Miracon Science

antituberculotics

Active substances and pharmaceuticals concerned

Name of active substance Trade name Affected micronutrients
Isoniazid  INH“Agepha“®, Rifoldin® Vitamin D
Vitamin A
Zinc
Rifampicin Rifoldin®
Pyrazinamide Pyrafat®
Ethambutol Etibi®

 

Specially affected active substances and pharmaceuticals

Name of active substance Trade name Affected micronutrients
Isoniazid INH “Agepha“®, Rifoldin® Vitamin D, Vitamin B6, Niacin
Rifampicin Rifoldin® Vitamin D
Ethambutol Etibi® Zinc

 

Mechanism of interaction

Mechanism of interaction
Vitamin D The administration of vitamin D leads to an increased rate of phagocytosis and differentiation of monocytes into macrophages. The calcitriol-VDR complex promotes the formation of microbicidal cathelicidin LL-37, which in turn destroys the cell wall of Mycobacterium tuberculosis and thus leads to its cell death.
Isoniazid: Vitamin D deficiency occurs during medication with isoniazid as it inhibits the hepatic hydroxylation of cholecalciferol to calcidiol.
Rifampicin: The breakdown and metabolism of vitamin D in the liver is accelerated by rifampicin.
Vitamin A/Zinc In addition to vitamin D deficiency, patients with tuberculosis very often have a deficiency of vitamin A and zinc. Due to its immunoprotective properties, vitamin A can improve the effectiveness of antituberculotic drugs. Zinc does this by impairing the humoral and cellular immune system. Furthermore, a zinc deficiency leads to a disturbance in the balance of vitamin A.
Vitamin B6 By forming a Schiff base, isoniazid reduces the formation of the active pyridoxal 5-phosphate. This results in a vitamin B6 deficiency.
Niacin The described vitamin B6 reaction influences all further reactions of tryptophan metabolism. There is reduced formation of the cholinic acid necessary for niacin synthesis, resulting in a secondary niacin deficiency.
Zinc If ethambutol is taken, chelation with zinc and copper interferes with their balance. Among other things, zinc-induced visual disturbances can occur (blurred vision).

Consequences and possible symptoms of the interaction

Negative consequences of the interaction Possible symptoms
Vitamin D Decrease in vitamin D levels

  • Fatigue, weakness, insomnia
    Susceptibility to infection

  • Decrease in bone density, rickets, osteopenia; in children: Rickets with skeletal deformations, spinal deformations, delay of tooth breakthrough
  • Calcification of the vessels of the cardiovascular system, cardiac insufficiency
  • Increase in alkaline phosphatase in the blood, insufficient absorption of calcium and phosphate
  • ECG changes, tetanic muscle spasms (Trousseau sign); in children: increased nervousness and irritability
  • Reduced insulin secretion and increased risk for type 1 diabetes
  • Fertility problems
Vitamin A/Zinc Decrease in vitamin A and zinc levels
  • Weakening of immune competence
  • Increase in susceptibility to infection
  • Increased bacterial adhesion to the bronchial epithelium
Vitamin B6 Decrease in vitamin B6 levels
  • irritability, nervous and depressive mood, insomnia
  • Hyperhomocysteinemia, hypochromic microcytic anemia
  • Dermatitis, Glossitis, Stomatitis, Cheilosis
  • Paresis, ataxias (due to glutamate metabolism disorders)
  • Peripheral neuropathy, demyelination, sensory disorders, epileptic cramps, tremor
  • Immune depression, Muscular atrophy and weakness
Niacin Niacin level drop
  • Exhaustion, memory problems, muscle weakness, sleep problems
  • Encephalopathies (tremor, rigor, spastic paresis)
  • Susceptibility to infection
  • Glossitis, corner of the mouth rhagades, inflammation of the esophagus and GIT
  • Cracked, flaky skin, strong pigmentation, increased cornification, pellagra (dermatitis, diarrhea, dementia)
Positive consequences of the interaction Possible symptoms
Vitamin D Increase in effectiveness
  • Improvement of drug therapy
  • Tuberculosis healing improves
  • Increase in antimicrobial immunity

Recommended Supplementation

Medical substance Recommended supplementation Dosage
All Vitamin D 2000–5000 I.U./d p.o.
Vitamin A 5000 I.U./d p.o.
Zinc 15 mg/d p.o.
Isoniazid Vitamin B6 50–100 mg/d p.o.

Special instructions for use

Instructions for use
Vitamin D A combination with calcium is recommended. Ensure monitoring of status.
Niacin Vitamin B complex supplementation is recommended.
Zinc Monitor visual performance when taking ethambutol.
Delayed intake of ethambutol and mineral supplements is necessary.

References

References

Baciewicz AM, Self TH. Isoniazid interactions. South Med J. 1985 Jun;78(6):714-8.
Brodie MJ et al. Effect of rifampicin and isoniazid on vitamin D metabolism. Clin Pharmacol Ther. 1982 Oct;32(4):525-30.
Gröber U. Mikronährstoffe. Metabolic Tuning – Prävention – Therapie. 3. Auflage, 2011
Gröber U. Arzneimittel und Mikronährstoffe. Medikationsorientierte Supplementierung.
3. Akt. und erw. Auflage, 2014
Ishii N, Nishihara Y. Pellagra encephalopathy among tuberculous patients: its relation to isoniazid therapy. J Neurol Neurosurg Psychiatry. 1985 Jul;48(7):628-34.
Karyadi E et al. A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr. 2002 Apr;75(4):720-7.
Mutschler E. Arzneimittelwirkungen,9.Aufl.Wissenschaftliche Verlagsgesellschaft, Stuttgart 2008
Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980 Dec;61(4):191-6.
Stargrove Mitchell Bebel, Treasure Jonathan, McKee Dwight L.: Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. 2008
Zhou Y et al. Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats. Eur J Drug Metab Pharmacokinet. 2013 Mar;38(1):5-13. doi: 10.1007/s13318-012-0106-9. Epub 2012 Oct 23.

 

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