Rifampin, isoniazid, and pyrazinamide

RIFATER is a combination of the three drugs, rifampin, isoniazid, and pyrazinamide. Each of these individual drugs has been associated with liver dysfunction.

Systemic hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, may occur in patients receiving RIFATER (See ADVERSE REACTIONS). Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia, elevated liver transaminases or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills, aches, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). These reactions may be severe and DRESS may be fatal. Manifestations of hypersensitivity, such as fever, lymphadenopathy or laboratory abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. Monitor patients receiving RIFATER for signs and/or symptoms of hypersensitivity reactions. If these signs or symptoms occur, discontinue RIFATER and administer supportive measures.

Rifampin

Rifampin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Because RIFATER contains both rifampin and isoniazid, it should only be given with caution and under strict medical supervision to patients with impaired liver function. In these patients, careful monitoring of liver function, especially serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, RIFATER should be withdrawn.

In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels, and considering them in conjunction with the patient’s clinical condition.

Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin administration.

Isoniazid

(See BOX WARNING.)

Since RIFATER contains isoniazid, ophthalmologic examinations (including ophthalmoscopy) should be done before treatment is started and periodically thereafter, even without occurrence of visual symptoms.

Severe cutaneous reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), some with a fatal outcome, have been reported with the use of isoniazid (see ADVERSE REACTIONS). Monitor for skin reactions and advise patients to report skin rashes or mucosal lesions immediately. Discontinue RIFATER if these reactions occur.

Pyrazinamide

Since RIFATER contains pyrazinamide, patients started on RIFATER should have baseline serum uric acid and liver function determinations. Patients with preexisting liver disease or those patients at increased risk for drug related hepatitis (e.g., alcohol abusers) should be followed closely.

Because it contains pyrazinamide, RIFATER should be discontinued and not be resumed if signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear. If hyperuricemia accompanied by an acute gouty arthritis occurs without liver dysfunction, the patient should be transferred to a regimen not containing pyrazinamide.

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

• If you have an allergy to rifampin, isoniazid, pyrazinamide, or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Gout or liver problems.
• If you have had very bad side effects while taking isoniazid in the past, like liver problems, drug fever, chills, or arthritis.
• If you had liver problems while taking some other drug in the past.
• If you are taking any of these drugs: Atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with rifampin, isoniazid, and pyrazinamide.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• Take with a full glass of water.
• To gain the most benefit, do not miss doses.
• Keep taking rifampin, isoniazid, and pyrazinamide as you have been told by your doctor or other health care provider, even if you feel well.
• Do not take antacids within 1 hour of this medicine.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Change in color of body fluids to orange or red.
• Loose stools (diarrhea).
• Dizziness.
• Feeling sleepy.
• Gas.
• Headache.
• Heartburn.
• Upset stomach or throwing up.
• Belly pain.
• Not able to sleep.
• Anxiety.
• Not hungry.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about rifampin, isoniazid, and pyrazinamide, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about rifampin, isoniazid, and pyrazinamide. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using rifampin, isoniazid, and pyrazinamide.

Review Date: October 4, 2017