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Arava (Leflunomide) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Adverse reactions associated with the use of leflunomide in RA include diarrhea, elevated liver enzymes (ALT and AST), alopecia and rash. In the controlled studies at one year, the following adverse events were reported, regardless of causality. (See Table 9.)

Table 9. Percentage Of Patients With Adverse Events ≥3% In Any Leflunomide Treated Group
All RA StudiesPlacebo-Controlled TrialsActive-Controlled Trials
MN 301 and US 301MN 302Only 10% of patients in MN302 received folate. All patients in US301 received folate; none in MN301 received folate.
LEF
(N=1339)Includes all controlled and uncontrolled trials with leflunomide (duration up to 12 months).
LEF
(N=315)
PBO
(N=210)
SSZ
(N=133)
MTX
(N=182)
LEF
(N=501)
MTX
(N=498)
BODY AS A WHOLE
Allergic Reaction2%5%2%0%6%1%2%
Asthenia3%6%4%5%6%3%3%
Flu Syndrome2%4%2%0%7%0%0%
Infection, upper respiratory4%0%0%0%0%0%0%
Injury Accident5%7%5%3%11%6%7%
Pain2%4%2%2%5%1%<1%
Abdominal Pain6%5%4%4%8%6%4%
Back Pain5%6%3%4%9%8%7%
CARDIOVASCULAR
HypertensionHypertension as a preexisting condition was overrepresented in all leflunomide treatment groups in phase III trials 10%9%4%4%3%10%4%
- New onset of hypertension1%<1%0%2%2%<1%
Chest Pain2%4%2%2%4%1%2%
GASTROINTESTINAL
Anorexia3%3%2%5%2%3%3%
Diarrhea17%27%12%10%20%22%10%
Dyspepsia5%10%10%9%13%6%7%
Gastroenteritis3%1%1%0%6%3%3%
Abnormal Liver Enzymes5%10%2%4%10%6%17%
Nausea9%13%11%19%18%13%18%
GI/Abdominal Pain5%6%4%7%8%8%8%
Mouth Ulcer3%5%4%3%10%3%6%
Vomiting3%5%4%4%3%3%3%
METABOLIC AND NUTRITIONAL
Hypokalemia1%3%1%1%1%1%<1%
Weight LossIn a meta-analysis of all phase II and III studies, during the first 6 months in patients receiving leflunomide, 10% lost 10–19 lbs (24 cases per 100 patient years) and 2% lost at least 20 lbs (4 cases/100 patient years). Of patients receiving leflunomide, 4% lost 10% of their baseline weight during the first 6 months of treatment.4%2%1%2%0%2%2%
MUSCULO-SKELETAL SYSTEM
Arthralgia1%4%3%0%9%<1%1%
Leg Cramps1%4%2%2%6%0%0%
Joint Disorder4%2%2%2%2%8%6%
Synovitis2%<1%1%0%2%4%2%
Tenosynovitis3%2%0%1%2%5%1%
NERVOUS SYSTEM
Dizziness4%5%3%6%5%7%6%
Headache7%13%11%12%21%10%8%
Paresthesia2%3%1%1%2%4%3%
RESPIRATORY SYSTEM
Bronchitis7%5%2%4%7%8%7%
Increased Cough3%4%5%3%6%5%7%
Respiratory Infection15%21%21%20%32%27%25%
Pharyngitis3%2%1%2%1%3%3%
Pneumonia2%3%0%0%1%2%2%
Rhinitis2%5%2%4%3%2%2%
Sinusitis2%5%5%0%10%1%1%
SKIN AND APPENDAGES
Alopecia10%9%1%6%6%17%10%
Eczema2%1%1%1%1%3%2%
Pruritus4%5%2%3%2%6%2%
Rash10%12%7%11%9%11%10%
Dry Skin2%3%2%2%0%3%1%
UROGENITAL SYSTEM
Urinary Tract Infection5%5%7%4%2%5%6%

Adverse events during a second year of treatment with leflunomide in clinical trials were consistent with those observed during the first year of treatment and occurred at a similar or lower incidence.

In addition, the following adverse events have been reported in 1% to <3% of the RA patients in the leflunomide treatment group in controlled clinical trials.

Body as a Whole: abscess, cyst, fever, hernia, malaise, pain, neck pain, pelvic pain;

Cardiovascular: angina pectoris, migraine, palpitation, tachycardia, varicose vein, vasculitis, vasodilatation;

Gastrointestinal: cholelithiasis, colitis, constipation, esophagitis, flatulence, gastritis, gingivitis, melena, oral moniliasis, pharyngitis, salivary gland enlarged, stomatitis (or aphthous stomatitis), tooth disorder;

Endocrine: diabetes mellitus, hyperthyroidism;

Hemic and Lymphatic System: anemia (including iron deficiency anemia), ecchymosis;

Metabolic and Nutritional: creatine phosphokinase increased, hyperglycemia, hyperlipidemia, peripheral edema;

Musculo-Skeletal System: arthrosis, bone necrosis, bone pain, bursitis, muscle cramps, myalgia, tendon rupture;

Nervous System: anxiety, depression, dry mouth, insomnia, neuralgia, neuritis, sleep disorder, sweating increased, vertigo;

Respiratory System: asthma, dyspnea, epistaxis, lung disorder;

Skin and Appendages: acne, contact dermatitis, fungal dermatitis, hair discoloration, hematoma, herpes simplex, herpes zoster, maculopapular rash, nail disorder, skin discoloration, skin disorder, skin nodule, subcutaneous nodule, ulcer skin;

Special Senses: blurred vision, cataract, conjunctivitis, eye disorder, taste perversion;

Urogenital System: albuminuria, cystitis, dysuria, hematuria, menstrual disorder, prostate disorder, urinary frequency, vaginal moniliasis.

Other less common adverse events seen in clinical trials include: 1 case of anaphylactic reaction occurred in Phase 2 following rechallenge of drug after withdrawal due to rash (rare); urticaria; eosinophilia; transient thrombocytopenia (rare); and leukopenia <2000 WBC/mm3 (rare).

Adverse events during a second year of treatment with leflunomide in clinical trials were consistent with those observed during the first year of treatment and occurred at a similar or lower incidence.

In post-marketing experience, the following have been reported rarely:

Body as a Whole: opportunistic infections, severe infections including sepsis that may be fatal;

Gastrointestinal: pancreatitis;

Hematologic: agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia

Hypersensitivity: angioedema;

Hepatic: hepatitis, jaundice/cholestasis, severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal;

Respiratory: interstitial lung disease, including interstitial pneumonitis and pulmonary fibrosis, which may be fatal;

Nervous System: peripheral neuropathy;

Skin and Appendages: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis including cutaneous necrotizing vasculitis.

Adverse Reactions (Pediatric Patients)

The safety of ARAVA was studied in 74 patients with polyarticular course juvenile rheumatoid arthritis ranging in age from 3–17 years (47 patients from the active-controlled study and 27 from an open-label safety and pharmacokinetic study). The most common adverse events included abdominal pain, diarrhea, nausea, vomiting, oral ulcers, upper respiratory tract infections, alopecia, rash, headache, and dizziness. Less common adverse events included anemia, hypertension, and weight loss. Fourteen pediatric patients experienced ALT and/or AST elevations, nine between 1.2 and 3-fold the upper limit of normal, five between 3 and 8-fold the upper limit of normal.



REPORTS OF SUSPECTED ARAVA SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Arava side effects / adverse reactions in 62 year old male

Reported by a health professional (non-physician/pharmacist) from Switzerland on 2011-10-03

Patient: 62 year old male weighing 85.0 kg (187.0 pounds)

Reactions: Megakaryocytes Abnormal, Bone Marrow Failure, Normochromic Normocytic Anaemia, Lymphoma

Suspect drug(s):
Etanercept
    Indication: Psoriatic Arthropathy
    Start date: 2007-11-01

Arava
    Administration route: Oral
    Indication: Psoriatic Arthropathy
    Start date: 2003-06-01

Other drugs received by patient: Duragesic-100; Motilium; Prednisolone; Calcimagon-D3; Lisinopril; Lisinopril; Acetaminophen; Amlodipine



Possible Arava side effects / adverse reactions in 72 year old male

Reported by a physician from France on 2011-10-04

Patient: 72 year old male

Reactions: Blood Creatinine Increased, Septic Shock, Renal Failure Chronic, Pyelonephritis, Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):
Arava

Other drugs received by patient: Androcur; Lansoprazole; Clorazepate Dipotassium; Lasix; Ramipril; Epogen; Atorvastatin Calcium; Aspirin; Zopiclone; Prednisone; Azopt; Allopurinol



Possible Arava side effects / adverse reactions in 75 year old male

Reported by a consumer/non-health professional from Australia on 2011-10-04

Patient: 75 year old male

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Arava

Other drugs received by patient: Avapro; Nitroglycerin; Aspirin; Prednisone



See index of all Arava side effect reports >>

Drug label data at the top of this Page last updated: 2007-11-15

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