Rifampicin / Isoniazid

MODE OF ACTION

Rifampicin inhibits the DNA-dependent RNA polymerase of sensitive bacterial strains, but without affecting the host enzymatic systems.

Isoniazid exerts a bactericidal effect mainly on rapidly growing populations of Mycobacterium tuberculosis. Its mechanism of action is probably based chiefly on inhibition of mycolic acid synthesis, mycolic acid being an important constituent of the mycobacterial cell wall.

Drug Label Information | Brands:

Brands Available in Kenya

Akurit®, Lupin
Akurit Z Kid®, Lupin
Macox Plus®, Macleods
R-cinex®, Lupin
RH Com® , Macleods Pharmaceuticals Limited
Rifampicin / Isoniazid , Svizera Labs Private Limited
Rifampicin / Isoniazid , Macleods Pharmaceuticals Limited
Rifisal®, Universal Corporation
Rifinah®, Sanofi-aventis Kenya
Rihaz® , Cosmos Limited
Rihide®, Cosmos Limited
Rihide-P®, Cosmos Limited
Rimactazid® , Sandoz Private Limited

INDICATIONS:

This Combination is indicated in the treatment of all forms of tuberculosis, including fresh, advanced and chronic cases.

CONTRAINDICATIONS:

This combination is contraindicated in:

  • patients who are hypersensitive to rifamycins or isoniazid or any of the excipients
  • the presence of jaundice;
  • concurrent treatment with the combination of saquinavir/ritonavir

ADVERSE DRUG REACTIONS:

Undiserable Effects of Rifampicin:

Infections and infestations
Pseudomembranous colitis
Influenza

Blood and lymphatic system disorders
Thrombocytopenia with or without purpura, usually associated with intermittent therapy, but is reversible if drug is discontinued as soon as purpura occurs.

Immune system disorders
Anaphylactic reaction

Endocrine disorders
Adrenal insufficiency in patients with compromised adrenal function have been observed

Metabolism and nutritional disorders
Decreased appetite

Psychiatric disorders
Psychotic disorder

Nervous system disorders
Headache
Dizziness

Eye disorders
Tear discolouration

Vascular disorders
Shock
Flushing
Vasculitis
Bleeding

Respiratory, thoracic and mediastinal disorders
Dyspnoea
Wheezing
Sputum discoloured

Gastrointestinal disorders
Nausea
Vomiting
Diarrhea

Hepatobiliary disorders
Hepatitis
Hyperbilirubinaemia

Skin and subcutaneous tissue disorders
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
Muscle weakness
Myopathy
Bone pain

Renal and urinary disorders
Acute kidney injury usually due to renal tubular necrosis or tubulointerstitial nephritis
Chromaturia

Pregnancy, puerperium and perinatal conditions
Post-partum haemorrhage
Fetal-maternal haemorrhage

Reproductive system and breast disorders
Menstrual disorder

Congenital, familial and genetic disorders
Porphyria

General disorders and administration site conditions
Pyrexia
Chills

Investigations
Blood bilirubin increased
Aspartate aminotransferase increased
Alanine aminotransferase increased

Undesirable effects of isoniazid

Blood and lymphatic system disorders:
Rare: Eosinophilia, thrombocytopenia, anaemia (haemolytic, sideroblastic)

Endocrine disorders:
Rare: soniazid may interfere with liver metabolism of several hormones, resulting in menstrual disturbances, gynaecomastia, Cushing syndrome, pubertas praecox, and difficult controllable diabetes, hyperglycaemia

Psychiatric disorders:
Rare: Psychoses, hyperactivity, euphoria, insomnia

Nervous system disorders
Common: Peripheral neuropathy (dose dependent and more common in undernourished patients, alcoholics, slow acetylators and diabetics), usually preceded by paresthesias of feet and hands
Rare: Damage to the optic nerve (see section 4.4), convulsions, dizziness, light-headedness, headache, toxic encephalopathy. High doses may increase seizure frequency in epileptics

DRUG INTERACTIONS:

Rifampicin

The potential for hepatotoxicity is increased with an anaesthetic.

When rifampicin is given concomitantly with either halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampicin and halothane should be avoided.

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 (specially with high doses).

Examples of drugs or drug classes affected by Rifinah:

  • Antiarrhythmics (e.g. disopyramide, mexiletine, quinidine, propafenone, tocainide),
  • Antiepileptics (e.g. phenytoin),
  • Hormone antagonist (antiestrogens e.g. tamoxifen, toremifene, gestinone),
  • Antipsychotics (e.g. haloperidol, aripiprazole),
  • Anticoagulants (e.g. coumarins),
  • Antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole),
  • Antivirals (e.g. saquinavir, indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir, nevirapine),
  • Barbiturates,
  • Beta-blockers (e.g. bisoprolol, propanolol),
  • Anxiolytics and hypnotics (e.g. diazepam, benzodiazepines, zopiclone, zolpidem),
  • Calcium channel blockers (e.g. diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisoldipine),
  • Antibacterials (e.g. chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, telithromycin
  • Corticosteroids,
  • Cardiac glycosides (e.g. digitoxin, digoxin),
  • Clofibrate,
  • Systemic hormonal contraceptives including estrogens and progestogens,
  • Antidiabetic (e.g. chlorpropamide, tolbutamide, sulfonylureas, rosiglitazone),
  • Immunosuppressive agents (e.g. ciclosporin, sirolimus, tacrolimus)
  • Irinotecan,
  • Thyroid hormone (e.g. levothyroxine),
  • Losartan,
  • Analgesics (e.g. methadone, narcotic analgesics),
  • Praziquantel,
  • Quinine,
  • Riluzole,
  • Selective 5-HT3 receptor antagonists (e.g. ondansetron)
  • Statins metabolised by CYP 3A4 (e.g. simvastatin),
  • Theophylline,
  • Tricyclic antidepressants (e.g. amitriptyline, nortriptyline),
  • Cytotoxics (e.g. imatinib),
  • Diuretics (e.g. eplerenone).
  • Enalapril: decrease enalapril active metabolite exposure. Dosage adjustments should be made if indicated by the patient’s clinical condition

Hepatitis-C antiviral drugs (eg. daclatasvir, simeprevir, sofosbuvir, telaprevir): Concurrent use of treatment of hepatitis-C antiviral drugs and rifampicin should be avoided.

Morphine: 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 with rifampicin.

Rifampicin treatment reduces the systemic exposure of oral contraceptives. Patients using oral contraceptives should be advised to change to non-hormonal methods of birth control during Rifinah therapy. Also, diabetes may become more difficult to control.

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.

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.

When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.

Isoniazid

The following drugs may interact with isoniazid:

Antiepileptics (e.g. carbamazepine and phenytoin).

There may be an increased risk of distal sensory neuropathy when isoniazid is used in patients taking stavudine.

Concomitant use of zalcitabine with isoniazid has been shown to approximately double the renal clearance if isoniazid in HIV infected patients.

Para-aminosalicylic acid may increase the plasma concentration and elimination half-life of isoniazid by competing for acetylating enzymes.

General anaesthetics may increase the hepatotoxicity of isoniazid.

The absorption of isoniazid is reduced by antacids.

The risk of CNS toxicity is increased when isoniazid is given with cycloserine.

Isoniazid may reduce plasma concentration of ketoconazole and increase plasma concentration of theophylline.