Rifampicin: Rifampicin is not recommended for intermittent therapy; the patient should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases. Rifampicin has been observed to increase the requirements for anticoagulant drugs of the coumarin type. The cause of the phenomenon is unknown. In patients receiving anticoagulants and rifampicin concurrently, it is recommended that the prothrombin time be performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant. Urine, feces, saliva, sputum, sweat and tears may be colored red-orange by rifampicin and its metabolites. Soft contact lenses may be permanently stained. Individuals to be treated should be made aware of these possibilities.
It has been reported that the reliability of oral contraceptives may be affected in some patients being treated for tuberculosis with rifampicin in combination with at least 1 other antituberculosis drug. In such cases, alternative contraceptive measures may need to be considered. It has also been reported that rifampicin given in combination with other antituberculosis drugs may decrease the pharmacologic activity of methasone, oral hypoglycemics, digitoxin, quinidine, disopyramide, dapsone and corticosteroids. In these cases, dosage adjustment of the interacting drugs is recommended.
Therapeutic levels of rifampicin have been shown to inhibit standard microbiological assays for serum folate and vitamin B12. Alternative methods must be considered when determining folate and vitamin B12 concentrations in the presence of rifampicin.
Isoniazid: All drugs should be stopped and an evaluation of the patient should be made at the first sign of a hypersensitivity reaction. Use of isoniazid should be carefully monitored in the following: Patients who are receiving phenytoin (diphenylhydantoin) concurrently. Isoniazid may decrease the excretion of phenytoin or may enhance its effects. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant dose should be made; daily users and ingestion of alcohol may be associated with a higher incidence of isoniazid-hepatitis; patient with current chronic liver disease or severe renal dysfunction. Periodic ophthalmoscopic examination during isoniazid therapy is recommended when visual symptoms occur.
Ethambutol: The effects of combinations of ethambutol with other antituberculous drugs on the fetus is not known. Patients with decreased renal function need the dosage reduced as determined by serum levels of ethambutol, since the main path of excretion of this drug is by the kidneys. Because ethambutol may have adverse effects on vision, physical examination should include ophthalmoscopy, finger perimetry and testing of color discrimination. In patients with visual defects eg, cataracts recurrent inflammatory conditions of the eye, optic neuritis and diabetic retinopathy, the evaluation of changes in visual acuity is more difficult and care should be taken to be sure the variations in vision are not due to the underlying disease conditions. In such patients expected and possible visual deterioration since evaluation of visual changes is difficult. As with any potent drug, periodic assessment of organ system functions, including renal, hepatic and hematopoietic should be made during long-term therapy.
Pyrazinamide: Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia which is usually asymptomatic. Pyrazinamide also causes hyperuricemia which is accompanied by acute gouty arthritis.
Use in pregnancy & lactation: Rifampicin: Since rifampicin has been reported to cross the placental barrier and appear in cord blood and in maternal milk, neonates and newborns of rifampicin-treated mothers should be carefully observed for any evidence of untoward effects.
Ethambutol: While administration of ethambutol to pregnant human patients has produced no detectable effect upon the fetus, the possible teratogenic potential in women capable of bearing children would be weighed carefully against the benefits of therapy. There are published reports of 5 women who received ethambutol during pregnancy without apparent adverse effect upon the fetus.
Use in children: Ethambutol is not recommended for use in children <13 years since safe conditions for use have not been established.