Teriflunomide

Conditions Treated

Teriflunomide is used to treat adults with various relapsing forms of multiple sclerosis (MS). These include:

• Clinically isolated syndrome: This refers to a first episode of neurologic symptoms that lasts at least 24 hours and may be the first sign of MS.
• Relapsing-remitting disease: This is a form of MS characterized by clearly defined attacks of new or increasing neurologic symptoms, followed by periods of partial or complete recovery.
• Active secondary progressive disease: This occurs when the disease begins to worsen more steadily over time, but the patient still experiences occasional relapses.

Purpose of Treatment

Teriflunomide is not a cure for multiple sclerosis. Instead, it is used as a long-term management strategy to help control the disease. The medication is typically prescribed to:

• Decrease the number of clinical relapses or flare-ups.
• Slow down the accumulation of physical problems and disability that can occur as MS progresses.

Mechanism of Action

Teriflunomide is used to treat relapsing forms of multiple sclerosis (MS). It belongs to a class of drugs known as immunomodulatory agents. In MS, the body's immune system attacks the central nervous system, specifically damaging the myelin sheath that protects nerve fibers.

The medication works by blocking an enzyme called dihydroorotate dehydrogenase. This enzyme is necessary for the production of pyrimidine, a building block for DNA. Certain white blood cells, specifically T and B lymphocytes, require this enzyme to multiply rapidly when they are activated.

Impact on Multiple Sclerosis

By inhibiting this enzyme, teriflunomide limits the growth and spread of these overactive immune cells. This leads to several key effects in the body:

• Reduced Inflammation: Lowering the number of active lymphocytes reduces the inflammatory response that attacks the brain and spinal cord.
• Nerve Protection: By decreasing inflammation, the drug helps prevent damage to the myelin sheath and the underlying nerve fibers.
• Symptom Management: These actions help reduce the frequency of MS flare-ups (relapses) and may help slow down the progression of physical disability.

While teriflunomide helps control the activity of MS, it does not cure the disease or repair damage that has already occurred.

Common Side Effects

Many people taking teriflunomide experience mild side effects. These may include:

• Hair thinning or hair loss
• Diarrhea
• Nausea
• Headache
• Joint pain
• Cold symptoms, such as a runny nose or cough
• Abnormal results on liver function tests

Serious Side Effects

While less common, some side effects require immediate medical attention. Contact your doctor right away if you notice:

• Liver problems: Symptoms include yellowing of the skin or eyes (jaundice), dark urine, or pain in the upper right side of the stomach.
• Infections: Signs such as fever, chills, or persistent sore throat, as the medication can lower your ability to fight germs.
• Lung issues: New or worsening shortness of breath or a dry cough.
• Nerve damage: Numbness, tingling, or burning sensations in the hands or feet (peripheral neuropathy).
• Severe skin reactions: A skin rash, peeling, or sores in the mouth or eyes.
• High blood pressure: New or worsening hypertension.

Boxed Warnings

Hepatotoxicity: There is a risk of severe, life-threatening liver injury. Liver enzyme levels must be checked before starting the medication and monitored at least monthly for the first six months of treatment.

Teratogenicity: This medication can cause major birth defects or pregnancy loss. It is not for use by pregnant women or those who may become pregnant and are not using effective birth control.

Pregnancy and Elimination

Teriflunomide can stay in the blood for up to two years after the last dose. If pregnancy is desired or if serious side effects occur, an accelerated elimination procedure using cholestyramine or activated charcoal may be used to clear the drug from the system more quickly. Men taking teriflunomide who wish to father a child should also discuss elimination procedures with their healthcare provider.

Infections and Immune System

The medication can lower white blood cell counts and increase the risk of serious infections. Screening for tuberculosis is required before starting therapy. Live vaccines should be avoided during treatment and for at least six months after stopping.

Additional Monitoring

• Blood Pressure: Blood pressure may increase during treatment and requires regular checks.
• Nerve Damage: Peripheral neuropathy, characterized by numbness or tingling in the extremities, has been reported.
• Lung Problems: Interstitial lung disease is a rare but serious risk; new or worsening respiratory symptoms require medical evaluation.
• Skin Reactions: Severe skin conditions, such as Stevens-Johnson syndrome, may occur and require immediate discontinuation of the drug.

Pregnancy Considerations

Teriflunomide carries a high risk of causing severe birth defects or the death of an unborn baby. It must not be taken by individuals who are pregnant or who may become pregnant during treatment. A pregnancy test is required before starting the medication to confirm that the patient is not pregnant.

This medication remains in the body for a significant amount of time after treatment ends. Without a medical procedure to speed up its removal, it can take up to two years for the drug levels to drop low enough to be considered safe for pregnancy. If a patient becomes pregnant while taking teriflunomide or within two years after stopping it, they should contact a healthcare provider immediately.

Contraception and Prevention

• For women: Effective birth control must be used throughout the duration of treatment and during the waiting period after treatment stops.
• For men: Men taking teriflunomide whose partners are able to become pregnant should use effective contraception to avoid pregnancy during treatment and for the required period afterward.

Breastfeeding

It is not known if teriflunomide passes into breast milk or how it might affect a nursing infant. Due to the risk of serious side effects, breastfeeding is typically not recommended while using this medication. Patients should consult with their healthcare team to weigh the risks and benefits of breastfeeding versus alternative feeding methods.

Dosage Forms

Teriflunomide is available in the following form:

• Oral Tablet: This is a film-coated tablet taken by mouth.

The medication is typically taken daily and can be taken with or without food.

FDA Approval and Indications

Teriflunomide is approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS) in adults. The approved indications include:

• Clinically isolated syndrome
• Relapsing-remitting disease
• Active secondary progressive disease

Boxed Warnings

The FDA has assigned a boxed warning to teriflunomide, which is the most serious level of warning for prescription medications. These warnings cover two primary areas of concern:

• Hepatotoxicity: There is a risk of severe, potentially fatal liver injury. Healthcare providers are required to conduct liver function tests before starting treatment and continue monitoring liver enzymes monthly for at least the first six months of therapy.
• Teratogenicity: Teriflunomide may cause serious birth defects or fetal death. It is contraindicated in pregnant women and in women of childbearing potential who are not using effective contraception. Because the drug can remain in the body for a long period after the last dose, a specific drug elimination procedure is often required for patients who wish to become pregnant or father a child.

Safety Requirements and Monitoring

In addition to liver monitoring, regulatory guidelines require that patients be screened for latent tuberculosis (TB) before beginning treatment. Blood pressure should also be checked at the start of therapy and monitored periodically thereafter, as the medication can cause hypertension.

Long-Term Presence in the Body

After you stop taking teriflunomide, the medication can remain in your system for a long time. Without intervention, it may take anywhere from 8 months to 2 years for the drug to naturally clear from your body. Because of this long half-life, you must continue to use effective birth control until blood tests confirm the drug is no longer at a level that could harm a developing fetus.

Accelerated Elimination Procedure

If you need to clear the drug from your system quickly—such as when planning a pregnancy or if you experience a serious side effect—your doctor may prescribe an accelerated elimination procedure. This process helps the body get rid of the medication in days rather than months.

The elimination process typically involves:

• Taking specific medications, such as cholestyramine or activated charcoal powder, for 11 days.
• The 11 days of treatment do not need to be consecutive unless your doctor specifies otherwise.
• Undergoing blood tests after the procedure to verify that the levels of teriflunomide in your system are low enough.
• Repeating the treatment if blood levels remain above the target threshold.

Do not stop taking teriflunomide without consulting your healthcare provider. They will determine if an elimination procedure is necessary based on your reason for stopping the medication.