Nodia10 mg

Established Indications

• Rheumatoid Arthritis (RA): Nodia is approved for the treatment of active rheumatoid arthritis in adults, to reduce signs and symptoms and to slow the progression of structural joint damage. It may be used as monotherapy or in combination with methotrexate in patients who have had an inadequate response to methotrexate alone.

Guideline-Supported / Off-Label Uses

• Psoriatic Arthritis: Nodia is used off-label, with support from rheumatology guidelines, for active psoriatic arthritis in patients who cannot tolerate or have not responded to other DMARDs.
• Other inflammatory arthropathies: Occasionally used off-label at a specialist's discretion when standard DMARDs are unsuitable.

Nodia is not established as effective in children (see Pediatric Use) and should be prescribed only by, or in consultation with, a physician experienced in disease-modifying antirheumatic drugs.

Each film-coated tablet contains Leflunomide INN as the active pharmaceutical ingredient, commonly available in strengths of 10 mg and 20 mg, together with standard pharmaceutically approved excipients.

Nodia is a synthetic isoxazole-derivative disease-modifying antirheumatic drug (DMARD) with immunomodulatory and anti-inflammatory properties. It is a prodrug that is rapidly and almost completely converted, in the gut wall and liver, to its active metabolite, teriflunomide, which is responsible for essentially all of its therapeutic activity. Nodia is used to modify the underlying disease process of active rheumatoid arthritis rather than simply provide symptomatic relief.

Nodia belongs to the class of Disease-Modifying Antirheumatic Drugs (DMARDs), specifically categorized as a pyrimidine synthesis inhibitor (isoxazole immunomodulatory agent).

Mechanism of Action

Leflunomide's active metabolite, teriflunomide, inhibits dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme in the de novo pyrimidine synthesis pathway. This blocks the proliferation of activated (but not resting) lymphocytes, which rely heavily on de novo pyrimidine synthesis during rapid clonal expansion, thereby dampening the autoimmune and inflammatory response that drives joint damage in rheumatoid arthritis.

Pharmacokinetics

Nodia tablets should be swallowed whole with water and may be taken with or without food, at approximately the same time each day. Tablets should not be crushed or split unless specifically directed by a physician. Baseline and periodic laboratory monitoring (liver function tests, complete blood count, blood pressure) are required throughout treatment - see Precautions and Warnings.

Clinically Significant Interactions

• Hepatotoxic drugs (e.g., methotrexate): Concomitant use with Nodia increases the risk of hepatotoxicity; avoid where possible and monitor liver enzymes closely if combined.
• Warfarin: Nodia's active metabolite may decrease peak INR by approximately 25%; monitor INR closely, especially when starting or stopping Nodia.
• CYP2C8 substrates (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone): Nodia increases exposure to these drugs; dose reduction of the substrate may be needed.
• Rosuvastatin and other BCRP/OATP1B1/1B3 substrates: Exposure is increased by Nodia; rosuvastatin dose should generally not exceed 10 mg daily during concurrent use.
• Oral contraceptives: Nodia may increase exposure to ethinylestradiol/levonorgestrel; inform your physician if using hormonal contraception.
• CYP1A2 substrates: Exposure to these drugs may decrease with concomitant Nodia use.
• OAT3 substrate drugs: Exposure may increase with Nodia; monitor for toxicity.
• Live vaccines: Should be avoided during treatment with Nodia due to immunosuppression.
• Other immunosuppressants/DMARDs: Combination with Nodia may increase risk of infection and hematologic toxicity; use only under close specialist supervision.

Common Side Effects

• Diarrhea, nausea, abdominal pain, dyspepsia
• Headache, dizziness
• Reversible alopecia (hair thinning)
• Rash, mild allergic reactions
• Elevated liver enzymes
• Mild hypertension
• Upper respiratory tract infections

Serious Side Effects (Seek Medical Attention)

Pregnancy

Nodia is contraindicated in pregnancy. It is teratogenic and embryotoxic in animal studies, and its active metabolite persists in plasma for a prolonged period due to enterohepatic recirculation. Pregnancy must be excluded before starting Nodia, and effective contraception must be used during treatment and continued afterward as advised by a physician. If pregnancy occurs during treatment with Nodia, stop the medicine immediately and contact your physician urgently; an accelerated drug elimination procedure (using cholestyramine or activated charcoal, under direct medical supervision) may be required.

Male Patients Planning Fatherhood

Available data suggest limited risk, but as a precaution some guidelines recommend confirming low plasma levels before conception; discuss Nodia use with a physician if planning a pregnancy.

Lactation

Nodia and its active metabolite pass into breast milk in animal studies; breastfeeding is not recommended during treatment with Nodia because of the potential for serious adverse reactions in the nursing infant. Use only if clearly needed and only after consulting a physician.

Boxed Warnings

Hepatotoxicity: Severe and sometimes fatal liver injury has been reported with Nodia. Baseline liver function tests are required before starting, with monthly monitoring for the first six months and periodic monitoring thereafter. Avoid Nodia in patients with pre-existing liver disease or elevated baseline liver enzymes, and avoid or minimize alcohol and other hepatotoxic medications.

Embryo-Fetal Toxicity: See Pregnancy and Lactation.

Other Precautions

• Tuberculosis and Infections: Screen for active and latent tuberculosis before starting Nodia, as it is immunosuppressive and may reactivate latent TB or predispose to serious infections, including opportunistic infections.
• Live vaccines: Should be avoided during treatment with Nodia.
• Bone marrow suppression: Monitor complete blood counts periodically; risk increases with concurrent methotrexate or other myelosuppressive drugs.
• Blood pressure: Nodia may cause or worsen hypertension; monitor blood pressure regularly.
• Skin reactions: Rarely, severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS have occurred; discontinue Nodia immediately if suspected.
• Peripheral neuropathy: May occur, particularly in patients with risk factors; consider discontinuing Nodia if it develops.
• Interstitial lung disease: Rare but potentially fatal; evaluate promptly if new or worsening respiratory symptoms occur.
• Skin ulcers: Reported with concomitant use of Nodia and methotrexate.

Reported overdose experience with Nodia is limited but generally consistent with its known side-effect profile, including diarrhea, abdominal pain, leukopenia, anemia, and elevated liver enzymes. There is no specific antidote. In case of suspected overdose of Nodia, seek immediate medical attention or contact emergency services / a poison control center. Cholestyramine or activated charcoal may be used under medical supervision to accelerate elimination of the active metabolite; it is not removed by hemodialysis or peritoneal dialysis. Do not attempt home treatment for a suspected overdose.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal Impairment

Limited data are available; use Nodia with caution and close monitoring in patients with renal impairment.

Hepatic Impairment

Nodia is contraindicated in severe hepatic impairment. Use with caution and enhanced monitoring in mild-to-moderate impairment (see Contraindications and Precautions).

Elderly

No specific dose adjustment of Nodia is required based on age alone, but elderly patients should be monitored closely given a higher likelihood of comorbidities and concomitant medications.

Pediatric Patients

See Pediatric Use.

Women of Childbearing Potential

See Pregnancy and Lactation for contraception requirements before and during Nodia treatment.

Duration of treatment with Nodia is individualized by the treating physician based on clinical response, tolerability, and laboratory monitoring results. As a disease-modifying agent for a chronic condition, Nodia is often continued long-term (months to years) provided the benefit continues to outweigh risks and monitoring remains satisfactory; do not stop or change the dose of Nodia without medical advice.

Disease-Modifying Antirheumatic Drugs (DMARDs); Immunomodulatory/Immunosuppressive agents; Pyrimidine synthesis inhibitors (isoxazole derivatives) - the class to which Leflunomide belongs.

Leflunomide is rapidly converted to its active metabolite, teriflunomide, which inhibits dihydroorotate dehydrogenase (DHODH), a rate-limiting mitochondrial enzyme in de novo pyrimidine synthesis. By restricting pyrimidine availability, teriflunomide arrests the proliferation of activated lymphocytes in the G1 phase of the cell cycle, reducing the autoimmune-driven inflammatory cascade responsible for joint damage in rheumatoid arthritis.

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The safety and effectiveness of Nodia have not been established in pediatric patients. In clinical trials conducted in children with polyarticular juvenile idiopathic arthritis, Nodia did not demonstrate effectiveness. Nodia is therefore not recommended for use in children and adolescents outside of exceptional circumstances guided by a specialist.