In the treatment of tuberculosis and the meningococcal carrier state, a small number of resistant bacteria present among a large population of susceptible organisms may rapidly become dominant. Therefore, bacteriological cultures should be obtained before starting therapy to confirm that the organism is susceptible to rifampicin, and these cultures should be repeated during treatment to monitor the patient’s response. Because resistance to rifampicin can develop quickly, susceptibility testing should be performed if cultures remain positive during treatment. If the test results show resistance to rifampicin and the patient is not responding adequately, the treatment regimen should be changed accordingly.

Rifampicin works by inhibiting the initiation of RNA chain formation in susceptible bacteria. It binds to the beta subunit of DNA-dependent RNA polymerase, thereby blocking RNA transcription and preventing bacterial growth.

Rifampin can be administered by the oral route or by IV infusion. IV doses are the same as those for oral.

Tuberculosis:

• Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV
• Pediatric Patients: 10–20 mg/kg, not to exceed 600 mg/day, oral or IV

It is recommended that oral rifampin be administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water.

Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of shortcourse therapy which is usually continued for 2 months. The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Centers for Disease Control and Prevention recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered.

Following the initial phase, treatment should be continued with rifampin and isoniazid for at least 4 months. Treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive

Rifampicin may increase the metabolism of drugs that are processed by CYP450 enzymes, which can reduce the effectiveness of medicines such as quinidine, phenytoin, and theophylline. When used together with atovaquone, rifampicin may lower atovaquone levels while increasing rifampicin concentrations. Concomitant use of ketoconazole and rifampicin may reduce the serum levels of both drugs. Rifampicin may also decrease the serum concentration of enalaprilat. Its absorption may be reduced when taken with antacids. In addition, the risk of hepatotoxicity may increase when rifampicin is used together with halothane or isoniazid.

Rifampicin is contraindicated in patients with known hypersensitivity to rifampicin, any component of the formulation, or any other rifamycin antibiotic. It is also contraindicated in patients receiving ritonavir-boosted saquinavir, due to the increased risk of severe hepatocellular toxicity.

Rifampicin is further contraindicated in patients taking atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir, because it can significantly reduce the plasma concentrations of these antiviral medicines. This may lead to loss of antiviral effectiveness and/or development of viral resistance.

Rifampicin may cause facial flushing and itching, with or without a rash. A flu-like syndrome may also occur, with symptoms such as fever, chills, headache, dizziness, bone pain, shortness of breath, and general weakness or malaise. Gastrointestinal side effects may include nausea, vomiting, loss of appetite, diarrhea, and epigastric discomfort. Other possible adverse effects include pseudomembranous colitis, eosinophilia, leucopenia, haemolytic anaemia, changes in kidney function, renal failure, menstrual disturbances, oedema, myopathy, and muscular weakness. Rifampicin may also cause an orange-red discoloration of urine, faeces, sweat, saliva, sputum, tears, and other body fluids. With prolonged intravenous infusion, thrombophlebitis, local irritation, and inflammation may occur. In rare cases, eye irritation, visual disturbances, anaphylaxis, or shock may develop.

Pregnancy: When rifampicin is given during the last few weeks of pregnancy, it may cause postnatal haemorrhage in both the mother and the newborn. In such cases, treatment with vitamin K may be necessary.

Nursing mothers: Because animal studies have shown a potential risk of tumorigenicity with rifampicin, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the medicine to the mother.

Rifampicin has been associated with liver dysfunction, and fatal cases linked to jaundice have been reported in patients with pre-existing liver disease or in those receiving rifampicin together with other hepatotoxic medicines. Therefore, patients with impaired liver function should receive rifampicin only when clearly necessary, and then with great caution under close medical supervision. In such patients, liver function should be carefully monitored before starting treatment and regularly during therapy, especially SGPT/ALT and SGOT/AST, which should be checked prior to treatment and then every 2 to 4 weeks during therapy. If signs of hepatocellular injury develop, rifampicin should be discontinued.

In some cases, hyperbilirubinemia may occur during the early days of treatment due to competition between rifampicin and bilirubin for excretory pathways in the liver at the cellular level. A single report of a moderate increase in bilirubin and/or transaminase levels does not by itself require discontinuation of therapy. Instead, the tests should be repeated, trends in the results should be assessed, and the findings should be interpreted together with the patient’s clinical condition.

Rifampicin also has enzyme-inducing properties, including the induction of delta-aminolevulinic acid synthetase. There have been isolated reports suggesting that rifampicin may worsen porphyria.

Geriatric use: Clinical studies of rifampicin did not include enough patients aged 65 years and older to determine clearly whether they respond differently from younger patients. However, other clinical experience has not shown any major difference in response between elderly and younger patients. Even so, rifampicin should be used with caution in elderly patients.

In case of overdose, symptoms such as nausea, vomiting, abdominal pain, itching, headache, and increasing lethargy may appear shortly after ingestion. In severe cases, especially in patients with significant liver disease, unconsciousness may occur. Temporary increases in liver enzymes and/or bilirubin levels may also be seen.

Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces may occur, and the intensity of this discoloration is usually related to the amount of drug taken. Severe overdose may lead to liver enlargement, sometimes with tenderness, within a few hours. Bilirubin levels may rise, and jaundice may develop rapidly. Liver-related complications may be more severe in patients with pre-existing liver impairment.

Other physical findings are generally normal, and a direct effect on the blood-forming system, electrolyte levels, or acid-base balance is considered unlikely. In pediatric patients, facial or periorbital edema has also been reported. In some fatal cases, hypotension, sinus tachycardia, ventricular arrhythmias, seizures, and cardiac arrest have been observed.

Anti-Tubercular Antibiotics.

Store at 15°C to 30°C. Protect from light and avoid excessive heat.