Usage
This combination drug is primarily prescribed for the treatment of active tuberculosis (TB). It is also used for the prevention of TB in individuals who have been exposed to the bacteria or are at high risk of developing the disease (latent TB infection).
Pharmacological Classification: Antimycobacterial, Antituberculosis
Mechanism of Action: This combination targets Mycobacterium tuberculosis through multiple pathways. Isoniazid inhibits mycolic acid synthesis, a crucial component of the bacterial cell wall. Rifampicin inhibits bacterial RNA polymerase, thus suppressing gene transcription. Vitamin B6 (pyridoxine) is included to mitigate the peripheral neuropathy, a common side effect of isoniazid.
Alternate Names
This specific combination doesn’t have a universally recognized international nonproprietary name (INN). It’s often referred to as “isoniazid/rifampicin/pyridoxine” or “INH/RIF/B6”. Brand names vary depending on the manufacturer and region.
How It Works
Pharmacodynamics: Isoniazid is bactericidal against actively growing M. tuberculosis. Rifampicin is bactericidal against both intracellular and extracellular M. tuberculosis. Vitamin B6 doesn’t have a direct effect on the bacteria but protects against isoniazid-induced neuropathy by aiding in the synthesis of neurotransmitters.
Pharmacokinetics:
- Isoniazid: Well-absorbed orally. Metabolized in the liver by acetylation. Eliminated primarily through renal excretion.
- Rifampicin: Well-absorbed orally. Metabolized in the liver. Eliminated through biliary and renal pathways. Induces CYP450 enzymes, impacting the metabolism of other drugs.
- Vitamin B6: Readily absorbed from the GI tract. Excreted in urine.
Mode of Action: Isoniazid inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall. Rifampicin binds to the bacterial DNA-dependent RNA polymerase, blocking RNA synthesis.
Elimination Pathways:
- Isoniazid: Renal excretion (as metabolites).
- Rifampicin: Hepatic and biliary excretion, some renal excretion.
- Vitamin B6: Renal excretion.
Dosage
Standard Dosage
Adults:
For active TB:
- Isoniazid: 5 mg/kg (up to 300 mg) orally once daily or 15 mg/kg (up to 900 mg) two or three times weekly.
- Rifampicin: 10 mg/kg (up to 600 mg) orally once daily or 10mg/kg twice weekly DOT (not to exceed 600mg/day).
- Vitamin B6: 10-25 mg orally once daily.
For latent TB infection:
- Isoniazid: 300 mg orally once daily.
- Rifampicin: 600 mg orally once daily (in combination regimens for 3-4 months)
- Vitamin B6: 10-25 mg orally once daily.
Children:
Dosing for children should be determined by a pediatrician and is typically weight-based.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary based on renal and hepatic function.
- Patients with Renal Impairment: Dosage adjustments may be necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Close monitoring is required. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Individualized dosing considerations depending on the specific comorbidity.
Clinical Use Cases
Dosing for TB remains consistent across clinical settings. Specific regimens are determined by the type of TB (pulmonary, extrapulmonary, drug-resistant) and patient-specific factors.
Dosage Adjustments
Dosage adjustments should be made in cases of renal or hepatic impairment, and in patients with slow acetylator status (genetic polymorphism affecting isoniazid metabolism). Therapeutic drug monitoring may be beneficial in some cases.
Side Effects
Common Side Effects
- Nausea, vomiting
- Loss of appetite
- Abdominal discomfort
- Peripheral neuropathy (numbness, tingling in hands and feet)
- Orange discoloration of body fluids (urine, sweat, tears) with rifampicin
Rare but Serious Side Effects
- Drug-induced hepatitis
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Thrombocytopenia
- Acute renal failure
Long-Term Effects
Peripheral neuropathy can be a long-term effect of isoniazid if not managed appropriately. Hepatotoxicity may have long-term implications.
Adverse Drug Reactions (ADR)
Any signs of hepatitis (jaundice, dark urine, abdominal pain) or severe skin reactions warrant immediate discontinuation of the medication and medical attention.
Contraindications
- Hypersensitivity to any component of the drug.
- Acute liver disease.
- Porphyria.
- Chronic alcoholism.
Drug Interactions
Rifampicin is a potent inducer of CYP450 enzymes and can significantly decrease the effectiveness of many drugs, including:
- Antiretrovirals (e.g., protease inhibitors, non-nucleoside reverse transcriptase inhibitors)
- Oral contraceptives
- Warfarin
- Anticonvulsants
- Antifungals
Pregnancy and Breastfeeding
This drug combination can be used during pregnancy but requires careful monitoring. It is excreted in breast milk. The benefits of treatment for the mother often outweigh the risks to the fetus/infant, particularly in cases of active TB. Pyridoxine requirements are often increased in pregnancy.
Drug Profile Summary
- Mechanism of Action: Isoniazid inhibits mycolic acid synthesis, rifampicin inhibits RNA polymerase. Vitamin B6 prevents neuropathy.
- Side Effects: Nausea, vomiting, hepatitis, peripheral neuropathy, orange discoloration of body fluids (rifampicin).
- Contraindications: Hypersensitivity, acute liver disease, porphyria.
- Drug Interactions: Numerous, due to rifampicin’s effect on CYP450 enzymes.
- Pregnancy & Breastfeeding: Can be used with caution and monitoring.
- Dosage: See detailed section above.
- Monitoring Parameters: Liver function tests, signs of hepatitis, neurological examination for neuropathy.
Popular Combinations
The combination of isoniazid, rifampicin, pyrazinamide, and ethambutol is a standard first-line treatment for active TB.
Precautions
- Baseline liver function tests should be conducted and monitored regularly.
- Patients should be advised to report any signs or symptoms of hepatitis.
- Patients should be screened for risk factors of peripheral neuropathy (diabetes, alcoholism).
- Patients taking rifampicin should be educated about the potential for drug interactions and orange discoloration of body fluids.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Isoniazid + Rifampicin + Vitamin B6 in adults with active TB?
A: Isoniazid: 5 mg/kg (up to 300 mg) daily or 15 mg/kg (up to 900 mg) 2-3 times/week; Rifampicin: 10 mg/kg (up to 600 mg) daily or 10 mg/kg twice weekly DOT; Vitamin B6: 10-25 mg daily.
Q2: What is the role of Vitamin B6 in this combination?
A: It prevents peripheral neuropathy caused by isoniazid.
Q3: What are the most serious side effects to watch out for?
A: Hepatotoxicity (liver damage) and severe skin reactions.
Q4: Can this drug combination be used in pregnant women?
A: Yes, but with careful monitoring. Benefits often outweigh risks in active TB.
Q5: How does rifampicin affect other medications?
A: It induces CYP450 enzymes, reducing the efficacy of many drugs metabolized by this system.
Q6: What should patients be advised about rifampicin?
A: It can cause orange discoloration of body fluids (harmless but can stain contact lenses). Also, it interacts with many medications, including oral contraceptives.
Q7: How long is the treatment duration for active TB?
A: Typically 6-9 months, depending on the individual case and the specific regimen used.
Q8: What is the difference between active TB and latent TB infection?
A: Active TB is symptomatic and contagious. Latent TB infection is asymptomatic and not contagious.
Q9: What tests should be conducted before initiating treatment?
A: Liver function tests, renal function tests (if indicated), and possibly a chest X-ray.
Q10: What are the common drug interactions with isoniazid?
A: Isoniazid can interact with medications such as disulfiram, carbamazepine, phenytoin, and ketoconazole.
