Rifampicin and Isoniazid interacts in the following cases:
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 glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 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 If signs of hepatocellular damage occur, rifampicin should be withdrawn.
Rifampicin should also be withdrawn if clinically significant changes in hepatic function occur.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.
Use of isoniazid should be carefully monitored in patients with current chronic liver disease or severe renal dysfunction.
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.
Para-aminosalicylic acid may increase the plasma concentration and elimination half-life of isoniazid by competing for acetylating enzymes.
Rifampicin has been shown to be teratogenic in rodents when given in large doses. There are no well controlled studies with rifampicin/isoniazid combination 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.
When administered during the last few weeks of pregnancy, rifampicin can cause post-natal haemorrhages in the mother and infant, for which treatment with Vitamin K1 may be indicated.
It has been reported that in both rats and rabbits, isoniazid may exert an embryocardial effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species (mice, rats, rabbits).
Therefore, rifampicin/isoniazid combination 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.
Rifampicin and isoniazid are excreted in breast milk and infants should not be breast fed by a patient receiving rifampicin/isoniazid combination unless in the physician’s judgement the potential benefit to the patient outweighs the potential risk to the infant.
In breast-fed infants whose mothers are taking isoniazid, there is a theoretical risk of convulsions and neuropathy (associated with vitamin B6 deficiency), therefore they should be monitored for early signs of these effects and consideration should be given to treating both mother and infant prophylactically with pyridoxine.
Isoniazid has been associated with vertigo, visual disorders and psychotic reactions. Patients should be informed of these, and advised that if affected, they should not drive, operate machinery or take part in any activities where these symptoms may put either themselves or others at risk.
The following CIOMS frequency rating is used, when applicable: Very common (≥1/10); Common (≥1/100 to <1/ 10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000), not known (cannot be estimated from available data).
Reactions to rifampicin occurring with either daily or intermittent dosage regimens include:
| System organ class | Frequency | Preferred Term |
|---|---|---|
| Infections and infestations | Unknown | Pseudomembranous colitis Influenza |
| Blood and lymphatic system disorders | 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 | |
| Immune system disorders | Unknown | Anaphylactic reaction |
| Endocrine disorders | Unknown | Adrenal insufficiency in patients with compromised adrenal function have been observed |
| Metabolism and nutritional disorders | Unknown | Decreased appetite |
| Psychiatric disorders | Unknown | Psychotic disorder |
| Nervous system disorders | Common | Headache Dizziness |
| Unknown | Cerebral hemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura | |
| Eye disorders | Unknown | Tear discolouration |
| Vascular disorders | Unknown | Shock Flushing Vasculitis Bleeding |
| Respiratory, thoracic and mediastinal disorders | Unknown | Dyspnoea Wheezing Sputum discoloured |
| Gastrointestinal disorders | Common | Nausea Vomiting |
| Uncommon | Diarrhea | |
| Unknown | Gastrointestinal disorder Abdominal discomfort Tooth discolouration (which may be permanent) | |
| Hepatobiliary disorders | Unknown | Hepatitis Hyperbilirubinaemia |
| Skin and subcutaneous tissue disorders | 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 |
| Musculoskeletal and connective tissue disorders | Unknown | Muscle weakness Myopathy Bone pain |
| Renal and urinary disorders | Unknown | Acute kidney injury usually due to renal tubular necrosis or tubulointerstitial nephritis Chromaturia |
| Pregnancy, puerperium and perinatal conditions | Unknown | Post-partum haemorrhage Fetal-maternal haemorrhage |
| Reproductive system and breast disorders | Unknown | Menstrual disorder |
| Congenital, familial and genetic disorders | Unknown | Porphyria |
| General disorders and administration site conditions | 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 anti-tuberculosis 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 | |
| Investigations | 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).
| System organ class | Frequency | Preferred Term |
|---|---|---|
| Nervous system disorders | Uncommon | Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis. |
| Not known | Vertigo Polyneuritis, presenting as paresthesia, muscle weakness, loss of tendon reflexes, etc, is unlikely to occur with the recommended daily dose of rifampicin/isoniazid. The incidence is higher in “slow acetylators”. The possibility that the frequency of seizures may be increased in patients with epilepsy should be borne in mind. | |
| Skin and Subcutaneous tissue disorders | Not known | Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome Rash Acne Toxic Epidermal Necrolysis (TEN) Stevens-Johnson syndrome Exfoliative dermatitis Pemphigus |
| Vascular disorders | Not known | Vasculitis |
| Blood and lymphatic system disorders | Not known | Eosinophilia Agranulocytosis Thrombocytopenia Anemia Aplastic anaemia Haemolytic anaemia |
| Gastrointestinal disorders | Not known | Constipation Dry mouth Nausea Vomiting Epigastric distress Pancreatitis |
| Hepatobiliary disorders | Uncommon | Severe and sometimes fatal hepatitis may occur with isoniazid therapy |
| Endocrine disorders | Not known | Gynaecomastia |
| Investigations | Not known | Anti-nuclear bodies |
| Metabolism and nutrition disorders | Not known | Hyperglycaemia Pellagra |
| Musculoskeletal and connective tissue disorders | Not known | Systemic lupus erythematous-like syndrome |
| General disorders and administration site conditions | Not known | Fever |
| Immune system disorders | Not known | Anaphylactic reactions |
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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