Rifampin-Isoniazid-Pyrazinamide discontinued

Rifampin-Isoniazid-Pyrazinamide is a combination medication used in the initial phase of the short-course treatment (i.e., 2 months) of pulmonary tuberculosis. 

• Rifampin-Isoniazid-Pyrazinamide is available under the following different brand names: Rifater (DSC)

Common side effects of Rifampin-Isoniazid-Pyrazinamide include:

• Red discoloration of the teeth, sweat, urine, saliva, and tears,
• Nausea,
• Vomiting,
• Stomach pain,
• Mild rash,
• Itching, and
• Joint or muscle pain

Serious side effects of Rifampin-Isoniazid-Pyrazinamide include:

• Hives,
• Difficulty breathing,
• Swelling in the face or throat,
• Fever,
• Sore throat,
• Burning in your eyes,
• Skin pain,
• Red or purple skin rash that spreads and causes blistering and peeling,
• Skin rash,
• Swollen glands,
• Muscle aches,
• Severe weakness,
• Unusual bruising,
• Joint pain or stiffness,
• Nausea,
• Vomiting,
• Upper stomach pain,
• Weakness,
• Tiredness,
• Loss of appetite,
• Yellowing of your skin or eyes (jaundice),
• Numbness, tingling, or burning pain in the hands or feet,
• Vision problems,
• Pain behind your eyes,
• Wheezing,
• Severe stomach pain, and
• Diarrhea that is watery or bloody.

Rare side effects of Rifampin-Isoniazid-Pyrazinamide include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 120 mg/50 mg/300 mg

Tuberculosis

• Below 44 kg: 4 tablets orally once a day
• 44-54 kg: 5 tablets orally once a day
• Above 55 kg: 6 tablets orally once a day
• Following the initial phase dosing with Rifampin/isoniazide for at least 4 months; continue longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is positive for HIV infection.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Rifampin-Isoniazid-Pyrazinamide has severe interactions with at least 56 other drugs.
• Rifampin-Isoniazid-Pyrazinamide has serious interactions with at least 280 other drugs.
• Rifampin-Isoniazid-Pyrazinamide has moderate interactions with at least 341 other drugs.
• Rifampin-Isoniazid-Pyrazinamide has minor interactions with at least 126 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to isoniazid, pyrazinamide, rifamycins
• Acute liver disease, severe hepatic damage, acute gout
• Rifampin is contraindicated in patients receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity.
• Many CYP substrates are contraindicated with rifampin owing to the risk of decreased systemic exposure.
• Rifampin is contraindicated with atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir because of the potential to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy for HIV infection and/or development of viral resistance

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Rifampin-Isoniazid-Pyrazinamide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Rifampin-Isoniazid-Pyrazinamide?”

Cautions

• Systemic hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, may occur; signs and symptoms 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, palpitation. reactions may be severe and fatal; monitor for signs and/or symptoms of hypersensitivity reactions; discontinue therapy and administer supportive measures if symptoms occur
• Rifampin is not recommended for intermittent therapy; caution patient against intentional or accidental interruption of daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases
• Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D
• Patient should be told that rifampin may produce a discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears, and should be forewarned of this; soft contact lenses may be permanently stained
• Heartburn, epigastric distress, anorexia, nausea, vomiting, jaundice, flatulence, cramps, and diarrhea were reported; although Clostridium difficile was shown in vitro to be sensitive to rifampin, pseudomembranous colitis reported with the use of rifampin (and other broad-spectrum antibiotics); consider this diagnosis in patients who develop diarrhea in association with antibiotic use
• Isoniazid has some monoamine oxidase inhibiting activity; interaction with tyramine-containing foods (cheese, red wine) may occur; diamine oxidase may also be inhibited, causing exaggerated response (.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (.g., skipjack, tuna, other tropical fish); tyramine and histamine- containing foods should be avoided in patients receiving therapy
• The reliability of oral or other systemic hormonal contraceptives may be affected by rifampin; consideration should be given to using alternative contraceptive measures
• Patients should abstain from alcohol, hepatotoxic medications, or herbal products while receiving therapy
• Emphasize compliance with a full course of therapy and stress the importance of not missing any doses
• Monitor for symptoms and clinical/laboratory signs of liver injury, especially if treatment is prolonged or given with other hepatotoxic drugs; patients with impaired liver function should be given rifampin only in cases of necessity and then under strict medical supervision; carefully monitor liver function in these patients before therapy and then every 2- 4 weeks during therapy; if signs of hepatic damage occur or worsen, discontinue rifampin
• Cases of severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthemata’s pustulosis (AGEP), reported; if symptoms or signs of severe cutaneous adverse reactions develop, discontinue immediately and institute appropriate therapy
• Rifampin may cause vitamin K–dependent coagulation disorders and bleeding; monitor coagulation tests during rifampin treatment (prothrombin time and other coagulation tests) in patients at risk of vitamin K deficiency (such as those with chronic liver disease, poor nutritional status, on prolonged antibacterial drugs or anticoagulants); consider discontinuation of therapy if abnormal coagulation tests and/or bleeding occur; supplemental vitamin K administration should be considered when appropriate
• Postmarketing reports suggest that concomitant administration of high doses of cefazolin and rifampin may prolong prothrombin time, leading to severe vitamin K–dependent coagulation disorders that may be life-threatening or fatal; avoid concomitant use of cefazolin and rifampin in patients at increased risk for bleeding; if no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated.
• Drug interaction overview
  • Isoniazid is known to inhibit certain cytochrome P-450 enzymes (.g, CYP1A2, CYP2C9, CYP2C19, CYP3A4); concomitant use may decrease the elimination of drugs metabolized by these enzymes which may increase the risk of toxicities of these drugs; adjust dosages of drugs metabolized by these enzymes based on approved drug labeling and if applicable, therapeutic drug monitoring;
  • isoniazid has been reported to inhibit the metabolism of the following drugs: anticonvulsants (.g, carbamazepine, phenytoin, primidone, valproic acid), benzodiazepines (.g, diazepam), haloperidol, ketoconazole, theophylline, and warfarin; therefore, isoniazid may increase risk of toxicities of these drugs
  • As the drug combination contains both isoniazid (inhibitor) and rifampin (inducer), the effect on the metabolism of the above-listed drugs when used concomitantly with the drug combination is unknown; potential for increased toxicity cannot be excluded; monitor closely for adverse reactions.

Pregnancy and Lactation

• Isoniazid: embryocidal effects were reported in both rats and rabbits, although no congenital abnormalities were observed in mammalian offspring when given during pregnancy
• Pyrazinamide: Animal reproductive studies have not been conducted
• Rifampin
• No adequate and well-controlled studies have been performed in pregnant women; is teratogenic in rodents.
• Rifampin has been reported to cross the placental barrier and appear in cord blood.
• When administered during the last few weeks of pregnancy, rifampin can cause postnatal hemorrhages in the mother and infant for which treatment with vitamin K may be indicated.
• Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Lactation
  • Isoniazid is known to be secreted into breast milk.
  • Because of the potential for tumorigenicity shown for rifampin in animal studies, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother