• Antibacterial, antimycobacterial

Rifampin, isoniazid, pyrazinamide, and ethambutol (rif-AM-pin, eye-soe-NYE-a-zid, peer-a-ZIN-a-mide, and e-THAM-byoo-tole) is a combination anti-infective medicine. This combination medicine is used to treat tuberculosis (TB). It may be taken alone or with one or more of other medicines for TB.

To help clear up your tuberculosis (TB) infection completely, you must keep taking this medicine for the full time of treatment, even if you begin to feel better. This is very important. It is also important that you do not miss any doses.

Rifampin, isoniazid, pyrazinamide, and ethambutol combination is available only with your doctor's prescription, in the following dosage form:

Oral
• Tablets

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 rifampin, isoniazid, pyrazinamide, and ethambutol combination, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to ethionamide (e.g., Trecator-SC), pyrazinamide, niacin (e.g., Nicobid, nicotinic acid), rifampin (e.g., Rifadin), rifabutin (e.g., Mycobutin), rifapentine (e.g., Priftin), isoniazid (e.g., INH, Nydrazid), or ethambutol (e.g., Myambutol). Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Pregnant women with tuberculosis (TB) should be treated with TB medicines, including rifampin, isoniazid, pyrazinamide, and ethambutol. Rifampin, isoniazid, pyrazinamide, and ethambutol combination has not been shown to cause birth defects or other problems in humans. However, rifampin can rarely cause bleeding in newborn babies and mothers when taken during the last weeks of pregnancy. Also, studies in rats and mice have shown that rifampin given in high doses causes birth defects, usually backbone problems (spina bifida) and cleft palate.

Breast-feeding—Rifampin, isoniazid, pyrazinamide, and ethambutol pass into the breast milk. However, rifampin, isoniazid, pyrazinamide, and ethambutol have not been reported to cause problems in nursing babies.

Children—Rifampin, isoniazid, pyrazinamide, and ethambutol combination may not be appropriate for use in children weighing under 30 kilograms (kg) (66 pounds).

Older adults—Liver problems are more likely to occur in patients over 50 years of age who are taking isoniazid-containing medicines.

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 rifampin, isoniazid, pyrazinamide, and ethambutol combination, it is especially important that your health care professional know if you are taking any of the following:

• Acetaminophen (e.g., Tylenol) (with long-term, high-dose use) or
• Alfentanil (e.g., Alfenta) or
• Amiodarone (e.g., Cordarone) or
• Anabolic steroids (nandrolone [e.g., Anabolin], oxandrolone [e.g., Anavar], oxymetholone [e.g., Anadrol], stanozolol [e.g., Winstrol]) or
• Androgens (male hormones) or
• Antithyroid agents (medicine for overactive thyroid) or
• Carbamazepine (e.g., Tegretol)
• Carmustine (e.g., BiCNU) or
• Chloroquine (e.g., Aralen) or
• Dantrolene (e.g., Dantrium) or
• Daunorubicin (e.g., Cerubidine) or
• Divalproex (e.g., Depakote) or
• Etretinate (e.g., Tegison) or
• Gold salts (medicine for arthritis) or
• Hydroxychloroquine (e.g., Plaquenil) or
• Mercaptopurine (e.g., Purinethol) or
• Methyldopa (e.g., Aldomet) or
• Naltrexone (e.g., Trexan) (with long-term, high-dose use) or
• Phenothiazines (acetophenazine [e.g., Tindal], chlorpromazine [e.g., Thorazine], fluphenazine [e.g., Prolixin], mesoridazine [e.g., Serentil], perphenazine [e.g., Trilafon], prochlorperazine [e.g., Compazine], promazine [e.g., Sparine], promethazine [e.g., Phenergan], thioridazine [e.g., Mellaril], trifluoperazine [e.g., Stelazine], triflupromazine [e.g., Vesprin], trimeprazine [e.g., Temaril]) or
• Plicamycin (e.g., Mithracin) or
• Valproic acid (e.g., Depakene)—These medicines may increase the chance of liver damage if taken with rifampin, isoniazid, and pyrazinamide combination

• Aminophylline (e.g., Somophyllin) or
• Amprenavir (e.g., Agenerase) or
• Anticoagulants (blood thinners) or
• Antidiabetics, oral (diabetes medicines you take by mouth) or
• Chloramphenicol or
• Corticosteroids (cortisone-like medicine) or
• Delavirdine (e.g., Rescriptor) or
• Digitalis glycosides (heart medicine) or
• Disopyramide (e.g., Norpace) or
• Efavirenz (e.g., Sustiva) or
• Estramustine (e.g., Emcyt) or
• Fluconazole (e.g., Diflucan) or
• Indinavir (e.g., Crixivan) or
• Itraconazole (e.g., Sporanox) or
• Ketoconazole (e.g., Nizoral) or
• Methadone (e.g., Dolophine) or
• Methotrexate (e.g., Mexate) or
• Mexiletine (e.g., Mexitil) or
• Nelfinavir (e.g., Viracept) or
• Nevirapine (e.g., Viramune) or
• Oxtriphylline (e.g., Choledyl) or
• Quinidine (e.g., Quinidex) or
• Ritonavir (e.g., Norvir) or
• Saquinavir (e.g., Fortovase, Invirase) or
• Theophylline (e.g., Theo-Dur, Somophyllin-T) or
• Tocainide (e.g., Tonocard) or
• Verapamil (e.g., Calan)—Rifampin, isoniazid, pyrazinamide, and ethambutol combination may decrease the effects of these medicines

• Disulfiram (e.g., Antabuse)—This medicine may increase the chance of liver damage and side effects, such as dizziness, lack of coordination, irritability, and inability to sleep

• Estrogens (female hormones) or
• Oral contraceptives (birth control pills) containing estrogen or
• Phenytoin (e.g., Dilantin)—Rifampin, isoniazid, pyrazinamide, and ethambutol combination may decrease the effects of these medicines. If you are taking oral contraceptives, this may increase the chance of pregnancy. These medicines may also increase the chance of liver damage if taken with rifampin, isoniazid, pyrazinamide, and ethambutol combination

• Alcohol abuse (or history of) or
• Liver disease—There may be an increased chance of getting hepatitis if you take this medicine and drink alcohol daily

• Convulsive disorders such as seizures or epilepsy—This medicine may increase the frequency of convulsions (seizures) in some patients

• Gout (history of)—This medicine may worsen or cause a gout attack in patients with a history of gout

• Kidney disease (severe)—There may be an increased chance of side effects in patients with severe kidney disease

If this medicine upsets your stomach, take it with food. Antacids may also help. However, do not take aluminum-containing antacids within 1 hour of the time you take rifampin, isoniazid, pyrazinamide, and ethambutol combination. They may keep this medicine from working properly.

To help clear up your tuberculosis (TB) completely, it is very important that you keep taking this medicine for the full time of treatment, even if you begin to feel better after a few weeks. It is important that you do not miss any doses.

Your doctor may also want you to take pyridoxine (e.g., Hexa-Betalin, vitamin B₆) every day to help prevent or lessen some of the side effects of isoniazid. If it is needed, it is very important to take pyridoxine every day along with this medicine. Do not miss any doses.

Dosing—

The dose of rifampin, isoniazid, pyrazinamide, and ethambutol combination 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 rifampin, isoniazid, pyrazinamide, and ethambutol combination. If your dose is different, do not change it unless your doctor tells you to do so.

• For oral dosage form (tablets):
  • For the treatment of tuberculosis:
    • Adults weighing between 30 and 37 kilograms (kg) (66 and 82 pounds)—2 tablets once a day.
    • Adults weighing between 38 and 54 kg (83 and 120 pounds)—3 tablets once a day.
    • Adults weighing between 55 and 70 kg (121 and 155 pounds)—4 tablets once a day.
    • Adults weighing 71 kilograms (kg) (156 pounds) or more—5 tablets once a day.
    • Children weighing 30 kg (66 pounds) or more—See adult doses.
    • Children weighing under 30 kg (66 pounds)—Use is not recommended.

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. If rifampin, isoniazid, pyrazinamide, and ethambutol combination is taken on an irregular schedule, side effects may occur more often and may be more serious than usual. If you have any questions about this, check with your health care professional.

Storage—

To store this medicine:

• Keep out of the reach of children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

It is very important that your doctor check your progress at regular visits. In addition, you should check with your doctor immediately if blurred vision or loss of vision, with or without eye pain, occurs during treatment. He or she may want you to have your eyes checked by an ophthalmologist (eye doctor).

If your symptoms do not improve within 2 to 3 weeks, or if they become worse, check with your doctor.

Oral contraceptives (birth control pills) containing estrogen may not work properly if you take them while you are taking rifampin, isoniazid, pyrazinamide, and ethambutol combination. Unplanned pregnancies may occur. You should use a different method of birth control while you are taking this medicine. If you have any questions about this, check with your health care professional.

Liver problems may be more likely to occur if you drink alcoholic beverages regularly while you are taking this medicine. Also, the regular use of alcohol may keep this medicine from working properly. Therefore, you should strictly limit the amount of alcoholic beverages you drink while you are taking this medicine.

Certain foods such as cheese (Swiss or Cheshire) or fish (tuna, skipjack, or Sardinella) may rarely cause reactions in some patients taking isoniazid-containing medicines. Check with your doctor if redness or itching of the skin, hot feeling, fast or pounding heartbeat, sweating, chills or clammy feeling, headache, or lightheadedness occurs while you are taking this medicine.

This medicine will cause urine, stool, saliva, sputum, sweat, and tears to turn reddish-orange to reddish-brown. This is to be expected while you are taking this medicine. This effect may cause soft contact lenses to become permanently discolored. Standard cleaning solutions may not take out all the discoloration. Therefore, it is best not to wear soft contact lenses while taking this medicine. Hard contact lenses are not discolored by this medicine. This condition will return to normal once you stop taking this medicine. If you have any questions about this, check with your health care professional.

If this medicine causes you to feel very tired or very weak; or causes clumsiness; unsteadiness; a loss of appetite; nausea; numbness, tingling, burning, or pain in the hands and feet; or vomiting, stop taking it and check with your doctor immediately. These may be early warning symptoms of more serious liver or nerve problems that could develop later.

Rifampin, isoniazid, pyrazinamide, and ethambutol combination may cause blood problems. These problems may result in a greater chance of certain infections, slow healing, and bleeding of the gums. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks. Dental work should be delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.

For diabetic patients: This medicine may cause false test results with urine ketone tests. Check with your doctor before changing your diet or the dosage of your diabetes 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
  • Clumsiness or unsteadiness;  dark urine ;  loss of appetite;  nausea and vomiting;  numbness, tingling, burning, or pain in hands and feet;  unusual tiredness or weakness ;  yellow eyes or skin 
  
  

• Less common
  • Chills;  difficulty in breathing;  dizziness;  fever;  headache;  itching;  muscle and bone pain;  pain in large and small joints;  redness of skin;  shivering;  skin rash 
  
  

• Rare
  • Bloody or cloudy urine;  blurred vision or loss of vision, with or without eye pain;  convulsions (seizures);  greatly decreased frequency of urination or amount of urine;  mental depression;  mood or mental changes;  sore throat ;  unusual bleeding or bruising 
  
  

Other 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. However, check with your doctor if any of the following side effects continue or are bothersome.

• More Common
  • Diarrhea;  stomach pain 
  
  

• Less common
  • Sore mouth or tongue 
  
  

  This medicine commonly causes urine, stool, saliva, sputum, sweat, and tears to turn reddish-orange to reddish-brown. This side effect does not usually require medical attention.

  Dark urine and yellowing of the eyes or skin (signs of liver problems) caused by isoniazid are more likely to occur in patients 50 years of age and older.

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