Leflunomide

Trade Names:
Arava
- Tablet 10 mg
- Tablet 20 mg

Pharmacology

User Reviews & Ratings As a treatment for... Avg User Ratings [?] Rheumatoid Arthritis 5 reviews Rate it! 5.8 Compare with other drugs.

An isoxazole immunomodulatory agent that inhibits dihydro-orotate dehydrogenase and has antiproliferative and anti-inflammatory activity.

Pharmacokinetics

Absorption

The T _max of active metabolite is 6 to 12 h. Without a loading dose (100 mg/3 days), steady-state plasma concentration would require nearly 2 mo of dosing. Plasma levels are dose-proportional. High-fat food does not affect absorption.

Distribution

Steady-state Vd is 0.13 L/kg. Greater than 99.3% protein bound.

Metabolism

The specific site of metabolism is unknown. The major active metabolite responsible for all activity is A77 1726 (M1); 4-trifluor-methylaniline is the minor metabolite.

Elimination

The t _½ is approximately 2 wk. Renally excreted as well as by direct biliary excretion. Renal excretion is more significant in the first 96 h. Eliminated in urine (43%) and feces (48%). Primary urinary metabolites are leflunomide glucoronide and oxanilic acid derivative of M1. Primary fecal metabolite is M1.

Special Populations

Studies have not been done; however, leflunomide is not recommended in these patients.

Tobacco use has a 38% increase in Cl over nonsmokers; however, no difference in clinical efficacy was seen between smokers and nonsmokers.

Indications and Usage

Treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms and to retard structural damage.

Contraindications

Pregnancy; standard considerations.

Dosage and Administration

PO 100 mg every day for 3 days.

PO 20 mg every day. If dosing at 20 mg/day is not well-tolerated, the dose may be decreased to 10 mg/day.

General Advice

• Administer without regard to meals. Administer with food if GI upset occurs.
• Do not administer until baseline liver enzymes have been evaluated.

Storage/Stability

Store at controlled room temperature (59° to 86°F); protect from light.

Drug Interactions

Decrease plasma leflunomide.

May potentiate the hepatotoxicity of leflunomide.

Free-fraction serum concentrations were increased by leflunomide.

May increase leflunomide serum levels.

Laboratory Test Interactions

May cause hypophosphaturia. May cause an increase in uric acid excretion.

Adverse Reactions

Cardiovascular

Hypertension; chest pain; palpitation; tachycardia; varicose vein; vasculitis; vasodilation.

CNS

Dizziness; headache; paresthesia; anxiety; depression; dry mouth; insomnia; neuralgia; neuritis; sleep disorder; vertigo; migraine.

Dermatologic

Alopecia; eczema; pruritus; rash; dry skin; abscess; cyst; Stevens-Johnson syndrome and toxic epidermal necrolysis (rare, discontinue drug if symptoms occur).

Endocrine

Diabetes mellitus; hyperthyroidism.

GI

Abdominal pain; anorexia; diarrhea; dyspepsia; gastroenteritis; nausea; mouth ulcer; vomiting.

Genitourinary

Albuminuria; cystitis; dysuria; hematuria; menstrual disorder; prostate disorder; urinary frequency; vaginal moniliasis.

Hematologic-Lymphatic

Anemia; ecchymosis.

Hepatic

Abnormal liver enzymes.

Hypersensitivity

Allergic reaction.

Metabolic-Nutritional

Increased CPK; hyperglycemia; hyperlipidemia; hypokalemia.

Musculoskeletal

Arthralgia; leg cramps; joint disorder; synovitis; tenosynovitis; arthrosis; bone necrosis; bone pain; bursitis; muscle cramps; myalgia; tendon rupture.

Respiratory

Bronchitis; increased cough; respiratory infection; pharyngitis; pneumonia; rhinitis; sinusitis; asthma; dyspnea; epistaxis; lung disorder.

Special Senses

Blurred vision; cataract; conjunctivitis; eye disorder; taste perversion.

Miscellaneous

Peripheral edema; weight loss; UTI; asthenia; flu syndrome; infection; injury, accident; pain; back pain; fever; hernia; malaise; neck pain; pelvic pain; increased sweating.

Precautions

Pregnancy

Category X .

Lactation

Do not use in breast-feeding mothers. It is not known if leflunomide is excreted in human milk.

Children

Not established.

Elderly

No dosage adjustment is needed in patients older than 65 yr of age.

Special Risk Patients

Renal function impairment; immunocompromise; bone marrow dysplasia; severe, uncontrolled infections; pre-existing hepatic disease.

Drug elimination procedure

Without the drug elimination procedure, it may take up to 2 yr to reach plasma M1 metabolite levels less than 0.02 mg/L because of individual variation in drug Cl. Recommended to achieve nondetectable plasma levels (less than 0.02 mg/L) after stopping treatment:

• Administer cholestyramine 8 g 3 times daily for 11 days. (The 11 days do not need to be consecutive unless there is a need to lower the plasma level rapidly.)
• Verify plasma levels less than 0.02 mg/L by 2 separate tests at least 14 days apart. If plasma levels are more than 0.02 mg/L, consider additional cholestyramine treatment.

Patient Information

• Review usual dosing schedule with patient: 100 mg daily for 3 days (loading dose) then 20 mg daily for maintenance. Warn patient that taking more of the drug than prescribed can result in serious adverse reactions, including liver damage.
• Advise patient that drug may be taken without regard to meals.
• Remind patient that other medications for RA may still be taken while taking this drug.
• Advise women that this drug may cause birth defects.
• Advise women to use effective contraception during treatment and not to attempt to become pregnant after stopping the drug until they have gone through the drug elimination procedure.
• Advise men wishing to father a child not to do so unless they have stopped the drug and have taken cholestyramine (part of drug elimination procedure) for 11 days.
• Advise patient to avoid live vaccines while taking this drug.
• Advise patient that diarrhea, nausea, indigestion, and headache are common adverse reactions and to inform health care provider if they occur and are intolerable.

Link to Page

Print Page

Email Page

Add to List