Teriflunomide: Uses and Side Effects

Drug Overview

Teriflunomide is a drug that has both anti-inflammatory and immunomodulatory properties. It acts by inhibiting pyrimidine synthesis. It is mostly used to manage the relapsing type of multiple sclerosis. The Food and Drug Administration (FDA) has approved Teriflunomide for the management of multiple sclerosis, but with warnings of hepatotoxicity and teratogenicity. Read the article in detail to know more about the usage, side effects, warnings, dosage, and mechanism of action of Teriflunomide.

How Does the Drug Teriflunomide Work?

The exact mechanism of action of Teriflunomide is not yet known. However, the proposed mechanism of action of the drug is that it inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, thereby inhibiting pyrimidine synthesis and reducing the number of lymphocytes in the central nervous system. Much research still needs to be done to understand the exact mechanism of Teriflunomide in managing multiple sclerosis.

Uses

Teriflunomide is a drug used to manage different variants of multiple sclerosis (a neuromuscular disease), such as:

• Remitting form of multiple sclerosis.

• Relapsing form of multiple sclerosis.

• Secondary and progressive variants of multiple sclerosis.

• Clinically isolated variants of multiple sclerosis.

Doses

• Teriflunomide is available as oral tablets in two dosages: 7 mg and 14 mg.

• It has to be taken orally with water. It can be consumed with or without food, as prescribed by the doctor.

Warnings

• Risk of Teratogenicity: Teriflunomide use carries a teratogenic risk, so it should be avoided in pregnant and lactating women.

• Risk of Hepatotoxicity: Teriflunomide should be avoided in patients with hepatic impairment as it carries the risk of liver failure and death. It is advised to inform the doctor promptly if any symptoms occur, such as dark urine, abdominal pain, or jaundice (yellowish discoloration of the skin and eyes).

• Risk of Immunosuppression: Teriflunomide decreases overall white blood cell counts and may cause bone marrow suppression.

For Patients

What Is Multiple Sclerosis?

It is an autoimmune condition (when the body's defense mechanism attacks its own cells) that affects the central nervous system (brain and spinal cord), resulting in demyelination of nerve fibers. The associated signs and symptoms of multiple sclerosis are vision impairment, tingling and numbness in the limbs, loss of memory, and urinary problems.

Stages of Multiple Sclerosis

There are three stages of multiple sclerosis:

• Relapsing stage.

• Primary progressive stage.

• Secondary progressive stage.

Know More About Teriflunomide Medication:

When and Why to Take Teriflunomide?

• Teriflunomide is a drug prescribed to adults with different variants of multiple sclerosis after a thorough examination of the patient's condition by the doctor.

• Teriflunomide is prescribed to patients with multiple sclerosis to minimize the underlying symptoms by decreasing the swelling and immune cell activity that can cause damage to the nerves.

Effectiveness of Teriflunomide Against Multiple Sclerosis:

Teriflunomide is quite effective in reducing the symptoms associated with multiple sclerosis cases, like tingling and numbness in the limbs, memory loss, and bowel dysfunction.

Things to Inform The Doctor Before They Prescribe Teriflunomide Medication:

• Before starting the drug Teriflunomide, inform the doctor of any liver disease, as the drug has a toxic effect on the liver.

• Inform the doctor if pregnant or planning to become pregnant, as the drug carries the risk of teratogenicity.

• Tell the doctor if you have any allergies to any drugs or compositions.

• Breastfeeding mothers should inform their doctor before starting the Teriflunomide drug, as it carries the risk of teratogenicity

• Inform the doctor of any underlying diseases like tuberculosis, recent lung infections, or a history of any lung disease.

• Inform the doctor if any live vaccine was administered within the past 6 months.

• Inform the doctor of any history of blood or immune system disorders.

Starting Teriflunomide Medication

How To Take Teriflunomide?

• Teriflunomide is available as an oral tablet in 7 mg and 14 mg strengths.

• The drug can be taken with or without food once daily in the dosage prescribed by the doctor based on the patient's condition.

• It is advised to take the tablet whole with water, and not to crush or chew it.

Things to Do After One Starts Taking Teriflunomide

Look Out for the Side Effects

Common side effects associated with Teriflunomide are:

• Loss of hair.

• The blurring of vision.

• Toothache.

• Pain in the joints and muscles.

• Weight loss.

• Acne.

• Stomach upset.

• Nausea and vomiting.

• Stuffy nose.

• Shivering.

• Depression.

Serious side effects associated with Teriflunomide are

• Headache.

• Dizziness.

• Confusion.

• Pale skin.

• Fever, cough, and chills.

• Sore throat.

• Numbness and burning sensation in the hands and feet.

• Loss of muscular coordination and tone.

• Difficulty in swallowing.

• Rashes and peeling of the skin.

• Shortness of breath.

• Cold and gray skin.

• Swelling of the lips, face, and mouth.

• Chest tightness.

There are various other side effects of Teriflunomide. It is advised to inform the doctor immediately in case any side effects are observed.

Dietary Alterations: No dietary alterations are needed when on Teriflunomide. Teriflunomide can be taken with or without food.

What Should Be Done if the Dose Is Missed?

If a dose is missed or forgotten, take it as soon as it is remembered. Avoid taking a double dose to make up for a missed dose.

What Should Be Done in Case of Overdose of Teriflunomide?

In case of an overdose of Teriflunomide, inform the doctor as soon as possible and call the poison control center. In case of severe side effects like breathlessness and seizures, call the emergency services quickly and inform the poison control center.

When to Call Your Doctor?

Get help right away if you notice:

• Signs of an allergy, like swelling, hives, or trouble breathing.

• Swelling in the face, lips, or throat (angioedema).

• Serious skin problems, like purple spots, rashes, or blisters.

• New or worse breathing problems.

• If you become pregnant while taking the medicine.

• Pain on the right side of your stomach, dark pee, or yellow skin or eyes, these can be signs of liver issues.

• Fever or chills.

• Numbness, tingling, or other nerve problems.

• High blood pressure.

• Easy bruising or bleeding that’s not normal.

What Should Be Avoided When on Teriflunomide Medication?

• Avoid close contact with persons with cold, flu, or upper respiratory tract infections, as it may worsen the infections.

• Avoid receiving any live vaccine while on Teriflunomide and for 6 months after stopping the drug.

• Avoid contact with individuals who have received live vaccines recently.

• Avoid sports activities that increase the risk of cuts, bruises, and other injuries, as they can worsen the condition.

Storage of Teriflunomide:

• Teriflunomide tablets are stored at room temperature, around 20 to 25 degrees Celsius.

• The drug Teriflunomide should be kept away from heat, light, and moisture.

• Discard the drugs that are expired.

• Avoid discarding or flushing the medication down the drain.

• Keep the drug away from the children and pets.

Avoid Self-Prescription: Teriflunomide should be taken only when prescribed by a doctor and based on the clinical condition. The drug should be consumed in the exact dosage and schedule as prescribed by the doctor to minimize or reduce the adverse effects.

Staying On Teriflunomide:

• Teriflunomide should be taken at the exact dosage and schedule as prescribed by the doctor.

• Inform the doctor immediately if any dose is missed.

• Check for improvement in the health status and symptoms. Inform the doctor about it in the follow-up visits.

• In case of worsening symptoms and health status, inform the doctor immediately.

For Doctors

Indications: Teriflunomide is indicated in patients with remitting, relapsing, and secondary progressive multiple sclerosis.

Pharmacology:

• Mechanism of Action: Teriflunomide, an immunomodulatory agent, acts by restricting the synthesis of pyrimidine. The exact mechanism, however, is yet to be known. Teriflunomide inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, thereby reducing pyrimidine synthesis and decreasing the formation of activated lymphocytes in the central nervous system, thereby showing anti-inflammatory effects.

• Pharmacodynamics: Teriflunomide is an immunomodulatory and anti-inflammatory agent that acts by inhibiting the formation of pyrimidine nucleotides, thereby reducing the volume of activated lymphocytes in the central nervous system.

Ingredients:

Active Ingredient: The only active ingredient is Teriflunomide.

Inactive Ingredients: The inactive ingredients are:

• Starch.

• Silicon dioxide.

• Lactose monohydrate.

• Magnesium stearate.

• Microcrystalline cellulose.

• Polyethylene glycol.

• Titanium dioxide.

• Ferric oxide yellow.

• Talc.

Absorption: The peak plasma concentration is reached after a single dose of oral Teriflunomide within one to four hours.

Distribution: The volume of distribution is approximately 11 liters after a single intravenous dose of Teriflunomide.

Metabolism: Teriflunomide is primarily metabolized by hydrolysis. Other secondary pathways are oxidation and sulfate conjugation.

Elimination: Teriflunomide is primarily eliminated via the bile. Thirty-seven percent of the drug is eliminated from feces and 26 percent from urine.

Protein Binding: Almost 99 percent of the drug Teriflunomide is extensively bound to plasma proteins.

Total Body Clearance: The drug Teriflunomide has an average clearance of 30 mL/h.

Toxicity:

• Teriflunomide shows toxic effects in pregnant and lactating mothers as it carries the risk of teratogenicity. So, it should be strictly avoided in pregnant and lactating mothers.

• The drug also carries the risk of hepatotoxicity and liver failure, so it should be strictly avoided in patients with liver impairment.

Half-Life: The estimated half-life of the drug is around 18 to 20 days.

Warning and Precautions:

• Teriflunomide should be avoided in pregnant and lactating women as it has a risk of teratogenicity, according to the studies.

• Teriflunomide should be avoided in patients with liver impairment as it is toxic to the liver and can result in liver failure or death due to toxicity.

• Teriflunomide should be avoided in patients with bone marrow disease, lung infections, and other serious infections. The drug can only be started in such patients after treating the underlying infection.

Doses and Forms:

The drug Teriflunomide is available as an oral tablet in 7 mg and 14 mg doses.

Administration of the Drug:

• The drug Teriflunomide is prescribed orally, one tablet daily with water in the dosage recommended by the doctor after a thorough examination and monitoring of the patient's clinical condition.

• The patient's ALT (alanine aminotransferase) and bilirubin levels are monitored for six months after starting the drug.

• For children, the doctor determines the drug dosage based on the patient's symptoms.

• All lab tests, such as complete blood count (CBC), liver function tests, and kidney function tests, should be performed by the doctor before starting Teriflunomide.

Contraindications:

• The drug Teriflunomide is contraindicated in patients with liver impairment as it is toxic to the liver and can result in liver failure.

• The drug Teriflunomide is contraindicated in pregnant and lactating mothers due to its teratogenic potential.

• The drug Teriflunomide is contraindicated in patients with underlying severe infection or bone marrow disease, as it may cause immunosuppression. It should only be started after the underlying infections are under control.

Drug Interactions:

• Adenovirus 7 live vaccine, when combined with Teriflunomide, increases the risk of severe infections.

• There is an increased risk of adverse side effects if the drug Teriflunomide is combined with Abatacept and Adalimumab.

• Teriflunomide, when combined with Acetaminophen, reduces Acetaminophen's serum concentration.

• Teriflunomide, when combined with Acyclovir, reduces Acyclovir's serum concentration.

• When combined with activated charcoal, the serum concentration of Teriflunomide decreases.

Vaccines:

• Live attenuated vaccines are made with tiny germs that are weak but still alive. When someone is taking teriflunomide, or has just stopped it, their body’s defenses are not as strong. So these vaccines should be avoided during treatment and for at least six months afterward, because the weak germs could still cause an infection.

• Inactivated vaccines are safe to use. These vaccines don’t contain any live germs, so they can’t cause an infection. Examples include regular flu shots and COVID-19 vaccines.

Other Specifications:

• Teriflunomide in Pregnant and Lactating Women: Teriflunomide should be strictly avoided in pregnant and lactating women due to its potential teratogenicity. Teriflunomide should be avoided in breastfeeding mothers as it can harm the fetus.

• Teriflunomide in Patients With Liver Impairment: Teriflunomide can increase the risk of liver failure and death if the drug Teriflunomide is used in patients with liver impairment. So, because of the hepatotoxic nature of the drug, it should be avoided strictly in patients with underlying liver disease.

• Teriflunomide in Patients With Severe Infections: Teriflunomide should be used cautiously in patients with severe infections, lung infections, or bone marrow disease. In such patients, drugs should be initiated only after the infection control is achieved, as it can result in immunosuppression.

Teriflunomide Versus Other Oral MS Options

Here’s how teriflunomide compares to other oral MS medicines.

• Dimethyl Fumarate: This medicine works about the same as other MS medicines for stopping MS attacks, but some studies suggest it may do a better job of preventing attacks over time. Teriflunomide still works well for strong flare-ups.

• Ponesimod: This one has been shown to lower MS attacks and MRI spots (lesions) even more than Teriflunomide.

• Fingolimod: Some studies say it can control MS attacks better than Teriflunomide.

• Siponimod: Siponimod is a medicine used for secondary progressive MS (SPMS), and Teriflunomide is used for relapsing-remitting MS (RRMS).

• Ozanimod: Ozanimod usually works better and has fewer problems than Teriflunomide for people with MS