Isoniazid + Vitamin B6

Usage

Isoniazid + Vitamin B6 is primarily prescribed for the treatment and prevention of tuberculosis (TB). It is a fixed-dose combination medication containing an antibiotic (isoniazid) and a vitamin (pyridoxine, Vitamin B6). Isoniazid is bactericidal against actively growing Mycobacterium tuberculosis. Vitamin B6 is added to mitigate the risk of peripheral neuropathy, a common side effect of isoniazid.

• Pharmacological Classification: Antibiotic (specifically, an antimycobacterial), fixed-dose combination with a vitamin supplement.

• Mechanism of Action: Isoniazid acts as a prodrug, activated by the mycobacterial catalase-peroxidase enzyme KatG. This activation leads to the formation of reactive species that inhibit mycolic acid synthesis, a critical component of the mycobacterial cell wall. This disruption of cell wall synthesis results in bacterial death.

Alternate Names

• International/Regional Variations: Isoniazida (Spanish), Isoniazidum (Latin)
• Brand Names: Nydrazid (often combined with other anti-TB drugs in branded formulations)

How It Works

• Pharmacodynamics: Isoniazid exerts its bactericidal effect specifically on Mycobacterium tuberculosis by inhibiting mycolic acid synthesis. It is effective against both intracellular and extracellular organisms. Pyridoxine (Vitamin B6) helps prevent isoniazid-induced peripheral neuropathy by acting as a cofactor for enzymes involved in neurotransmitter synthesis.

• Pharmacokinetics: Isoniazid is well-absorbed orally and distributed widely throughout the body, including the cerebrospinal fluid (CSF). It is metabolized primarily in the liver by acetylation (via N-acetyltransferase 2, NAT2) and is excreted primarily in the urine. The rate of acetylation is genetically determined, resulting in “fast” and “slow” acetylators. This genetic polymorphism can affect the drug’s efficacy and toxicity profile. Vitamin B6 is also well-absorbed orally and is converted to its active form, pyridoxal 5’-phosphate. It is excreted in the urine.

• Mode of Action (Cellular/Molecular): Isoniazid targets InhA, an enoyl-acyl carrier protein reductase involved in mycolic acid synthesis. By inhibiting InhA, isoniazid disrupts the formation of the mycobacterial cell wall, leading to cell death.

• Elimination Pathways: Primarily renal excretion of metabolites following hepatic acetylation.

Dosage

Standard Dosage

Adults:

• Latent TB Infection (LTBI): 300 mg orally once daily for 9 months or 900 mg plus rifapentine 900 mg orally once weekly for 3 months (for patients ≥12 years).
• Active TB Disease: 5 mg/kg (up to 300 mg) orally once daily or 15 mg/kg (up to 900 mg) two or three times weekly.

Children:

• LTBI: 10 mg/kg (up to 300 mg) orally once daily for 9 months.
• Active TB Disease: 10-20 mg/kg (up to 300 mg) orally once daily or 20-40 mg/kg (up to 900 mg) two or three times weekly.

Special Cases:

• Elderly Patients: Dosage adjustment may be needed based on renal and hepatic function. Close monitoring for hepatotoxicity is recommended.

• Patients with Renal Impairment: Dosage adjustment may be required for severe renal impairment.

• Patients with Hepatic Dysfunction: Caution is advised. Dose reduction or discontinuation may be necessary depending on the severity of impairment. Close monitoring for hepatotoxicity is essential.

• Patients with Comorbid Conditions: Consider potential drug interactions, particularly with diabetes, HIV, or malnutrition (increased risk of neuropathy) and alcohol dependence (increased risk of both neuropathy and hepatotoxicity).

Clinical Use Cases

The provided sources do not specifically mention isoniazid + Vitamin B6 for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its use is primarily focused on TB treatment and prevention.

Dosage Adjustments

Dose adjustments should be made based on patient-specific factors like renal or hepatic dysfunction, age, and comorbid conditions as mentioned above. Genetic polymorphisms affecting NAT2 activity should also be considered, as slow acetylators may require lower doses to avoid toxicity.

Side Effects

Common Side Effects:

• Peripheral neuropathy (numbness, tingling, burning in hands and feet)
• Nausea, vomiting
• Loss of appetite
• Mild elevation of liver enzymes

Rare but Serious Side Effects:

• Severe hepatitis (liver damage)
• Seizures
• Drug-induced lupus
• Sideroblastic anemia

Long-Term Effects:

Chronic liver disease (with prolonged use, especially in patients with pre-existing liver conditions or alcohol abuse).

Adverse Drug Reactions (ADR):

Hepatitis, seizures, severe skin reactions (e.g., Stevens-Johnson syndrome), agranulocytosis.

Contraindications

• Hypersensitivity to isoniazid
• Previous isoniazid-induced hepatitis
• Acute liver disease

Drug Interactions

Isoniazid interacts with numerous medications, including:

• Anticonvulsants (e.g., phenytoin): Increased risk of phenytoin toxicity.
• Aluminum-containing antacids: Reduced isoniazid absorption.
• Disulfiram: Increased risk of neurotoxicity.
• Ketoconazole: Increased risk of isoniazid toxicity.
• Rifampin: Increased risk of hepatotoxicity.

Also, consider interactions with alcohol (increased risk of neuropathy and hepatotoxicity), tyramine-containing foods, and certain other anti-TB drugs.

Pregnancy and Breastfeeding

• Pregnancy: Isoniazid is generally considered safe during pregnancy, but should only be used if the benefits outweigh the risks. Pyridoxine supplementation is recommended. The 3-month regimen with rifapentine is not recommended during pregnancy.

• Breastfeeding: Isoniazid is excreted in breast milk. Breastfeeding is generally considered safe while taking isoniazid, but infants should be monitored for potential side effects (especially jaundice). Pyridoxine supplementation is recommended for breastfeeding mothers taking isoniazid.

Drug Profile Summary

• Mechanism of Action: Inhibits mycolic acid synthesis, disrupting mycobacterial cell wall formation.

• Side Effects: Peripheral neuropathy, nausea, vomiting, hepatotoxicity (rare but serious).

• Contraindications: Isoniazid hypersensitivity, previous isoniazid-induced hepatitis, acute liver disease.

• Drug Interactions: Numerous drug interactions, including with anticonvulsants, antacids, and rifampin.

• Pregnancy & Breastfeeding: Generally safe with pyridoxine supplementation; monitor infant.

• Dosage: LTBI: Adults: 300 mg/day for 9 months. Active TB: Adults: 5 mg/kg/day. Pediatric dosages vary by age and weight.

• Monitoring Parameters: Liver function tests (LFTs) at baseline and periodically during treatment, signs and symptoms of peripheral neuropathy.

Popular Combinations

Isoniazid is often used in combination with other anti-TB drugs, such as rifampin, pyrazinamide, and ethambutol, to enhance efficacy and prevent the development of drug resistance.

Precautions

• General Precautions: Obtain baseline LFTs, monitor for signs of hepatotoxicity and peripheral neuropathy, assess alcohol consumption, and consider drug interactions.

• Specific Populations: As detailed above.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Isoniazid + Vitamin B6?

A: The dosage varies depending on whether it is used for LTBI or active TB, as well as the patient’s age and weight. Refer to the detailed dosage guidelines provided earlier.

Q2: What is the role of Vitamin B6 in this combination?

A: Vitamin B6 (pyridoxine) is included to prevent or mitigate peripheral neuropathy, a common side effect of isoniazid.

Q3: What are the most serious side effects of isoniazid?

A: The most serious side effect is hepatotoxicity (liver damage), which can be fatal. Patients should be monitored closely for signs and symptoms of hepatitis.

Q4: Can Isoniazid + Vitamin B6 be used during pregnancy?

A: Yes, isoniazid is generally considered safe during pregnancy, but it should only be used if the benefits outweigh the risks. Pyridoxine supplementation is crucial. The 3-month regimen with rifapentine is contraindicated.

Q5: Can Isoniazid + Vitamin B6 be used during breastfeeding?

A: Yes, isoniazid does transfer into breast milk, but breastfeeding is generally considered safe. Infants should be monitored for potential adverse effects, and pyridoxine supplementation is recommended for the mother.

Q6: What are the signs and symptoms of peripheral neuropathy?

A: Numbness, tingling, burning, or pain in the hands and feet are the most common symptoms.

Q7: How is isoniazid metabolized?

A: Isoniazid is metabolized in the liver primarily through acetylation by the NAT2 enzyme. Genetic variations in NAT2 activity can result in “fast” or “slow” acetylator phenotypes.

Q8: What should I do if a patient develops signs of hepatotoxicity while on isoniazid?

A: Discontinue isoniazid immediately and consult a specialist. Liver function tests should be monitored closely.

Q9: Why is isoniazid often combined with other TB drugs?

A: Combining isoniazid with other anti-TB medications is essential to enhance treatment efficacy and prevent the emergence of drug-resistant strains of Mycobacterium tuberculosis.

Q10: How should I counsel patients about alcohol consumption while on isoniazid?

A: Patients should be advised to limit or avoid alcohol consumption while taking isoniazid due to the increased risk of peripheral neuropathy and hepatotoxicity.