Pronunciation:

le-FLOO-noe-mide

Brand Names:

• Arava

Dosage Forms:

• Tablet

Warnings:

Leflunomide is contraindicated in pregnant women due to potential for fetal harm. Pregnancy must be excluded before the start of treatment and must be avoided during treatment or prior to the completion of the accelerated drug elimination procedure after treatment with leflunomide. Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide. Do not use in patients with acute or chronic liver disease or an ALT greater than 2 times the ULN, and ALT monitoring is recommended after starting leflunomide. Stop leflunomide and use an accelerated drug elimination procedure if pregnancy occurs or leflunomide-induced liver injury is suspected .

Classifications:

Therapeutic—

Immune Suppressant

Pharmacologic—

Dihydroorotate Dehydrogenase Inhibitor

Uses of This Medicine:

Leflunomide is used to relieve symptoms caused by active rheumatoid arthritis, such as inflammation, swelling, stiffness, and joint pain. This medicine works by stopping the body from producing too many of the immune cells that are responsible for the swelling and inflammation.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of leflunomide in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of leflunomide in the elderly. However, elderly patients are more likely to have age-related nerve problems, which may require caution in patients receiving leflunomide.

Breast-feeding—

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Teriflunomide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acyclovir
• Adenovirus Vaccine
• Atorvastatin
• Baricitinib
• Bosentan
• Cefaclor
• Ciprofloxacin
• Dabrafenib
• Dasabuvir
• Dengue Tetravalent Vaccine, Live
• Elagolix
• Enzalutamide
• Furosemide
• Glyburide
• Grazoprevir
• Influenza Virus Vaccine, Live
• Irinotecan
• Letermovir
• Levoketoconazole
• Measles Virus Vaccine, Live
• Methotrexate
• Montelukast
• Mumps Virus Vaccine, Live
• Paclitaxel
• Pexidartinib
• Pitavastatin
• Poliovirus Vaccine, Live
• Repaglinide
• Revefenacin
• Rosuvastatin
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Simvastatin
• Smallpox Vaccine
• Sulfasalazine
• Tenofovir Alafenamide
• Topotecan
• Valacyclovir
• Varicella Virus Vaccine, Live
• Warfarin
• Yellow Fever Vaccine
• Zoster Vaccine, Live

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood or bone marrow problems, history of or
• Bone marrow dysplasia or
• Immune system problem or
• Infection, severe or uncontrolled or
• Tuberculosis, history of or
• Weak immune system—Use is not recommended in patients with these conditions.

• Diabetes or
• Nerve problems—May increase your risk for more serious side effects.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Liver disease, severe—Should not be used in patients with these condition.

• Lung disease (eg, interstitial lung disease), history of—Use with caution. May make this condition worse.

Proper Use of This Medicine:

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For rheumatoid arthritis:
    • Adults—
      • For patients who are at low-risk for liver disease and bone marrow problems caused by Arava®: At first, 100 milligrams (mg) once a day for 3 days, then 20 mg once a day. Your doctor may adjust the dose as needed. Your doctor may adjust your dose as needed and tolerated.
      • For patients who are at high-risk for liver disease and bone marrow problems caused by Arava®: 20 mg once a day. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

You will need to have your blood pressure measured before starting this medicine and while you are using it. If you notice any change to your recommended blood pressure, call your doctor right away. If you have questions about this, talk to your doctor.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Leflunomide may also cause birth defects if the father is using it when his sexual partner becomes pregnant. Men taking leflunomide should use condoms as a form of birth control during sexual intercourse. A man intending to father a child should stop taking this medicine and check with his doctor right away.

Do not use this medicine if you are also using teriflunomide. Using these medicines together may cause unwanted serious side effects.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Leflunomide can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may cause drug reaction with eosinophilia and systemic reactions (DRESS), including serious skin reactions. Check with your doctor right away if you have any blistering, peeling, or loose skin, chills, itching, joint or muscle pain, red skin lesions, often with a purple center, sores, ulcers, or white spots in the mouth or on the lips, or unusual tiredness or weakness.

You will need to have a skin test for tuberculosis before you start using this medicine. Tell your doctor if you or anyone in your home has ever had a positive reaction to a tuberculosis test.

Using this medicine may increase your risk of getting serious infections or cancer. Talk to your doctor if you have concerns about this risk.

Check with your doctor right away if you are having burning, numbness, tingling, or painful sensations in the arms, hands, legs, or feet. These could be symptoms of a condition called peripheral neuropathy.

Check with your doctor right away if you have a cough with or without a fever, shortness of breath, or any difficulty with breathing.

While you are being treated with leflunomide, and after you stop using it, do not have any vaccinations without your doctor's approval. Live virus vaccines should not be given while receiving this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Bloody or cloudy urine

cough

difficult or painful breathing

difficult, burning, or painful urination

dizziness

fever

frequent urge to urinate

headache

loss of appetite

nausea or vomiting

sneezing

sore throat

tightness in the chest

yellow eyes or skin

Less common

Burning feeling in the chest or stomach

burning, prickling, or tingling sensation in the fingers or toes

chest pain

diarrhea

fast or pounding heartbeat

indigestion

joint or muscle pain or stiffness

severe stomach pain

tenderness in the stomach area

unusual tiredness or weakness

Incidence not known

Area rash

black or tarry stools

bleeding gums

blistering, peeling, or loosening of the skin

bloating

blood in the stools

burning, numbness, tingling, or painful sensations

chills

clay-colored stools

confusion

constipation

continuing vomiting

cough or hoarseness

dark urine

fainting

fever with or without chills

general feeling of tiredness or weakness

high fever

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

light-colored stools

lightheadedness

lower back or side pain

pains in the stomach, side, or abdomen, possibly radiating to the back

pale skin

pinpoint red spots on the skin

rapid, shallow breathing

red skin lesions, often with a purple center

red, irritated eyes

sores, ulcers, or white spots in the mouth or on the lips

swollen glands

unexplained bleeding or bruising

unpleasant breath odor

unsteadiness or awkwardness

unusual bleeding or bruising

upper right abdominal or stomach pain

vomiting of blood

weakness in the arms, hands, legs, or feet

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Back pain

hair loss

heartburn

skin rash

stomach pain

weight loss (unexplained)

Less common

Acne

anxiety

decreased appetite

dry mouth

gas

irritation or soreness of the mouth

itching of the skin

pain or burning in the throat

runny nose

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.