Aubagio

Teriflunomide is used to prevent episodes of symptoms and slow the worsening of disability in patients with relapsing-remitting forms (course of disease where symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do not function properly and people may experience weakness, numbness, loss of muscle coordination, and problems with vision, speech, and bladder control). Teriflunomide is in a class of medications called immunomodulatory agents. It is thought to work by decreasing inflammation and decreasing the action of immune cells that may cause nerve damage.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Aubagio, there are no specific foods that you must exclude from your diet when receiving this medication.

Before you take Aubagio, tell your doctor if you:

• have liver or kidney problems
• have a fever or infection, or you are unable to fight infections
• have numbness or tingling in your hands or feet that is different from your MS symptoms
• have diabetes
• have had serious skin problems when taking other medicines
• have breathing problems
• have high blood pressure
• are breastfeeding or plan to breastfeed. It is not known if Aubagio passes into your breast milk. You and your doctor should decide if you will take Aubagio or breastfeed. You should not do both at the same time.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using Aubagio and other medicines may affect each other causing serious side effects. Aubagio may affect the way other medicines work, and other medicines may affect how Aubagio works.

Especially tell your doctor if you take medicines that could raise your chance of getting infections, including medicines used to treat cancer or to control your immune system.

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.

Hepatotoxicity

Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for Aubagio because recommended doses of Aubagio and leflunomide result in a similar range of plasma concentrations of Aubagio. Concomitant use of Aubagio with other potentially hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of Aubagio therapy. Monitor ALT levels at least monthly for six months after starting Aubagio. If drug induced liver injury is suspected, discontinue Aubagio and start an accelerated elimination procedure with cholestyramine or charcoal. Aubagio is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking Aubagio.

Risk of Teratogenicity

Based on animal data, Aubagio may cause major birth defects if used during pregnancy. Pregnancy must be excluded before starting Aubagio. Aubagio is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during Aubagio treatment or prior to the completion of an accelerated elimination procedure after Aubagio treatment

Pregnancy: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; healthcare providers and patients are encouraged to report pregnancies by calling 1-800-745-4447, option 2

Contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of potential for fetal harm based on animal data

Women who wish to become pregnant should discontinue use of therapy and undergo accelerated elimination procedure to decrease plasma concentration of teriflunomide to less than 0.02 mg/L (0.02 mcg/mL); effective contraception should be used until is verified that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL), which are expected to have minimal embryofetal risk

If patient becomes pregnant while taking this drug, stop treatment, inform the patient of potential risk to fetus, and perform accelerated drug elimination procedure to achieve plasma concentrations of less than 0.02 mg/L (0.02 mcg/mL); refer patient to obstetrician/gynecologist, preferably experienced in reproductive toxicity, for further evaluation and counseling

To minimize any possible risk, men not wishing to father a child and their female partners should use effective contraception

Lactation: Not known whether drug is excreted in human milk; detected in rat milk following a single oral dose; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

Inform patients of signs and symptoms of anaphylaxis and angioedema and signs and symptoms that may signal a serious skin reaction; inform patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, or hepatic dysfunction) may be drug-related; instruct patients to discontinue therapy and seek immediate medical care should these signs and symptoms occur; discontinue therapy, unless reactions are clearly not drug-related, and begin accelerated elimination procedure immediately; such patients should not be re-exposed to teriflunomide

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

You should not use this medicine if you are allergic to teriflunomide or leflunomide, or if:

• you have severe liver disease; or

• you are also taking leflunomide (Arava).

Do not use teriflunomide if you are pregnant or may become pregnant You will need to have a negative pregnancy test before starting this treatment. Avoid getting pregnant until after you stop taking teriflunomide and undergo a "drug elimination" procedure to help rid your body of this medicine. Stop taking teriflunomide and call your doctor right away if you miss a period or think you might be pregnant.

To make sure teriflunomide is safe for you, tell your doctor if you have:

• a history of liver disease;

• high blood pressure;

• a fever, or uncontrolled infections;

• nerve problems, such as neuropathy caused by diabetes;

• breathing problems;

• a history of tuberculosis; or

• any numbness or tingling that feels different from your MS symptoms.

Use birth control to prevent pregnancy while you are taking this medicine. After you stop taking teriflunomide, continue using birth control until you have received blood tests to make sure the drug has been eliminated from your body.

If you become pregnant while taking teriflunomide or within 2 years after you stop, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of teriflunomide on the baby.

If a man fathers a child during or after teriflunomide treatment, the baby may have birth defects. Use a condom to prevent pregnancy while you are taking this medicine. After your treatment ends, continue using condoms until you have received the medications to help your body eliminate teriflunomide.

It is not known whether teriflunomide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Any unexplained bruising or bleeding.
• Feeling very tired or weak.
• Swollen gland.
• A burning, numbness, or tingling feeling that is not normal.
• Shortness of breath.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• Very bad and sometimes deadly lung problems have happened with this medicine. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.

There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects.

In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions (5.3)].

Do not receive a "live" vaccine while using teriflunomide, and for at least 6 months after you stop taking it. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Aubagio (teriflunomide) affects the immune system and reduces swelling and inflammation in the nervous system.

Aubagio is used to reduce flare-ups in people with relapsing multiple sclerosis (MS).

Aubagio is not a cure for MS.

Use is contraindicated. AU TGA pregnancy category: X US FDA pregnancy category: X Comments: -Use of adequate methods of contraception by both females and males is recommended during and for 2 years after stopping treatment.

Animal studies have shown reproductive toxicity, embryolethality and teratogenicity. There are no controlled data in human pregnancy. This drug has been detected in human semen. Men wanting to father a child should discontinue use and perform an accelerated elimination procedure to decrease the plasma concentration of teriflunomide to less than 0.02 mg/L. Women of childbearing potential should use effective contraception during treatment and after treatment as long as teriflunomide plasma concentration is above 0.02 mg/L. Patients should be advised if there is any delay in onset of menses or any other reason to suspect pregnancy, they must notify a physician immediately for pregnancy testing. If pregnancy is confirmed, the patient should be advised of the risk to the fetus. There is a possibility that rapidly lowering the blood level of teriflunomide, at the first delay of menses, may decrease the risk to the fetus. For women receiving teriflunomide treatment, who wish to become pregnant, the drug should be stopped and an accelerated elimination procedure is recommended in order to more rapidly reach a concentration below 0.02 mg/L. See Warnings section for further information on accelerated elimination. A teriflunomide pregnancy registry has been established. Healthcare providers are encouraged to enroll the patient in this registry if pregnancy occurs during treatment. AU TGA pregnancy category X: Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy. US FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.