leflunomide

leflunomide /le·flu·no·mide/ (lĕ-floo´no-mīd) an immunomodulator used in treatment of rheumatoid arthritis.

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leflunomide,

a pyrimidine synthesis inhibitor with anti-inflammatory effects.

indications It is used to treat rheumatoid arthritis.

contraindications Pregnancy, lactation, hepatic disease, jaundice, positive hepatitis B and C, severe immunosuppression, and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects include chest pain, angina pectoris, migraine, bronchitis, cough, respiratory infection, pneumonia, and sinusitis. Common side effects include nausea, anorexia, vomiting, constipation, flatulence, dizziness, insomnia, depression, paresthesia, palpitations, hypertension, rash, pruritus, pharyngitis, and rhinitis.

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leflunomide Warning - Hazardous drug!

Arava

Pharmacologic class: Immune modulator

Therapeutic class: Antirheumatic

Pregnancy risk category X

FDA Boxed Warning

• Rule out pregnancy before starting therapy. Drug is contraindicated in pregnant women and in women of childbearing age who don't use reliable contraception. Caution patient to avoid pregnancy during therapy or before completing drug elimination procedure after treatment.

Action

Inhibits T-cell pyrimidine biosynthesis, tyrosine kinases, and dihydroorotate dehydrogenase, blocking structural damage caused by inflammatory response to autoimmune process. Also shows analgesic, antipyretic, and histamine-blocking activity.

Availability

Tablets: 10 mg, 20 mg

⊘Indications and dosages

➣ Active rheumatoid arthritis

Adults: 100 mg P.O. daily for 3 days, then a maintenance dosage of 20 mg daily. If intolerance occurs, decrease to 10 mg daily.

Dosage adjustment

• Hepatic enzyme elevations

Contraindications

• Hypersensitivity to drug or its components
• Immunocompromised state, including bone marrow dysplasia and severe uncontrolled infection
• Hepatic impairment, evidence of hepatitis B or C
• Live-virus vaccinations
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• renal insufficiency
• men attempting to father a child
• children younger than age 18.

Administration

• Give with or without food.
• Be aware that drug has a long half-life. To eliminate from bloodstream, give 8 g cholestyramine P.O. t.i.d. for 11 days.

Route	Onset	Peak	Duration
P.O.	1 mo	3-6 mo	Unknown

Adverse reactions

CNS: headache, dizziness, asthenia

CV: chest pain, hypertension

EENT: rhinitis, sinusitis, pharyngitis

GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia, gastroenteritis, mouth ulcers, anorexia

GU: urinary tract infection

Hepatic: hepatotoxicity

Metabolic: hypokalemia

Musculoskeletal: joint pain or disorders, back pain, leg cramps, synovitis, tenosynovitis

Respiratory: bronchitis, increased cough, pneumonia, respiratory infection

Skin: alopecia, rash, dry skin, eczema, pruritus

Other: weight loss, pain, infection, allergic reactions, flulike symptoms

Interactions

Drug-drug. Activated charcoal, cholestyramine: rapid, steep drop in blood level of leflunomide's active metabolite

Methotrexate, other hepatotoxic drugs: increased risk of hepatotoxicity

Rifampin: increased blood level of leflunomide's active metabolite

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: increased levels

Patient monitoring

• Check vital signs closely.
☞ Watch for signs and symptoms of hepatotoxicity.
• Assess cardiovascular and respiratory status carefully to detect adverse reactions.
• Monitor electrolyte levels and liver function tests.
• Stay alert for signs and symptoms of urinary tract infection.
• Observe patient closely after dosage reduction. Metabolite levels may take several weeks to fall.

Patient teaching

• Tell patient he may take with or without food.
☞ Advise patient to immediately report unusual tiredness or yellowing of skin or eyes.
• Tell patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
☞ Inform female of childbearing age that drug may harm fetus. Tell her to contact prescriber immediately if she suspects pregnancy.
• Caution female not to breastfeed without consulting prescriber.
• Advise male planning to father a child to consult prescriber, because drug can harm fetus.
• Tell patient he'll undergo regular blood testing to check liver function.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.