Drug Interaction:
Interacting drugs- summary
Rifampicin + Isoniazid + Pyrazinamide +
Paracetamol
Paracetamol levels are increased by INH leading to liver toxicity
Antacids
Antacids reduce absorption of rifampicin, INH.
Pyrazinamide
Pyrazinamide reduces uricosuric action of probenicid if given after the drug.
If given before the drug, alters uricosuric action and half-life prolonged.
Rifampicin induces while INH inhibits liver enzymes.
Vitamin D3
Rifampicin+ INH reduce levels of 125 dihydroxy Vitamin D3.
Oral contraceptives
Failure of oral contraceptives,
Phenytoin
Decreased excretion of phenytoin.
Methadone/ Digoxin / Steroids
Decreased pharmacological activity of methadone,oral hypoglycaemics,
digoxin, quinidine and steroids.
Adverse Reaction:
Liver damage, hyperuricaemia, Acute gout, arthalgia, arthritis, Neuropathies, convulsions, Cutaneous syndrome, Flushing,itching and rash.
Hypersensitivity to isoniazid -skin rash, fever, Lymphadenopathy, vasculitis, rarely SLE. Flu like syndrome with rifampicin during intermittant theapy. Photosensitisation and GI upsets with pyrazinamide.
Contra-Indications:
Rifampicin, isoniazid, pyrazinamide
Contraindicated in patients with history of hypersensitivity to rifampicin, isoniazid, pyrazinamide ethambutol.
Contraindicated in patients with severe hepatic damage, severe adverse reactions to isoniazid (fever, chills and arthiritis) acute liver disease of any origin, acute gout.
Ethambutol
Etambutol is contraindicated in patients with optic neuritis
Pyridoxine
Contraindicated in patients with sensitivity to pyridoxine
Special precautions:
Rifampicin, isoniazid, pyrazinamide
Rifampicin can cause liver damage.
Severe sometimes fatal hepatitis associated with isoniazid/pyrazinamide therapy has also been observed. Hence, prior to and during therapy, patients with impaired liver function should be subjected to evaluation of serum glutamic pyruvic transaminase (SGOT)
If hyperurecemia, accompanied by an acute gouty arthritis occurs without liver dysfunction,
then it is advisable to transfer the patients to a regimen not containing pyrazinamide.
Rifampicin to be avoided in patients with acute porphyria
Dosages/ Overdosage Etc:
Tuberculosis
Dosage-
2 tabs daily as a single dose either 1 hour before or 2 hours after meals
Patient Information:
1. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to rifampicin, isoniazid or pyrazinamide. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.
2.Pregnancy - pregnant women with tuberculosis should be treated with TB medicines including rifampicin, isoniazid and pyrazinamide. Rifampicin , isoniazid and pyrazinamide combination has not been shown to cause birth defects or other problems.
3.Breast feeding- rifampicin, isoniazid and pyrazinamide pass into the breast milk. However it has not been reported cause problems in nursing babies
4.Children- this combinaton may not be appropriate for use in children.
5. Elderly- liver problems are more likely to occur in patients over 50 years of age.
6. Other medicines - Acetoaminophen or Amiodarone or Anabolic stroids or Androgens or Antithyroid agents or Carbamazepine or Carmustine or Chloroquine or Dantrolene or Daunorubicin or Dissulfram or Divalproex or Etretinate or Gold salts or Hydroxychloroquine Mercaptopurine or Methyldopa or Naltrexone or Other anti-infectives by mouth or Phenothiazines or Pilcamycin or Valproic acid - these medicines may increase the chance of liver damage if taken with this combination Anticoagulants or Aminophylline or Antidiabetics or Chloramphenicol or Corticosteroids or Digitalis glycosides or Disopyramide or Estrmustine or Fluconazole or Itraconazole or Ketoconazole or Methadone or Methotrexate or Mexilitine or Oxytriphylline or Qunidine or Theophylline or Tocainide or Verapramil - this combination may decrease the effects of these medicines Disulfram or - this medicine may increase the chance of liver damage Estrogens or Oral contraceptives or Phenytoin - this combinatiuon may decrease the effects of these medicines.
If you are taking oral contraceptives this may increase the chance of pregnancy. May also increase the chance of liver damage if taken with this combinatiuon.
10. Other medical problems - Tell your doctor if you have any other medical problems especially - Alcohol abuse or Liver disease - there may be an increased chance of getting hepatitis if you take this medicine and drink alcohol daily. Convulsive disorders- may increase the frequency of convulsions Gout - this combination may worsen the goiout attack. Kidney disease- increased chance of side efects.
11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.
13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Pharmacokinetics:
An open cross over study was conducted on healthy subjects with normal liver and kidney function, to evaluate the pharmacokinetic profile of rifampicin, isoniazid, and pyrazinamide, given as a combination. They were treated free and fixed triple dose combination at interval of one week. The pharmacokinetic properties were compared based on blood concentration up to 12 hrs with proportions of the dose of the drugs and their metabolites in the urine. No negative pharmacokinetic interaction could be observed in either situation. The results of these studies show the pharmacokinetic proifiles of rifampicin, isoniazid,and pyrazinamide assessed individually and in fixed triple dose are comparable.
Interaction with Food:
Food reduces the absorption of isoniazid.
Manufacturer Details