Monograph
J01AA07 - Tetracycline |
Propably not porphyrinogenic |
PNP |
Rationale
Tetracycline is mainly excreted unchanged in urine and faeces. In vitro studies have indicated that tetracycline is a substrate and an inhibitor of CYP 3A4, but this is probably to a minor degree and of clinical insignificance.
Tetracycline is not suspected to be an inducer or a mechanism based inhibitor of any CYP enzymes.
Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in carbohydrate intake.
Chemical description
Tetracycline is an antibiotic derived from Streptomyces aureofaciens.
Therapeutic characteristics
Tetracycline is a bacteriostatic broad-spectrum antibiotic, indicated for the treatment of a variety of infections. It may be administered orally or intravenously. Tetracycline may cause gastrointestinal discomfort.
Metabolism and pharmacokinetics
Tetracycline is mainly excreted unchanged in urine and in faeces. When given orally, up to 77% of the dose is absorbed, and about 60 % of the administered dose is excreted in the urine. Tetracycline is a substrate for P-glycoprotein (Kim 2002). It has a half-life of 6-12 hours.
In vitro studies have shown that tetracycline is a substrate and an inhibitor of CYP 3A4 (Zhao 1997, 1999). A mechanism of this inhibition is not suggested, but tetracycline is not listed as a mechanism-based inhibitor of CYP enzymes.
In vivo studies have shown no interaction between tetracycline and oral contraceptives (Murphy 1991). This suggests that the inhibition of CYP 3A4 is not clinically significant. Tetracycline is not listed as an inducer of CYP enzymes.
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | American College of Obstetricians and Gynecologists. The use of hormonal contraception in women with coexisting medical conditions. ACOG Practice Bulletin 73,
Obstet Gynecol. 2006 Jun;107(6):1453-72. |
|
| 2. | Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines.
Agwuh KN, MacGowan A. J Antimicrob Chemother. 2006 Aug; 58 (2):256-65. |
16816396 |
| 3. | Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics. Br J Clin Pharmacol 1988;25:527-32.
Back DJ, Grimmer SF, et al. |
3408633 |
| 4. | Drugs as P-glycoprotein substrates, inhibitors, and inducers.
Kim RB. Drug Metab Rev. 2002 Feb-May;34(1-2):47-54. |
|
| 5. | The effect of tetracycline on levels of oral contraceptives. Am J Obstet Gynecol 1991;164:28-33.
Murphy AA, Zacur HA, et al. |
1986620 |
| 6. | A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition.
Zhao XJ, Ishizaki T. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep; 24(3):272-8. |
10716067 |
| 7. | Metabolic interactions of selected antimalarial and non-antimalarial drugs with the major pathway (3-hydroxylation) of quinine in human liver microsomes.
Zhao XJ, Ishizaki T. Br J Clin Pharmacol. 1997 Nov; 44(5):505-11. |
9384469 |
| * | Drug interaction databases | |
| 8. | Lexicomp Online. Martindale: The Complete Drug Reference. Tetracycline. (last updated: 01.15.2013 )
|
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| * | Summary of Product Characteristics | |
| 9. | Norwegian medicines agency. Summary of Product Characteristics (SPC). (Tetracyclin Arco).
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| 10. | The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Tetracycline tablets BP 250mg.
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