Teriflunomide: Clinical Profile, Mechanism of Action and Dosage
Teriflunomide is an oral immunomodulatory agent with anti-inflammatory properties designed for the pathogenetic treatment of multiple sclerosis. The drug is the active metabolite of leflunomide and belongs to the class of selective enzyme inhibitors.
The mechanism of action of teriflunomide is based on the specific and reversible inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This enzyme plays a key role in the de novo synthesis of pyrimidine. Since rapidly dividing lymphocytes (T and B cells) critically depend on this synthesis pathway for their proliferation, teriflunomide effectively limits the multiplication of auto-aggressive lymphocytes responsible for damaging the myelin sheath of nerve fibers in multiple sclerosis.
An important feature of the drug is its cytostatic effect primarily on activated lymphocytes, while resting cells maintain their viability through alternative pyrimidine synthesis pathways. This ensures a pronounced therapeutic effect while maintaining a certain level of the body's immune response.
Indications
Teriflunomide is used as monotherapy to modify the course of the disease in adult patients:
- Relapsing-Remitting Multiple Sclerosis (RRMS): to reduce the frequency of clinical relapses and slow the progression of physical disability.
- Clinically Isolated Syndrome (CIS): the first manifestation of a demyelinating disease, indicating a high risk of conversion to clinically definite multiple sclerosis.
- The drug is effective in reducing the number and volume of active inflammatory brain lesions detected by Magnetic Resonance Imaging (MRI).
Dosage and administration
Teriflunomide therapy should be conducted under the supervision of a neurologist specializing in the treatment of multiple sclerosis. The drug is available as film-coated tablets in 7 mg and 14 mg strengths.
- Standard Regimen: The recommended therapeutic dose is 14 mg once daily.
- Administration Rules: The tablet should be taken whole, without chewing or crushing, regardless of food intake. Consistent dosing time helps maintain a stable plasma concentration of the active substance.
- Safety Monitoring: Before starting treatment, levels of ALT, AST, total bilirubin, a complete blood count, and a tuberculosis test must be performed. During the first 6 months of therapy, liver enzyme monitoring should be conducted every 2 weeks, then every 2 months thereafter.
- Accelerated Elimination Procedure: Due to its long half-life (10 to 19 days), teriflunomide can remain in the body for up to 2 years after discontinuation. If urgent removal is required (e.g., when planning pregnancy or in case of intoxication), cholestyramine or activated charcoal is used according to a special 11-day regimen.
The use of teriflunomide is strictly limited in the presence of the following factors:
- Severe Hepatic Impairment (Child-Pugh Class C), as the drug undergoes intensive metabolism in the liver.
- Pregnancy and Lactation: The drug has significant teratogenic potential. Women of childbearing age must use reliable methods of contraception. Therapy must be stopped immediately if pregnancy is suspected.
- Severe Immunodeficiency States (e.g., AIDS) or significant bone marrow suppression (anemia, leukopenia, thrombocytopenia).
- Severe Active Infections: until the patient has fully recovered.
- Severe Renal Impairment requiring dialysis (clinical experience is limited).
- Hypoproteinemia: severe forms of reduced blood protein levels (as the drug is 99% bound to albumin).
Therapy requires vigilance regarding the following possible reactions:
- Hepatotoxicity: increased levels of liver transaminases (ALT). Severe liver damage may occur in rare cases.
- Dermatologic Reactions: temporary hair thinning (alopecia) is common and usually resolves on its own without discontinuing the drug. Rash and paresthesia are also possible.
- Gastrointestinal Tract: diarrhea (most common at the start of treatment), nausea, and upper abdominal pain.
- Cardiovascular System: potential increase in blood pressure (regular BP monitoring is required).
- Infections: increased susceptibility to upper respiratory tract infections, and reactivation of latent tuberculosis.
- Neurology: peripheral neuropathy (tingling, numbness of extremities).
