Alefacept

Name: Alefacept

Do I need a prescription for alefacept?

Yes

Warnings

Included as part of the PRECAUTIONS section.

Inform MD

Before starting alefacept, tell your doctor if you think you have an infection or have symptoms of an infection such as:

  • swollen glands.
  • fever, sweats or chills.
  • cough.
  • muscle aches.
  • shortness of breath.
  • blood in your phlegm.
  • warm, red, or painful skin or sores on your body.
  • burning when you urinate or urinate more often than normal.
  • feel very tired.
  • get a lot of infections or have infections that keep coming back.

After starting alefacept, call your doctor right away if you have any symptoms of an infection (see above).

Before receiving alefacept, tell your doctor if you:

  • are receiving phototherapy for your psoriasis.
  • are allergic to alefacept or any of its ingredients. See "Forms of Medication."
  • have any other medical conditions.
  • are pregnant or plan to become pregnant. It is not known if alefacept will harm your unborn baby. Tell your doctor right away if you become pregnant while receiving alefacept or within 8 weeks after receiving your last dose of alefacept.
  • are breastfeeding or plan to breastfeed. It is not known if alefacept passes into your breast milk. You and your doctor should decide if you will take alefacept or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Especially tell your doctor if you receive phototherapy or take any other medicines that affect your immune system, including other medicines for treatment of your plaque psoriasis.

 

Alefacept Overdose

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Other Requirements

Keep all medical and laboratory appointments. It is important that you receive alefacept on schedule to get the most benefit. During treatment, your doctor will ask that you have blood tests to monitor progress and side effects. It is important to have regular monitoring of white blood cell (lymphocyte) counts during therapy with alefacept. The reduction in lymphocytes could increase your chances of developing an infection or a malignancy. 

Pregnancy & Lactation

Pregnancy Category: B

Lactation: excretion in milk unknown/not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

Side effects

The most serious adverse reactions described elsewhere in the labeling include the following:

  • Lymphopenia [see WARNINGS AND PRECAUTIONS]
  • Malignancies [see WARNINGS AND PRECAUTIONS]
  • Serious Infections requiring hospitalization [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Commonly observed adverse events seen in the first course of placebo-controlled clinical trials with at least a 2% higher incidence in the AMEVIVE®-treated patients compared to placebo-treated patients were: pharyngitis, dizziness, increased cough, nausea, pruritus, myalgia, chills, injection site pain, injection site inflammation, and accidental injury. The only adverse event that occurred at a 5% or higher incidence among AMEVIVE®-treated patients compared to placebo-treated patients was chills (1% placebo vs. 6% AMEVIVE®), which occurred predominantly with intravenous administration.

The adverse reactions which most commonly resulted in clinical intervention were cardiovascular events including coronary artery disorder in < 1% of subjects and myocardial infarct in < 1% of subjects. These events were not observed in any of the 413 placebo-treated subjects. The total number of subjects hospitalized for cardiovascular events in the AMEVIVE®-treated group was 1.2% (11/876).

The most common events resulting in discontinuation of treatment with AMEVIVE® were CD4+ T lymphocyte levels below 250 cells/µL [see WARNINGS AND PRECAUTIONS], headache (0.2%), and nausea (0.2%).

The data described below reflect exposure to AMEVIVE® in a total of 1869 psoriasis patients, of whom 1315 (70%) received 1 to 2 courses of therapy and 554 (30%) received 3 or more courses. The median duration of follow-up was 8.4 months for the patients who received 1 to 2 courses and 27.7 months for the patients who received 3 or more courses of AMEVIVE®. Of the 1869 total patients, 876 received their first course in placebo-controlled studies. The population studied ranged in age from 16 to 84 years, and included 69% men and 31% women. The patients were mostly Caucasian (88%), reflecting the general psoriatic population. Disease severity at baseline was moderate to severe psoriasis.

Effect on Lymphocyte Counts

In the intramuscular study (Study 2), 4% of patients temporarily discontinued treatment and no patients permanently discontinued treatment due to CD4+ T lymphocyte counts below the specified threshold of 250 cells/µL. In Study 2, 10%, 28%, and 42% of patients had total lymphocyte, CD4+, and CD8+ T lymphocyte counts below normal, respectively. Twelve weeks after a course of therapy (12 weekly doses), 2%, 8%, and 21% of patients had total lymphocyte, CD4+, and CD8+ T cell counts below normal.

In the first course of the intravenous study (Study 1), 10% of patients temporarily discontinued treatment and 2% permanently discontinued treatment due to CD4+ T lymphocyte counts below the specified threshold of 250 cells/µL. During the first course of Study 1,22% of patients had total lymphocyte counts below normal, 48% had CD4+ T lymphocyte counts below normal and 59% had CD8+ T lymphocyte counts below normal. The maximal effect on lymphocytes was observed within 6 to 8 weeks of initiation of treatment. Twelve weeks after a course of therapy (12 weekly doses), 4% of patients had total lymphocyte counts below normal, 19% had CD4+ T lymphocyte counts below normal, and 36% had CD8+ T lymphocyte counts below normal.

For patients receiving a second course of AMEVIVE® in Study 1,17% of patients had total lymphocyte counts below normal, 44% had CD4+ T lymphocyte counts below normal, and 56% had CD8+ T lymphocyte counts below normal. Twelve weeks after completing dosing, 3% of patients had total lymphocyte counts below normal, 17% had CD4+ T lymphocyte counts below normal, and 35% had CD8+ T lymphocyte counts below normal [see WARNINGS AND PRECAUTIONS].

In an open-label postmarketing study, subjects with psoriasis were treated with up to three courses of Amevive: each course consisted of Amevive 15 mg intramuscular weekly for twelve weeks, followed by twelve weeks of observation. Lymphocyte counts were assessed at regular intervals during the post-treatment observation period. For subjects whose counts went below 75% of the baseline at any time after the last dose in the study, the time from the last dose to the time that their lymphocyte count returned to ≥ 75% of baseline was analyzed. Of 115 evaluable subjects for total lymphocyte counts, the median time of recovery was 2.1 months with a range of 0.6 to 11.1 months. Of the 123 evaluable subjects for CD4+ T cell counts, the median time to recovery was 2.3 months with the range of 0.6 to 12.4 months. Of the 105 evaluable subjects for CD8+ T cell counts, the median time to recovery was 1.6 months with a range of 0.6 to 8.7 months.

Malignancies

In the 24-week period constituting the first course of placebo-controlled studies, 13 malignancies were diagnosed in 11 AMEVIVE®-treated patients. The incidence of malignancies was 1.3% (11/876) for AMEVIVE®-treated patients compared to 0.5% (2/413) in the placebo group.

Among 1869 patients who received AMEVIVE® at any dose in clinical trials, 43 patients were diagnosed with 63 treatment-emergent malignancies. The majority of the malignancies were non-melanoma skin cancers: 46 cases (20 basal cell, 26 squamous cell carcinomas) in 27 patients. Other malignancies observed in AMEVIVE®-treated patients included melanoma (n=3), solid organ malignancies (n=12 in 11 patients), and lymphomas (n=5); the latter consisted of two Hodgkin's and two non-Hodgkin's lymphomas, and one cutaneous T cell lymphoma (mycosis fungoides).

Infections

In the 24-week period constituting the first course of placebo-controlled studies, serious infections (infections requiring hospitalization) were seen at a rate of 0.9% (8/876) in AMEVIVE®-treated patients and 0.2% (1/413) in the placebo group. In patients receiving repeated courses of AMEVIVE® therapy, the rates of serious infections remained similar across courses of therapy. Serious infections among 1869 AMEVIVE®-treated patients included cellulitis, abscesses, wound infections, toxic shock, pneumonia, appendicitis, cholecystitis, gastroenteritis and herpes infections.

Hypersensitivity Reactions

In clinical studies, 4 of 1869 (0.2%) patients were reported to experience angioedema: two of these patients were hospitalized. In the 24-week period constituting the first course of placebo-controlled studies, urticaria was reported in 6 ( < 1%) AMEVrVE®-treated patients vs. 1 patient in the control group. Urticaria resulted in discontinuation of therapy in one of the AMEVIVE®-treated patients.

Hepatic Injury

In the 24-week period constituting the first course of placebo-controlled studies, 1.7% (15/876) of AMEVIVE®-treated patients and 1.2% (5/413) of the placebo group experienced ALT and/or AST elevations of at least 3 times the upper limit of normal.

Injection Site Reactions

In the intramuscular study (Study 2), 16% of AMEVIVE®-treated patients and 8% of placebo-treated patients reported injection site reactions. In patients receiving repeated courses of AMEVIVE® intramuscular therapy, the incidence of injection site reactions remained similar across courses of therapy. Reactions at the site of injection were generally mild, typically occurred on single occasions, and included either pain (7%), inflammation (4%), bleeding (4%), edema (2%), non-specific reaction (2%), mass (1%), or skin hypersensitivity ( < 1%). In the clinical trials, a single case of injection site reaction led to the discontinuation of AMEVIVE®.

Immunogenicity

Approximately 3% (40/1357) of patients receiving AMEVIVE® developed low-titer antibodies to alefacept as determined by an ELISA. When anti-alefacept antibodies were assessed using a dual specificity Biacore assay, 72% (72/100) of patients receiving AMEVIVE® were positive for anti-alefacept antibodies. The long-term immunogenicity of AMEVIVE® is unknown.

Results are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to alefacept with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of AMEVIVE. Because these reactions are reported voluntary from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Malignancies

In post-marketing experience there have been reports of malignancies including skin, solid organ, lymphomas and leukemias [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Serious Infections

In post-marketing experience there have been reports of infections including sepsis, opportunistic infections (viral, fungal, bacterial), cellulitis, urinary tract infection (UTI), Clostridium difficile colitis and pharyngitis [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Hepatic Injury

In post-marketing experience there have been reports of asymptomatic transaminase elevation, fatty infiltration of the liver, hepatitis, and severe liver failure [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Read the entire FDA prescribing information for Amevive (Alefacept)

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