (1 inch) from old site; do not inject in areas where skin is tender, bruised, red, or hard.1

Reconstitution

Reconstitute vial containing 15 mg of alefacept with only 0.6 mL of diluent, to provide a solution containing 15 mg per 0.5 mL.1 Use only the diluent supplied by manufacturer (sterile water for injection in a 10-mL single-use vial).1

With needle pointed toward side of vial, slowly inject diluent into vial.1 Swirl contents gently (dissolution generally takes <2 minutes).1 To avoid excessive foaming, do not shake vial and avoid vigorous agitation.1

Preferably, prepare immediately before use.1 Discard if not used within 4 hours.1 (See Storage under Stability.)

Dosage

Monitor CD4+ T-cell counts before initiation of therapy and every 2 weeks throughout the 12-week course of therapy.1 Do not initiate if CD4+ T-cell counts are below normal range.1 If CD4+ T-cell counts are <250/mm3, withhold therapy and monitor CD4+ T-cell counts weekly.1 Discontinue if CD4+ T-cell counts remain <250/mm3 for 1 month.1

Adults

Psoriasis
IV

7.5 mg once weekly for 12 weeks.1 Monitor CD4+ T-cell counts and adjust dosage accordingly.1

May initiate retreatment with additional 12-week course if CD4+ T-cell counts are within normal range and ≥12 weeks have elapsed since previous course.1

IM

15 mg once weekly for 12 weeks.1 Monitor CD4+ T-cell counts and adjust dosage accordingly.1

May initiate retreatment with additional 12-week course if CD4+ T-cell counts are within normal range and ≥12 weeks have elapsed since previous course.1

Cautions for Amevive

Contraindications

  • HIV infection.1 11 (See Lymphopenia and also see Infectious Complications under Cautions.)

  • Known hypersensitivity to alefacept or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Lymphopenia

Risk of lymphopenia, including dose-dependent reductions in circulating CD4+ and CD8+ T-cell counts.1

Do not initiate in patients with CD4+ T-cell counts below normal range.1 Monitor CD4+ T-cell counts before initiation of therapy and every 2 weeks throughout the 12-week course of therapy; dosage adjustment may be necessary.1 (See Dosage under Dosage and Administration.)

Do not use in patients with HIV infection.1 Potential for accelerated progression of HIV or increased infectious complications.1 11 (See Contraindications under Cautions.)

Malignancies

Possible increased risk of malignancies (e.g., basal or squamous cell skin cancers, melanoma, other solid tumors, lymphomas).1

Do not use in patients with history of malignancy.1 Caution advised when considering use in patients at high risk for malignancy; discontinue if malignancy develops.1

Infectious Complications

Possible increased risk of infection, including reactivation of latent infections.1

Do not use in patients with clinically important infections (e.g., HIV infection).1 (See Contraindications and also Lymphopenia, under Cautions.) Caution advised if used in patients with chronic infection or history of recurrent infections.1

Monitor carefully for manifestations of infection during and after treatment; discontinue if serious infection develops.1

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions (e.g., urticaria, angioedema) reported; if serious hypersensitivity reaction occurs, discontinue immediately and initiate appropriate therapy.1

General Precautions

Immunosuppressive Effects

Do not use concomitantly with other immunosuppressive agents or phototherapy (due to potential for excessive immunosuppression).1

Immunization

Safety and efficacy of live virus vaccine administration in patients receiving alefacept not established.1

Hepatic Effects

Asymptomatic increases in serum AST and/or ALT concentrations, fatty infiltration of the liver, hepatitis, decompensation of cirrhosis with hepatic failure, and acute hepatic failure reported during postmarketing experience; causal relationship to drug not established.1

Fully evaluate patients with manifestations of hepatic injury.1 Discontinue alefacept if clinically important hepatic injury develops.1

Antibody Formation

Possible development of low-titer antibodies to alefacept; relationship between development of antibodies and clinical response or incidence of adverse effects not observed.1 Long-term immunogenicity remains to be determined.1

Specific Populations

Pregnancy

Category B.1

Biogen Pregnancy Registry at 866-263-8483.1

Lactation

Not known whether distributed into milk; discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children.1

Geriatric Use

No overall differences in safety or efficacy relative to younger adults, but experience insufficient to exclude important differences.1 Use with caution due to increased incidence of infections and certain malignancies in geriatric patients.1

Common Adverse Effects

Pharyngitis, dizziness, increased cough, nausea, pruritus, myalgia, chills, injection site pain/inflammation, accidental injury.1

Interactions for Amevive

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Comments

Immunosuppressive agents

Possible excessive immunosuppression1

Concomitant use not recommended; optimal time between alefacept discontinuance and initiation of other agents not established1

Vaccines, live virus

Safety and efficacy not established1

Amevive Pharmacokinetics

Absorption

Bioavailability

Bioavailability after IM administration is 63%.1

Distribution

Extent

Crosses placenta in monkeys.1 Not known whether distributed into human milk.1

Elimination

Half-life

Approximately 270 hours.1

Stability

Storage

Parenteral

Powder for Injection

2–8°C.1 Protect from light; retain dose tray in carton until time of use.1

Store reconstituted solution in vial at 2–8°C; use within 4 hours.1

Actions

  • Consists of extracellular CD2-binding portion of human leukocyte function-related antigen 3 (LFA-3) linked to Fc portion (hinge region and CH2 and CH3 domains) of human IgG1.1 2 3 4 5 7

  • Interferes with T-cell activation by specifically binding to the antigen CD2 on T cells and inhibiting the interaction between LFA-3 on antigen-presenting cells and CD2.1 2 3 4 5

  • Causes reduction in subsets of CD2+ T cells (principally CD45RO+ T cells),6 presumably by bridging between CD2 on target lymphocytes and immunoglobulin Fc receptors on cytotoxic cells such as natural killer cells.1

  • Causes dose-dependent decrease in total circulating lymphocytes, principally affecting the memory effector subset of CD4+ and CD8+ T cells (i.e., CD4+CD45RO+ and CD8+CD45RO+ T cells).1 2 3 4

  • May affect activation and numbers of cells other than T cells, since CD2 also is expressed at low levels on the surface of natural killer cells and certain bone marrow B cells.1

Advice to Patients

  • Potential for reduction of lymphocyte counts, which could increase risk of infection or malignancy.1 Importance of informing clinicians promptly if any signs or symptoms of infection or malignancy occur.1

  • Necessity of administration under supervision of a clinician, with regular monitoring of T-cell counts.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed during or within 8 weeks following discontinuance.1 For any woman who becomes pregnant, availability of pregnancy registry (see Pregnancy under Cautions).1

  • Risk of serious hepatic injury.1 Importance of reporting persistent nausea, anorexia, fatigue, vomiting, abdominal pain, jaundice, easy bruising, dark urine, or pale stools to clinicians.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Alefacept (Recombinant)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

7.5 mg

Amevive (available with sterile water for injection diluent, administration set, needles, and syringe)

Biogen Idec

For injection, for IM use

15 mg

Amevive (available with sterile water for injection diluent, needles, and syringe)

Biogen Idec

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Biogen Idec, Inc. Amevive (alefacept) for injection prescribing information. Cambridge, MA; 2005 Sep.

2. 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; 47:821-33. [IDIS 490925] [PubMed 12451365]

3. Pham DQ, Bandy V, Song JC. Alefacept: a T-cell specific immunosuppressant to treat moderate to severe plaque psoriasis. Formulary. 2002; 37:346-53.

4. Ellis CN, Krueger GG, for the Alefacept Clinical Study Group. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med. 2001; 345:248-55. [IDIS 467244] [PubMed 11474662]

5. Gottlieb AB, Bos JD. Recombinantly engineered human proteins: transforming the treatment of psoriasis. Clin Immunol. 2002; 105:105-16. [PubMed 12482385]

6. Kraan MC, van Kuijk AW, Dinant HJ et al. Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis. Arthritis Rheum. 2002; 46:2776-84. [IDIS 488165] [PubMed 12384938]

7. Anon. Alefacept (Amevive) for treatment of psoriasis. Med Lett Drugs Ther. 2003; 45:31-2.

8. Lebwohl M, Christophers E, Langley R et al, for the Alefacept Clinical Study Group. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol. 2003; 139:719-27. [IDIS 499462] [PubMed 12810502]

9. Biogen, Inc, Cambridge, MA: Personal communication.

10. Center for Biologics Evaluation and Research, US Food and Drug Administration. Biologics license application approval letter for alefacept. Rockville, MD; 2003 Jan 30.

11. Bozic C. Dear healthcare provider letter: important prescribing information for Amevive (alefacept). Cambridge, MA: Biogen Idec; 2005 Oct.

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