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Amevive (Alefacept) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The most serious adverse reactions were:

  

  • Lymphopenia (see WARNINGS)
  • Malignancies (see WARNINGS)
  • Serious Infections requiring hospitalization (see WARNINGS)
  • Hypersensitivity Reactions (see PRECAUTIONS, Allergic Reactions)

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 patients and myocardial infarct in <1% of patients. These events were not observed in any of the 413 placebo-treated patients. The total number of patients 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 ADVERSE REACTIONS, Effect on Lymphocyte Counts), headache (0.2%), and nausea (0.2%).

Because clinical trials are conducted under widely varying conditions, adverse event 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. The adverse reaction information does, however, provide a basis for identifying the adverse events that appear to be related to drug use and a basis for approximating rates.

The data described below reflect exposure to AMEVIVE® in a total of 1357 psoriasis patients, 85% of whom received 1 to 2 courses of therapy and the rest received 3 to 6 courses and were followed for up to three years. Of the 1357 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 (89%), 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, Laboratory Tests).

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 1357 patients who received AMEVIVE® , 25 patients were diagnosed with 35 treatment-emergent malignancies. The majority of these malignancies (23 cases) were basal (6) or squamous cell cancers (17) of the skin. Three cases of lymphoma were observed; one was classified as non-Hodgkin's follicle-center cell lymphoma and two were classified as Hodgkin's disease.

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 were 0.7% (5/756) and 1.5% (3/199) in the second and third course of therapy, respectively. Serious infections among 1357 AMEVIVE® -treated patients included necrotizing cellulitis, peritonsillar abscess, post-operative and burn woundinfection, toxic shock, pneumonia, appendicitis, pre-septal cellulitis, cholecystitis, gastroenteritis and herpes simplex infection.

HYPERSENSITIVITY REACTIONS

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

HEPATIC EVENTS

In post-marketing surveillance hepatic events, including a case of hepatitis associated with transient coagulopathy and hyperbilirubinemia, have been reported.

INJECTION SITE REACTIONS

In the intramuscular study (Study 2), 16% of AMEVIVE® -treated patients and 8% of placebo-treated patients reported injection site reactions. 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% (35/1306) of patients receiving AMEVIVE® developed low-titer antibodies to alefacept. No apparent correlation of antibody development and clinical response or adverse events was observed. The long-term immunogenicity of AMEVIVE® is unknown.

The data reflect the percentage of patients whose test results were considered positive for antibodies to alefacept in an ELISA assay, and 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.

OTHER OBSERVED ADVERSE REACTIONS FROM CLINICAL TRIALS

Less common events that were observed at a higher rate in AMEVIVE® -treated patients include rare cases (9) of transaminase elevations to 5 to 10 times the upper limit ofnormal.



REPORTS OF SUSPECTED AMEVIVE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Amevive. The information is not vetted and should not be considered as verified clinical evidence.

Possible Amevive side effects / adverse reactions in 49 year old male

Reported by a health professional (non-physician/pharmacist) from Canada on 2011-10-17

Patient: 49 year old male weighing 77.0 kg (169.4 pounds)

Reactions: Diabetes Mellitus

Suspect drug(s):
Amevive



Possible Amevive side effects / adverse reactions in 49 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-31

Patient: 49 year old male weighing 56.0 kg (123.2 pounds)

Reactions: OFF Label USE, Gastroenteritis, Kidney Transplant Rejection

Adverse event resulted in: hospitalization

Suspect drug(s):
Amevive
    Dosage: 15 mg, monthly
    End date: 2011-02-10

Amevive
    Dosage: 7.5 mg, pod 0 + 2
    Indication: Renal Transplant
    Start date: 2010-11-19

Amevive
    Dosage: 15 mg, weekly x 12 weeks

Other drugs received by patient: Myfortic; Clotrimazole; Valcyte; Norvasc; Levothyroxine Sodium; Bactrim DS; Lopressor; Aspirin; Synthroid; Plavix; Tricor; Metoprolol



Possible Amevive side effects / adverse reactions in 57 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2011-11-10

Patient: 57 year old male weighing 85.0 kg (187.0 pounds)

Reactions: Klebsiella Infection, Ultrasound Scan Abnormal, Pneumonia, Cellulitis, Blastomycosis, Abscess

Adverse event resulted in: hospitalization

Suspect drug(s):
Prograf
    Dosage: 1 mg, q12 hours
    Indication: Product Used FOR Unknown Indication

Amevive
    Dosage: 15 mg, weekly
    Indication: Renal Transplant
    Start date: 2010-11-19
    End date: 2011-02-10



See index of all Amevive side effect reports >>

Drug label data at the top of this Page last updated: 2006-08-08

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