Raptiva

Generic Name: Efalizumab
Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: Immunoglobulin G1, anti-(human CD11a (antigen) (human-mouse monoclonal hu1124 γ1-chain), disulfide with human-mouse monoclonal hu1124 light chain, dimer
CAS Number: 214745-43-4

Warning(s)

Special Alerts:

[UPDATE 04/08/2009] Genentech and FDA notified healthcare professionals of the voluntary, phased withdrawal of efalizumab (Raptiva), a medication for treatment of psoriasis, from the U.S. market due to a potential risk to patients of developing progressive multifocal leukoencephalopathy (PML). By June 8, 2009, efalizumab will no longer be available in the United States. Prescribers are being asked not to initiate efalizumab treatment for any new patients. Prescribers should immediately begin discussing with patients currently using efalizumab how to transition to alternative therapies. The FDA strongly recommends that patients work with their health care professional to transition to alternative therapies for psoriasis.

[Posted 02/19/2009] FDA issued a Public Health Advisory to notify healthcare professionals of three confirmed, and one possible report of progressive multifocal leukoencephalopathy (PML), a rare brain infection, in patients using the psoriasis drug efalizumab (Raptiva). In October 2008, the labeling for efalizumab was changed to highlight, in a Boxed Warning, the risks of life-threatening infections, including PML. In addition, FDA directed Genentech, the manufacturer of efalizumab, to develop a Risk Evaluation and Mitigation Strategy, or REMS, to ensure that patients receive risk information about efalizumab. The FDA is reviewing this latest information. The agency will take appropriate steps to ensure that the risks of efalizumab do not outweigh its benefits, that patients prescribed efalizumab are clearly informed of the signs and symptoms of PML, and that health care professionals carefully monitor patients for the possible development of PML. The Public Health Advisory provides recommendations for healthcare providers and patients when treatment with this product is considered.

For more information visit the FDA website at: , , , and .

Warning(s)

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Infectious Complications
  • Serious infections (sometimes leading to hospitalization or death), including bacterial sepsis, viral meningitis, invasive fungal disease, and other opportunistic infections, reported.1 (See Infectious Complications under Cautions.)

  • Inform patients of symptoms of infection; closely monitor patients for manifestations of infection during and after treatment with efalizumab.1

  • If serious infection develops, discontinue efalizumab and institute appropriate therapy.1

  • Progressive Multifocal Leukoencephalopathy (PML)
  • PML secondary to JC virus infection reported.1 (See Nervous System Effects under Cautions.)

Introduction

Immunosuppressive agent; a recombinant humanized anti-CD11a monoclonal antibody.1 2 3 5 6 7

Uses for Raptiva

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Psoriasis

Management of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.1 2 5

Slideshow: Psoriasis - Treatment Options to Manage Your Symptoms

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

Raptiva Dosage and Administration

Administration

Use only under the supervision of a clinician.1

May be self-administered if the clinician determines that the patient and/or caregiver is competent to safely administer the drug after appropriate training and with medical follow-up as necessary.1

Administer by sub-Q injection.1

Sub-Q Administration.

Administer using the sterile, disposable syringe and needles supplied by the manufacturer.1

Prior to administration, replace the needle used for reconstitution with the second needle supplied by the manufacturer; withdraw the dose to be given into the syringe, keeping the needle below the level of liquid.1

Administer into the thighs, upper arms, buttocks, or abdomen; rotate injection sites.1

Reconstitution

Reconstitute by slowly injecting 1.3 mL of sterile water for injection from the prefilled diluent syringe supplied by the manufacturer into the vial containing efalizumab.1 Do not reconstitute with other diluents.1

Swirl the contents gently using a rotary motion (dissolution generally takes <5 minutes).1 To avoid foaming, do not shake the vial.1

Do not admix with other drugs.1

Preferably, prepare immediately before use.1 Discard if not used within 8 hours.1 (See Storage under Stability.) Discard unused portions of reconstituted solution.1

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adults

Psoriasis
Sub-Q

Initial dose of 0.7 mg/kg, followed by 1 mg/kg (maximum 200 mg) once weekly.1 (See First-dose Reactions under Cautions.)

Prescribing Limits

Adults

Psoriasis
Sub-Q

Maximum single dose: 200 mg.1

Safety and efficacy of efalizumab therapy beyond one year’s duration not established.1

Cautions for Raptiva

Contraindications

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

Warnings/Precautions

Warnings

Infectious Complications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible increased risk of infections, including reactivation of latent chronic infections.1 11

Serious bacterial, viral, fungal, and opportunistic infections (sometimes leading to hospitalization or death), including pneumonia, sepsis, meningitis, and encephalitis, reported.1 JC virus infection causing PML also reported.1 (See Nervous System Effects under Cautions.) Other serious infections reported include cytomegaloviral infections; necrotizing fasciitis; blastomyces, cryptococcal, and tuberculous pneumonia; serious herpes infection; bacterial sepsis with seeding of distant sites; severe pneumonia with severe neutropenia; and worsening of infection (e.g., cellulitis, pneumonia) despite anti-infective therapy.1 11

Do not use in patients with clinically important infections; caution advised if used in patients with chronic infection or a history of recurrent infections.1

Closely monitor patients for manifestations of infection during and after treatment with efalizumab; if serious infection develops, discontinue efalizumab and institute appropriate therapy.1

Malignancies

Risk of malignancies may be increased in patients receiving immunosuppressive agents.1 Some patients receiving efalizumab in clinical trials developed malignancies; the role of efalizumab in the development of malignancies is not known.1

Caution advised when considering use in patients at high risk for malignancy or in those with a history of malignancy; discontinue if malignancy develops.1

Immune-mediated Thrombocytopenia

Risk of thrombocytopenia.1 11

Monitor platelet counts frequently (e.g., monthly) during initiation of therapy and less frequently (e.g., every 3 months) during continued therapy.1

Monitor closely for manifestations of thrombocytopenia.1

Discontinue if thrombocytopenia develops.1

Immune-mediated Hemolytic Anemia

Risk of hemolytic anemia.1 11

Discontinue if hemolytic anemia develops.1

Worsening of Psoriasis

Worsening of psoriasis, sometimes requiring hospitalization or alternate antipsoriatic therapy, can occur during or following discontinuance of efalizumab therapy.1

Closely observe patients, including those not responding to efalizumab therapy, following discontinuance of the drug; institute appropriate treatment for psoriasis as necessary.1

Dosage tapering strategies (e.g., gradual weekly tapering, alternate-week administration) do not appear to prevent recurrence but may lengthen the time to relapse.9 Some clinicians suggest that the rate of psoriasis rebound may be reduced by initiating alternative antipsoriatic therapy upon disease recurrence or by transitioning to alternative antipsoriatic therapy following efalizumab discontinuance, particularly in patients demonstrating partial or no response to efalizumab.8

Nervous System Effects

PML secondary to JC virus infection reported.1 Consider possibility of PML in any patient presenting with new-onset neurologic manifestations.1 (See Advice to Patients.) Consider diagnostic evaluation, including consultation with a neurologist, brain magnetic resonance imaging (MRI), and lumbar puncture, as clinically indicated.1 If PML develops, discontinue efalizumab.1

Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, facial palsy, and transverse myelitis reported.1 Exercise caution when considering efalizumab therapy in patients with preexisting or new-onset adverse nervous system effects.1

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., dyspnea, asthma, urticaria, angioedema, maculopapular rash) have been reported.1

General Precautions

Arthritic Episodes

Arthritic episodes have been reported, including new-onset or recurrent severe arthritis and psoriatic arthritis.1 Arthritis improved with or without antiarthritic therapy in patients who discontinued efalizumab.1

Immunosuppressive Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Safety and efficacy in combination with other immunosuppressive agents or phototherapy not established.1 Do not use concurrently with other immunosuppressive agents (due to possible increased risk of infections and malignancies).1

Immunization

Review vaccination status and administer all age-appropriate vaccines prior to initiation of efalizumab.1 Do not administer live or live-attenuated vaccines during efalizumab therapy.1 Caution patients about potential risk of shedding and transmission if household contacts receive live vaccines.1

First-dose Reactions

Reactions (e.g., headache, fever, nausea, vomiting) may occur following the first dose of efalizumab; incidence and severity of these reactions are dose related.1 A reduced initial dose (0.7 mg/kg) is recommended to decrease the incidence and severity of these reactions.1

Antibody Formation

Possible development of predominantly low-titer antibodies to efalizumab or other protein components of the preparation.1 Long-term immunogenicity remains to be determined.1

Specific Populations

Pregnancy

Category C.1

Pregnancy registry at 877-727-8482.1

Lactation

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

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 10 Potential risk of non-recoverable suppression of humoral immunity observed following repeated administration of anti-mouse CD11a antibody, a murine surrogate for efalizumab, in juvenile mice.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but experience is insufficient to exclude important differences in response.1 Use with caution due to increased incidence of infections in geriatric individuals.1

Hepatic Impairment

Pharmacokinetics not evaluated.1 10

Renal Impairment

Pharmacokinetics not evaluated.1 10

Common Adverse Effects

Headache, infection, chills, fever, nausea, myalgia, pain, flu syndrome, back pain, acne.1

Interactions for Raptiva

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Comments

Immunosuppressive agents

Possible excessive immunosuppression1

Concomitant use not recommended1

Vaccines

Possible inadequate immune response to inactivated vaccines1

Concomitant use with live or live-attenuated vaccines not recommended1 (see Immunization under Cautions)

Raptiva Pharmacokinetics

Absorption

Bioavailability

Bioavailability after sub-Q administration is 50%.1

Steady-state serum concentrations are reached after 4 weeks of therapy at recommended dosage.1 6

Elimination

Half-life

Mean time for concentrations to decrease to undetectable levels following discontinuance: 25 days.1 6

Stability

Storage

Parenteral

For Injection, for sub-Q use

Powder: 2–8°C; do not freeze or store at room temperature.1

Reconstituted solutions: room temperature for up to 8 hours.1

Protect from light; store in original carton until administration.1

Actions

  • Binds to human CD11a, the α subunit of leukocyte function-associated antigen 1 (LFA-1), which is expressed on leukocytes, and decreases cell surface expression of CD11a.1 2 6 7

  • Inhibits the binding of LFA-1 to intercellular adhesion molecule (ICAM-1), thereby inhibiting the adhesion of leukocytes to other cell types.1 6 7 Interaction between LFA-1 and ICAM-1 contributes to initiation and maintenance of multiple processes, including activation of T cells, adhesion of T cells to endothelial cells, and migration of T cells to sites of inflammation.1 2

  • May affect activation, adhesion, migration, and numbers of cells other than T cells, since CD11a also is expressed on the surface of B cells, monocytes, neutrophils, natural killer cells, and other leukocytes.1

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Provide a copy of the manufacturer’s patient information.1

  • Possible increased risk of malignancy or serious, potentially fatal infection.1 Importance of informing clinicians promptly of any signs or new diagnosis of infection (including PML) or malignancy.1

  • Potential for adverse nervous system effects.1 Importance of immediately informing clinicians and/or seeking immediate medical attention if adverse nervous system effects (e.g., sudden onset of numbness or tingling; weakness in arms, legs, or face; new or sudden change in thinking, balance, strength, talking, walking, or vision) occur.1

  • Potential for reduction of platelet counts; advise patients that clinicians may monitor platelet counts.1 Importance of promptly reporting any signs or symptoms of severe thrombocytopenia (e.g., easy bleeding from gums, bruising, petechiae).1

  • Potential for hemolytic anemia.1 Importance of informing clinicians promptly if any signs or symptoms of severe hemolytic anemia (e.g., weakness, orthostatic light-headedness, dark or red urine, jaundice) occur.1

  • Potential for worsening of psoriasis and/or arthritis.1 Importance of informing clinicians promptly if any signs or symptoms of worsening of psoriasis (e.g., new rashes) or arthritis (e.g., redness, pain, swelling, or stiffness of joints) occur.1

  • Importance of receiving all age-appropriate vaccines prior to initiation of efalizumab therapy and of avoiding live or live-attenuated vaccines during therapy.1 Importance of informing clinicians of household contacts requiring live or live-attenuated vaccines (because of the risk for shedding and transmission).1

  • If patient or caregiver is to administer efalizumab, provide careful instruction on proper administration methods.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed during or within 6 weeks following discontinuance of efalizumab therapy.1 Importance of clinicians informing women about the existence of and encouraging enrollment in pregnancy registry.1 (See Pregnancy under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as 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.

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Efalizumab (Recombinant)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use

125 mg

Raptiva

Genentech

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2010, Selected Revisions August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Genentech, Inc. Raptiva (efalizumab) for injection prescribing information. South San Francisco, CA; 2008 Oct 16.

2. Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003; 49(2 Suppl):S98-104. [IDIS 503046] [PubMed 12894132]

3. Gordon KB, Papp KA, Hamilton TK et al. Efalizumab for patients with moderate to severe plaque psoriasis. JAMA. 2003; 290:3073-80. [IDIS 508678] [PubMed 14679270]

4. Lebwohl M, Tyring SK, Hamilton TK et al. novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med. 2003; 349:2004-13. [IDIS 507152] [PubMed 14627785]

5. Anon. Efalizumab (Raptiva) for treatment of psoriasis. Med Lett Drugs Ther. 2003; 45:97-8. [PubMed 14657802]

6. Tam JW, Lee GJ, Song JC. Efalizumab: a new biologic therapy for the control of chronic plaque psoriasis. Formulary. 2004; 39:20-39.

7. Weinberg JM. An overview of infliximab, etanercept, efalizumab, and alefacept as biologic therapy for psoriasis. Clin Ther. 2003; 25:2487-505. [IDIS 506815] [PubMed 14667953]

8. Menter A, Kardatzke D, Rundle AC et al. Incidence and prevention of rebound upon efalizumab discontinuation. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 34.

9. Carey W, Rundle AC, Kwon P et al. Taper regimens in the management of patients discontinuing efalizumab therapy. Presented at: 10th International Psoriasis Symposium™ 2004; June 10-13, 2004; Toronto, Canada. Poster 29.

10. Genentech, South San Francisco, CA: Personal communication.

11. Barron H. Dear health care professional letter: Important drug warning regarding Raptiva (efalizumab). South San Francisco, CA: Genentech; 2005 Jul.

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