Leflunomide

Leflunomide Tablets, USP are indicated for the treatment of adults with active rheumatoid arthritis (RA). Leflunomide tablets are a pyrimidine synthesis inhibitor indicated for the treatment of adults with active rheumatoid arthritis. ( 1 )

• Loading dosage for patients at low risk for leflunomide -associated hepatotoxicity and leflunomide -associated myelosuppression: 100 mg daily for 3 days
• Maintenance dosage: 20 mg daily
• Maximum recommended daily dosage: 20 mg once daily
• If 20 mg once daily is not tolerated, may decrease dosage to 10 mg once daily
• Screen patients for active and latent tuberculosis, pregnancy test (females), blood pressure, and laboratory tests before starting leflunomide tablets
• Recommended Dosage The recommended dosage of Leflunomide is 20 mg once daily
• Treatment may be initiated with or without a loading dose, depending upon the patient's risk of leflunomide -associated hepatotoxicity and leflunomide associated myelosuppression
• The loading dosage provides steady-state concentrations more rapidly
• For patients who are at low risk for leflunomide-associated hepatotoxicity and leflunomide-associated myelosuppression the recommended leflunomide loading dosage is 100 mg once daily for 3 days
• Subsequently administer 20 mg once daily
• For patients at high risk for leflunomide-associated hepatotoxicity (e.g., those taking concomitant methotrexate) or leflunomide-associated myelosuppression (e.g., patients taking concomitant immunosuppressants), the recommended leflunomide dosage is 20 mg once daily without a loading dose [see Warnings and Precautions ]
• The maximum recommended daily dosage is 20 mg once per day. …

Leflunomide Tablets, USP are available in two strengths: Tablets: 10 mg, supplied as white, round bi-convex tablets debossed with "HP 43" on one side and plain on the other. Tablets: 20 mg, supplied as white, triangular bi-convex tablets debossed with "HP 44" on one side and plain on the other. Tablets: 10 mg, 20 mg ( 3 )

• The safety and effectiveness of leflunomide
• In pediatric patients have not been established
• The safety and effectiveness of leflunomide in the treatment of polyarticular course juvenile idiopathic arthritis (JIA) was evaluated in a single multicenter, double-blind, active-controlled trial in 94
• Pediatric patients (1:1 randomization) with polyarticular course juvenile idiopathic arthritis (JIA) as defined by the American College of Rheumatology (ACR)
• In this population, leflunomide treatment was found not to be effective. …

Of the total number of subjects in controlled clinical trials (Trials 1, 2, and 3) of leflunomide, 234 subjects were 65 years and over [see Clinical Studies (14) ]. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals c …

• Embryo-Fetal Toxicity Advise females of reproductive potential Of the potential for fetal harm if leflunomide is taken during pregnancy
• To notify their healthcare provider immediately if a pregnancy occurs or is suspected
• To use effective contraception during treatment with leflunomide and until the active metabolite (teriflunomide) plasma concentration is verified to be less than 0.02 mg/L [see Warnings and Precautions , Use in Specific Populations , Clinical Pharmacology ]. …

• Leflunomide tablets are contraindicated in: Pregnant women
• Leflunomide may cause fetal harm
• If a woman becomes pregnant while taking this drug, stop leflunomide, apprise the patient of the potential hazard to the fetus, and begin a drug elimination procedure [see Warnings and Precautions ( 5.1 and 5.3 ) and Use in Specific Populations ]
• Patients with severe hepatic impairment [see Warnings and Precautions ]. …

Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Drug interaction studies have been conducted with both leflunomide and with its active metabolite, teriflunomide, where the metabolite was directly administered to the test subjects. Effect of potent CYP and transporter inducers Leflunomide is metabolized by CYP450 metabolizing enzymes. Concomitant use of leflunomide and rifampin, a potent inducer of CYP and transporters, increased the plasma concentration of teriflunomide by 40%. …

After stopping leflunomide, it is recommended that an accelerated drug elimination procedure be used to reduce the plasma concentrations of the active metabolite, teriflunomide. ( 5.3 ) Severe infections (including sepsis), pancytopenia, agranulocytosis and thrombocytopenia: Stop leflunomide and use accelerated elimination procedure. Do not start leflunomide in patients with active infection. Monitor CBCs during treatment with leflunomide. ( 5.4 ) Stevens-Johnson syndrome and toxic epidermal necrolysis: Stop leflunomide and use accelerated elimination procedure. …

The following serious adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ] Immunosuppression [see Warnings and Precautions (5.4) ] Bone marrow suppression [see Warnings and Precautions (5.4) ] Stevens-Johnson syndrome and toxic epidermal necrolysis [see Warnings and Precautions (5.5) ] Peripheral neuropathy [see Warnings and Precautions (5.7) ] Interstitial lung disease [see Warnings and Precautions (5.8) ] The most commonly reported adverse reactions (≥10%) regardless of relation to leflunomide treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, dyspepsia. …

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to leflunomide during pregnancy. Health care providers and patients are encouraged to report pregnancies by calling 1-877-311-8972 or visit http://www.pregnancystudies.org/participate-in a-study/. Risk Summary Leflunomide is contraindicated for use in pregnant women because of the potential for fetal harm. …

There have been reports of chronic overdose in patients taking leflunomide at daily dose up to five times the recommended daily dose and reports of acute overdose in adults and children. Adverse events were consistent with the safety profile for leflunomide [See Adverse Reactions (6) ]. The most frequent adverse events observed were diarrhea, abdominal pain, leukopenia, anemia and elevated liver function tests. In the event of a significant overdose or toxicity, perform an accelerated drug elimination procedure to accelerate elimination [see Warnings and Precautions (5.3) ]. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.