ISONIAZID

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Isoniazid is an antibiotic used to prevent and treat tuberculosis. To prevent development of resistant tuberculosis bacteria, people with tuberculosis are treated with long courses of combination drug therapy, most commonly isoniazid, rifampin, and pyrazinamide.

Safetychecker Summary for Isoniazid
(for details about the summarized interactions, read the full article)

May be Beneficial: Depletion or interference—The medication may deplete or interfere with the absorption or function of the nutrient. Taking these nutrients may help replenish them.	Calcium* Folic acid* Magnesium* Vitamin B12 Vitamin B3 Vitamin B6 Vitamin D* Vitamin E* Vitamin K
May be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication.	Picrorhiza*
May be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better.	Licorice*
Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	Vitamin B6
Reduced drug absorption/bioavailability	None known

Interactions with Dietary Supplements

Vitamin B3
Isoniazid is capable of causing vitamin B3 (niacin) deficiency, most likely due to its ability to interfere with cell-repair enzymes made from niacin. Significant niacin deficiency, also known as pellagra, features dermatitis, diarrhea, and dementia (impaired intellectual function). Supplementation with vitamin B6 is thought to reduce this risk, although small amounts (e.g. 10 mg daily) has been noted to be inadequate in some cases.¹

Vitamin B6
Isoniazid can interfere with the activity of vitamin B6.² Vitamin B6 supplementation is recommended, especially in people with poor nutritional status, to prevent development of isoniazid-induced peripheral neuritis (inflamed nerves).³ One case is reported in which injectable vitamin B6 reversed isoniazid-induced coma.⁴ In another case, however, 10 mg per day of vitamin B6 failed to reverse isoniazid-induced psychosis. The author suggested that higher amounts (e.g., 50 mg per day) may be needed.⁵ Although the optimal amount remains unknown, some doctors suggest that adults taking isoniazid supplement with 100 mg of vitamin B6 per day to prevent side effects. However, animal studies suggest that administration of very large amounts of vitamin B6 can interfere with the effect of isoniazid.⁶

Vitamin K
Many antibiotics taken by mouth, including isoniazid, may kill friendly bacteria in the large intestine that produce vitamin K.⁷ Vitamin K1 (phylloquinone) is now found in some multivitamins.

Other nutrient interactions
Isoniazid may interfere with the activity of other nutrients, including vitamin B3 (niacin), vitamin B12, vitamin D, and vitamin E, folic acid, calcium, and magnesium.^{8 9} Supplementation with vitamin B6 is thought to help prevent isoniazid-induced niacin deficiency; however, small amounts of vitamin B6 (e.g. 10 mg per day) appear to be inadequate in some cases.¹⁰ People should consider using a daily multivitamin-mineral supplement during isoniazid therapy.

Interactions with Herbs

Licorice (Glycyrrhiza glabra)
The potent anti-inflammatory substance known as glycyrrhizin from licorice has been combined with isoniazid for treatment of tuberculosis. An older study found a benefit from combining the two compared to using isoniazid alone.¹¹ Glycyrrhizin was given by injection, so it is not certain if licorice extracts containing glycyrrhizin would be as effective given by mouth. The treatment required at least three months of administration.

Picrorhiza (Picrorhiza kurroa)
Picrorhiza is an herb from India with well-established anti-inflammatory and liver protective actions.¹² Use of a combination formula known as Liv.100 that contains picrorhiza protected animal livers against damage caused by isoniazid and other antituberculosis antibiotics.¹³

Interactions with Foods and Other Compounds

Food
Food decreases absorption of isoniazid. Isoniazid should be taken one hour before or two hours after eating. However, people may take isoniazid with food to decrease stomach upset.¹⁴

Isoniazid has some monoamine oxidase inhibitor (MAOI) activity.¹⁵ Isoniazid can alter metabolism of tyramine-containing foods, leading to reactions associated with MAOI drugs (diarrhea, flushing, sweating, pounding chest, dangerous changes in blood pressure, and other symptoms).¹⁶ People taking isoniazid should avoid tyramine-containing foods. Isoniazid can also alter metabolism of histamine-containing foods, leading to headaches, sweating, pounding chest, flushing, diarrhea, low blood pressure, and itching.¹⁷ People taking isoniazid should avoid histamine-containing foods (such as tuna, sauerkraut juice, or yeast extract).

Alcohol
Daily alcohol intake increases the risk of isoniazid-related hepatitis.¹⁸ Alcohol may interact with isoniazid, causing facial flushing, headache, light-headedness, nausea, breathlessness, and other symptoms.¹⁹ To prevent unwanted reactions, people taking isoniazid should avoid alcohol-containing products.

1. Darvay A, Basarab T, McGregor JM, Russell-Jones R. Isoniazid induced pellagra despite pyridoxine supplementation. Clin Exp Dermatol 1999;24:167–70.

2. Goldman AL, Braman SS. Isoniazid: a review with emphasis on adverse effects. Chest 1972;62:71–7 [review].

3. Mandell GL, Petri WA Jr . Antimicrobial Agents: Drugs used in the chemotherapy of tuberculosis, Mycobacterium avium complex disease and leprosy. In Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw-Hill, 1996, 1158.

4. Brent J, Vo N, Kulig K, Rumack BH. Reversal of prolonged isoniazid-induced coma by pyridoxine. Arch Intern Med 1990;150:1751–3.

5. Chan TYK. Pyridoxine ineffective in isoniazid-induced psychosis. Ann Pharmacother 1999;33:1123–4 [letter].

6. McCune R, Deuschle K, McDermott W. The delayed appearance of isoniazid antagonism by pyridoxine in vivo. Am Rev Tuberculosis 1957;76:1100–5.

7. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 147.

8. Werbach MR. Foundations of Nutritional Medicine. Tarzana, CA: Third Line Press, 1997, 231–2 [review].

9. Holt GA. Food & Drug Interactions. Chicago, Precept Press, 1998, 146–7.

10. Darvay A, Basarab T, McGregor JM, Russell-Jones R. Isoniazid induced pellegra despite pyridoxine supplementation. Clin Exp Dermatol 1999;24:167–9.

11. Aoki K, Tokiwa T, Yamamoto T, Teramatsu T. Combined treatment of pulmonary tuberculosis with glycyrrhizin and INH. Acta Tubercul Japon 1963;13:32–9.

12. Floersheim GL, Bieri A, Koenig R, Pletscher A. Protection against Amanita phalloides by the iridoid glycoside mixture of Picrorhiza kurroa (kutkin). Agents Actions 1990;29:386–7.

13. Saraswathy SD, Shyamala Devi CS. Hepatoprotective effect of Liv.100, a polyherbal formulation, on mitochondrial enzymes in anti-tubercular drug-induced liver damage in rats. J Clin Biochem Nutr 1999;26:27–34.

14. Threlkeld DS, ed. Systemic Anti-Infectives, Antituberculosis Drugs, Isoniazid. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1990, 382–5.

15. Threlkeld DS, ed. Systemic Anti-Infectives, Antituberculosis Drugs, Isoniazid. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1990, 382–5.

16. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 146.

17. Threlkeld DS, ed. Systemic Anti-Infectives, Antituberculosis Drugs, Isoniazid. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1990, 382–5.

18. Threlkeld DS, ed. Systemic Anti-Infectives, Antituberculosis Drugs, Isoniazid. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1990, 382–5.

19. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 144.

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Copyright © 2002 Healthnotes, Inc.  All rights reserved. www.healthnotes.com

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2003.

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