leflunomide

Contraindicated in:

Hypersensitivity to leflunomide or teriflunomide;
Compromised immune function, including bone marrow dysplasia or severe uncontrolled infection;
Concurrent vaccination with live vaccines;
Severe hepatic impairment, pre-existing acute or chronic liver disease, or ALT >2 times upper limit of normal (ULN)
;
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
History of interstitial lung disease (ILD);
Patients >60 yr, with diabetes, or taking neurotoxic medications (↑ risk of peripheral neuropathy);
Rep:
Women of reproductive potential
;
Pedi: Safety and effectiveness not established in children.

Exercise Extreme Caution in:

Concurrent use of other hepatotoxic agents (↑ risk of hepatotoxicity).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), dry skin, eczema, pruritus, skin ulcers, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: pharyngitis, rhinitis, sinusitis

F and E: hypokalemia

GI: diarrhea, nausea, ↑liver enzymes, abdominal pain, anorexia, dyspepsia, gastroenteritis, HEPATOTOXICITY, mouth ulcers, vomiting

GU: urinary tract infection

Metab: weight loss

MS: arthralgia, back pain, joint disorder, leg cramps, synovitis, tenosynovitis

Neuro: headache, dizziness, paresthesia, peripheral neuropathy, weakness

Resp: bronchitis, cough, ILD, pneumonia

Misc: INFECTION (INCLUDING SEPSIS AND TUBERCULOSIS [TB] REACTIVATION)

Interactions ⬆ ⬇

Drug-drug:

Cholestyramine and activated charcoal cause a rapid and significant ↓ in levels of the active metabolite.
Methotrexate and other hepatotoxic drugs↑ risk of hepatotoxicity.
Rifampin↑ levels of the active metabolite.
May ↑ risk of bleeding with warfarin.
May ↓ response to and ↑ risk of adverse reactions from live vaccines; avoid live vaccinations and consider long half-life of leflunomide's active metabolite before administering once leflunomide discontinued.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg; 20 mg

Route/Dosage ⬆ ⬇

PO (Adults ): Loading dose: 100 mg once daily for 3 days; then initiate maintenance dose; Maintenance dose: 20 mg once daily (if intolerance occurs, may ↓ to 10 mg once daily).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits an enzyme required for pyrimidine synthesis; has antiproliferative and anti-inflammatory effects.

Therapeutic effects:

Decreased pain and inflammation, slowed structural progression, and improved physical function.

Classifications ⬆ ⬇

Therapeutic Classification: antirheumatics (DMARDs)

Pharmacologic Classification: immune response modifiers, pyrimidine synthesis inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 80% absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: 99%.

Metabolism/Excretion: Extensively metabolized in the liver to teriflunomide, which is responsible for pharmacologic activity; metabolites excreted in urine (43%) and feces (48%). Also undergoes biliary recycling.

Half-Life: 14–18 days.

Time/Action Profile ⬆ ⬇

(antirheumatic effect)

ROUTE	ONSET	PEAK	DURATION
PO	1 mo	3–6 mo	wk–mos‡

‡Due to persistence of active metabolite.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications. Aspirin, NSAIDs, or low-dose corticosteroids may be continued during therapy, but other agents for treatment of rheumatoid arthritis may require discontinuation.
Advise patient if a dose is missed to take as soon as remembered. Do not take two doses at the same time.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Discuss the possibility of hair loss with patient. Explore methods of coping.
Advise patient to notify health care provider if rash, mucous membrane lesions, unusual tiredness, abdominal pain, jaundice, or symptoms of ILD occur.
Instruct patient to avoid vaccinations with live vaccines during and following therapy without consulting health care provider.
Emphasize the importance of routine lab tests to monitor for side effects.
Rep:
May cause fetal harm. Advise women of reproductive potential to use effective contraception. If pregnancy is planned or suspected or if breastfeeding, notify health care provider immediately; an accelerated elimination procedure (see Implementation) must be used to ↓ levels more rapidly. Advise patient to avoid breastfeeding during therapy.

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Indications ⬇

Contraind./Precautions ⬆ ⬇