Chemical formula: C₄₃H₅₈N₄O₁₂ Molecular mass: 822.94 g/mol PubChem compound: 5381226
Rifampicin interacts in the following cases:
Rifampicin are a well characterized and potent inducer of drug metabolizing enzymes and transporters. Enzymes and transporters reported to be affected by rifampicin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways, and these pathways may be induced by rifampicin simultaneously. Therefore, rifampicin may accelerate the metabolism and reduce the activity of certain co-administered drugs, and has the potential to perpetuate clinically important drug-drug interactions against many drugs and across many drug classes. To maintain optimum therapeutic blood levels, dosages of drugs may require adjustment when starting or stopping concomitantly administered rifampicin.
A daily dose of 8 mg/kg should not be exceeded in patients with impaired liver function.
Patients with impaired liver function should only be given rifampicin in cases of necessity, and then with caution and under close medical supervision. In these patients, lower doses of rifampicin are recommended and careful monitoring of liver function, especially serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) should initially be carried out prior to therapy, weekly for two weeks, then every two weeks for the next six weeks. If signs of hepatocellular damage occur, rifampicin should be withdrawn.
Rifampicin should also be withdrawn if clinically significant changes in hepatic function occur. The need for other forms of antituberculosis therapy and a different regimen should be considered. Urgent advice should be obtained from a specialist in the management of tuberculosis. If rifampicin is re-introduced after liver function has returned to normal, liver function should be monitored daily.
In patients with impaired liver function, elderly patients, malnourished patients, and possibly, children under two years of age, caution is particularly recommended when instituting therapeutic regimens in which isoniazid is to be used concurrently with rifampicin. If the patient has no evidence of pre-existing liver disease and normal pre-treatment liver function, liver function tests need only be repeated if fever, vomiting, jaundice or other deterioration in the patient’s condition occur.
Concomitant antacid administration may reduce the absorption of rifampicin. Daily doses of rifampicin should be given at least 1 hour before the ingestion of antacids.
Antidiabetic (e.g. chlorpropamide, tolbutamide, sulfonylureas, rosiglitazone): diabetes may become more difficult to control.
Rifampicin treatment reduces the systemic exposure of oral contraceptives. Patients on oral contraceptives should be advised to use alternative, non-hormonal methods of birth control during rifampicin therapy. Also diabetes may become more difficult to control.
Hepatitis-C antiviral drugs (e.g, daclatasvir, simeprevir, sofosbuvir, telaprevir): Concurrent use of treatment of hepatitis-C antiviral drugs and rifampicin should be avoided.
If p-aminosalicylic acid and rifampicin are both included in the treatment regimen, they should be given not less than eight hours apart to ensure satisfactory blood levels.
When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.
The concomitant use of rifampicin with other antibiotics causing vitamin K dependent coagulopathy such as cefazolin (or other cephalosporins with N-methyl-thiotetrazole side chain) should be avoided as it may lead to severe coagulation disorders, which may result in fatal outcome (especially in high doses).
Increases active metabolite exposure. Rifadin strongly induces CYP2C19, resulting in both an increased level of clopidogrel active metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a precaution, concomitant use of clopidogrel and rifampicin should be discouraged.
Rifampicin has also been shown to increase the clearance of dapsone and the production of the hydroxylamine metabolite of dapsone which could increase the risk of methaemoglobinaemia, haemolytic anaemia, agranulocytosis, and haemolysis.
Decrease enalapril active metabolite exposure. Dosage adjustments should be made if indicated by the patient’s clinical condition.
When rifampicin is given concomitantly with halothane, the potential for hepatotoxicity is increased. The concomitant use of rifampicin and halothane should be avoided.
When rifampicin is given concomitantly with isoniazid, the potential for hepatotoxicity is increased. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.
Concurrent use of ketoconazole and rifampicin has resulted in decreased serum concentrations of both drugs.
Plasma concentrations of morphine may be reduced by rifampicin. The analgesic effect of morphine should be monitored and doses of morphine adjusted during and after treatment of rifampicin.
Concomitant use of paracetamol with rifampicin may increase the risk of hepatotoxicity.
At very high doses in animals rifampicin has been shown to have teratogenic effects. There are no well controlled studies with rifampicin in pregnant women. Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin, alone or in combination with other antituberculosis drugs, on the human foetus is not known. Therefore, rifampicin should be used in pregnant women or in women of child bearing potential only if the potential benefit justifies the potential risk to the foetus. When rifampicin is administered during the last few weeks of pregnancy it may cause post-natal haemorrhages in the mother and infant for which treatment with Vitamin K1 may be indicated.rifampicin
Rifampicin is excreted in breast milk, patients receiving rifampicin should not breast feed unless in the physician’s judgement the potential benefit to the patient outweighs the potential risk to the infant.
No studies on the effects on the ability to drive and use machines have been performed.
The following CIOMS frequency rating is used, when applicable: Very common ≥10%; Common ≥1 and <10%; Uncommon ≥0.1 and <1%; Rare ≥0.01 and <0.1%; Very rare <0.01%, Unknown (cannot be estimated from available data).
Rifampicin for infusion is generally well tolerated and accepted by patients, although hypersensitivity reactions have been described and occasionally patients have experienced fever, skin rashes and nausea/vomiting.
Occasional instances of phlebitis and pain at the infusion site have been reported.
Reactions occurring with either daily or intermittent dosage regimens include:
Unknown: Pseudomembranous colitis, Influenza
Common: Thrombocytopenia with or without purpura, usually associated with intermittent therapy, but is reversible if drug is discontinued as soon as purpura occurs.
Uncommon: Leukopenia
Unknown: Disseminated intravascular coagulation, Eosinophilia, Agranulocytosis, Hemolytic anemia, Vitamin K dependent coagulation disorders
Unknown: Anaphylactic reaction
Unknown: Adrenal insufficiency in patients with compromised adrenal function have been observed
Unknown: Decreased appetite
Unknown: Psychotic disorder
Common: Headache, Dizziness
Unknown: Cerebral hemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura
Unknown: Tear discolouration
Unknown: Shock, Flushing, Vasculitis, Bleeding
Unknown: Dyspnoea, Wheezing, Sputum discoloured
Common: Nausea, Vomiting
Uncommon: Diarrhea
Unknown: Gastrointestinal disorder, Abdominal discomfort, Tooth discolouration (which may be permanent)
Unknown: Hepatitis, Hyperbilirubinaemia
Unknown: Erythema multiforme, Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), Drug reaction with eosinophilia and systemic symptoms (DRESS), Acute generalized exanthematous pustulosis (AGEP), Skin reaction, Pruritus, Rash pruritic, Urticaria, Dermatitis allergic, Pemphigoid, Sweat discoloration
Unknown: Muscle weakness, Myopathy, Bone pain
Unknown: Acute kidney injury usually due to renal tubular necrosis or tubulointerstitial nephritis, Chromaturia
Unknown: Post-partum haemorrhage, Fetal-maternal haemorrhage
Unknown: Menstrual disorder
Unknown: Porphyria
Very common: Pyrexia, Chills
Common: Paradoxical drug reaction (Recurrence or appearance of new symptoms of tuberculosis, physical and radiological signs in a patient who had previously shown improvement with appropriate antituberculosis treatment is called a paradoxical reaction, which is diagnosed after excluding poor compliance of the patient to treatment, drug resistance, side effects of antitubercular therapy, secondary bacterial/fungal infections).*
Unknown: Edema
Common: Blood bilirubin increased, Aspartate aminotransferase increased, Alanine aminotransferase increased
Unknown: Blood pressure decreased, Blood creatinine increased, Hepatic enzyme increased
* Incidence of paradoxical drug reaction: Lower frequency is reported as 9.2% (53/573) (data between October 2007 and March 2010) and higher frequency is reported as 25% (19/76) (data between 2000 and 2010).
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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