Arava 20 mg Tablets

Brand Name

Arava is the established brand name for this medication, widely regarded in the medical field for its role in managing specific autoimmune conditions. It has earned a reputation as a dependable option for clinicians addressing chronic inflammatory diseases.

International Nonproprietary Name (INN)

The active substance in this drug is identified by its International Nonproprietary Name (INN) as leflunomide. This synthetic isoxazol derivative is designed to deliver targeted immunosuppressive effects within the body.

Forms of Release

Arava is available exclusively in the form of film-coated tablets, offered in strengths of 10 mg, 20 mg, and 100 mg to accommodate varying therapeutic needs. These tablets are crafted for oral administration, providing a straightforward and consistent delivery method for patients requiring long-term treatment. Each dosage strength is tailored to support flexibility in managing the condition effectively.

Composition

The primary active ingredient in Arava is leflunomide, which drives its pharmacological activity. Alongside this core component, the tablets include several inactive substances to ensure stability, bioavailability, and ease of ingestion. These comprise lactose monohydrate, corn starch, and povidone as fillers and binders, with magnesium stearate acting as a lubricant. The film coating consists of hypromellose, titanium dioxide, and, in certain strengths, iron oxide yellow for color distinction. These auxiliary elements work together to maintain the drug’s integrity and enhance its administration profile.

Pharmacologic Properties

Pharmacodynamics

This medication exerts its therapeutic influence by modulating the immune system’s activity. Leflunomide functions primarily as an immunomodulatory agent, targeting the overactive immune responses characteristic of autoimmune disorders. It achieves this by inhibiting dihydroorotate dehydrogenase, a key enzyme in the de novo pyrimidine synthesis pathway, which is critical for the proliferation of activated lymphocytes, particularly T-cells. By restricting the availability of pyrimidines, it curtails the rapid division of these immune cells, thereby reducing inflammation and tissue damage in affected joints. Additionally, it exhibits mild anti-inflammatory properties, further alleviating symptoms in chronic conditions like rheumatoid arthritis, where immune-mediated destruction is a central feature.

Pharmacokinetics

The pharmacokinetic behavior of Arava outlines how leflunomide is processed in the body. Upon oral administration, it is rapidly absorbed from the gastrointestinal tract and converted in the gut wall and liver into its active metabolite, teriflunomide (A771726), which accounts for most of its clinical effects. Peak plasma concentrations of this metabolite are reached within 6 to 12 hours, though absorption can be slightly delayed by food without affecting total bioavailability, which exceeds 80%. Teriflunomide is highly bound to plasma proteins (over 99%), mainly albumin, and distributes into tissues with a volume of distribution of approximately 0.13 L/kg. It undergoes minimal further metabolism, with excretion occurring slowly via biliary (48%) and renal (43%) routes, resulting in an exceptionally long half-life of about 14 days due to enterohepatic recirculation. This prolonged presence necessitates specific management strategies in certain clinical scenarios.

Indications for Use

This medication is employed to treat disorders marked by excessive immune activity, harnessing its ability to temper inflammatory processes in specific autoimmune conditions.

Diseases and Conditions

Arava is indicated for the treatment of active rheumatoid arthritis in adults, aimed at reducing disease progression, alleviating joint inflammation, and improving physical function. It is also approved for active psoriatic arthritis, addressing both the joint and skin manifestations of this condition. By targeting the underlying immune dysregulation, it helps slow structural damage and enhance quality of life in these chronic illnesses, making it a pivotal option for patients requiring long-term disease control.

Contraindications

Despite its benefits, certain conditions render this medication inappropriate due to significant risks, necessitating careful screening before initiation.

Conditions Prohibiting Use

Arava is contraindicated in patients with known hypersensitivity to leflunomide, teriflunomide, or any tablet components, as reactions could range from mild rashes to severe allergic events. It is prohibited in individuals with severe hepatic impairment, given its metabolism and potential for hepatotoxicity. Patients with significant bone marrow suppression or severe infections (e.g., tuberculosis or HIV) should avoid it due to its immunosuppressive effects increasing infection risk. It is also barred in those with severe hypoproteinemia (e.g., nephrotic syndrome), as reduced protein binding could elevate free drug levels. Pregnant women, or those planning pregnancy without a confirmed negative test and contraception, must not use it due to teratogenic potential, ensuring safety across vulnerable groups.

Method of Administration and Dosage

How to Take

This medication is administered orally as tablets, swallowed whole with a sufficient quantity of water. It can be taken with or without food, as meals do not substantially alter absorption, though consistency in timing—preferably once daily—supports steady plasma levels. Patients should avoid crushing or chewing the tablets to preserve the intended release characteristics, ensuring optimal therapeutic delivery.

Dosages for Adults and Children

Dosing is tailored to the condition and patient profile, primarily for adults, as this drug is not indicated for pediatric use. For rheumatoid arthritis, treatment often begins with a loading dose of 100 mg daily for three days, followed by a maintenance dose of 10–20 mg daily, adjusted based on efficacy and tolerability. In psoriatic arthritis, the same regimen typically applies, with 20 mg daily as the standard maintenance dose after the initial loading phase. Arava’s dosing strategy aims to rapidly achieve therapeutic levels while minimizing early side effects, with long-term use guided by clinical response and monitoring.

Dose Adjustment in Specific Conditions

Adjustments are critical in renal or hepatic dysfunction. In mild to moderate renal impairment (creatinine clearance 30–80 mL/min), no specific reduction is required, but caution and monitoring are advised due to potential accumulation; severe cases (below 30 mL/min) lack sufficient data, often contraindicating use without specialist oversight. Hepatic impairment precludes use in severe cases, while mild to moderate dysfunction requires lower doses (e.g., 10 mg daily) with frequent liver function tests. Elderly patients may not need routine adjustment but warrant closer observation for toxicity due to age-related organ changes, ensuring a balanced approach to safety and efficacy.

Side Effects

This medication can elicit a variety of adverse reactions, ranging from mild to severe, and patients should be informed to facilitate prompt recognition and management.

Possible Adverse Reactions

Common effects include gastrointestinal disturbances like diarrhea, nausea, and abdominal pain, which may lessen with continued use. Elevated liver enzymes, indicating potential hepatotoxicity, occur frequently, with rare progression to severe liver injury. Skin reactions, such as rash or alopecia, affect some users, while hypertension may emerge, particularly early in therapy. Immunosuppression increases susceptibility to infections, from mild respiratory issues to opportunistic pathogens. Hematologic effects like leukopenia or anemia are less common but significant, and rare cases of interstitial lung disease or peripheral neuropathy have been reported. Regular monitoring mitigates these risks effectively.

Overdose

Symptoms of Overdose

Excessive intake of Arava can lead to pronounced symptoms requiring urgent attention. These include severe diarrhea, abdominal pain, and vomiting from gastrointestinal overload, alongside signs of liver stress such as jaundice or dark urine. Hematologic toxicity may manifest as unusual bleeding or fatigue, while neurological symptoms like dizziness or confusion could signal systemic effects. In extreme cases, respiratory distress or multi-organ failure may occur, particularly with massive doses or coexisting conditions, necessitating swift intervention.

First Aid Measures

In an overdose situation, immediate action is essential. If the patient is conscious and ingestion was recent, contact emergency services or poison control without inducing vomiting unless directed. Maintain airway and vital sign stability while awaiting help. In medical settings, activated charcoal is administered within an hour of ingestion to limit absorption, followed by supportive care—IV fluids, electrolyte correction, and monitoring. Cholestyramine or charcoal may be used to enhance elimination via enterohepatic interruption, with hemodialysis considered in severe renal compromise, though its utility is limited by high protein binding.

Drug Interactions

Effects on Other Medications

This medication can influence co-administered drugs due to its metabolic pathways. Leflunomide inhibits CYP2C9, potentially increasing levels of drugs like warfarin or phenytoin, heightening their effects or toxicity, requiring dose adjustments. It may also elevate NSAID concentrations, amplifying gastrointestinal risks. Conversely, rifampin or other CYP3A4 inducers can accelerate its metabolism, reducing efficacy. Cholestyramine or activated charcoal significantly lowers its levels by interrupting enterohepatic cycling, used intentionally in overdose but avoided otherwise. Monitoring and tailored adjustments ensure safe co-therapy.

Compatibility with Alcohol and Food

Alcohol should be strictly limited with Arava, as it exacerbates hepatotoxicity risk and may worsen gastrointestinal side effects, compromising safety. Food does not significantly impact absorption, allowing flexibility in timing with meals, though a consistent schedule aids predictability. No specific dietary restrictions apply, but patients should avoid excessive hepatotoxic substances to support liver health during therapy.

Special Precautions

Use During Pregnancy and Breastfeeding

This medication is contraindicated in pregnancy due to proven teratogenicity, including neural tube defects and craniofacial anomalies, classified as Category X. Women of childbearing potential must use reliable contraception and confirm negative pregnancy status before and during use, with a drug elimination procedure (cholestyramine washout) required before conception. Leflunomide enters breast milk in small amounts; breastfeeding is not recommended due to potential infant immunosuppression, with alternatives preferred.

Impact on Driving and Operating Machinery

Arava may impair alertness or coordination due to dizziness or fatigue, particularly during initiation or dose changes. Patients should refrain from driving or operating machinery until they assess its effects, prioritizing safety in daily activities.

Considerations for Elderly and Pediatric Patients

In elderly patients, this drug requires cautious use due to increased hepatotoxicity and infection risks, often starting at 10 mg daily with close liver and immune monitoring. It is not approved for children under 18, as safety and efficacy data are lacking, with alternative therapies preferred for juvenile arthritis. Adult dosing adjustments ensure tolerability across age groups.