Safety and Tolerability
Digestive related adverse events including nausea, vomiting, and diarrhea were significantly higher in patients receiving tigecycline in clinical trials than those receiving comparator agents.[45,46] Treatment emergent events from cSSI and cIAI trials are summarized in Table 3 . A small number of patients discontinued tigecycline due to treatment emergent adverse events experienced during therapy (n = 41). This was not statistically different from patients in comparator groups but was most commonly due to gastrointestinal upset (n = 10).
There were no patients that developed Clostridium difficile infection in clinical trials and additional evidence suggests that there is a low risk of C. difficile induction associated with tigecycline.[46,47,48] One study reported that, despite alterations of normal microflora following tigecycline exposure in a human gut model, there was no evidence of C.difficile proliferation or toxin production. The authors suggested that this result may be due to the potency of tigecycline against C. difficile, which has also been documented elsewhere.
There is minimal hepatic metabolism of tigecycline and no entry into cytochrome P450 metabolic pathways. Therefore, the potential for drug interactions appears to be low. Studies have been conducted to assess the drug-interaction potential of tigecycline with both warfarin and digoxin.[57,58] In the warfarin study, 13 healthy patients received tigecycline as a 100-mg loading dose and 50mg every 12h thereafter for 8 days. Warfarin was administered as a 25-mg dose on day 1 and a 25-mg dose on day 5. The concurrent administration of these agents resulted in higher concentrations of the S and R warfarin isomers but did not significantly affect the international normalization ratio (INR) of the subjects. Of note, nonclinical dosing of warfarin was utilized in this study and it is recommended to monitor INR values in patients with concurrent administration of tigecycline and warfarin.
Tigecycline and digoxin have also been coadministered in healthy men. Tigecycline did not affect the AUC of digoxin and tigecycline pharmacokinetic parameters were unaffected.
Due to structural similarities with tetracycline antimicrobials, associated adverse effects with tigecycline may occur. These include photosensitivity and tooth discoloration when used in children in stages of tooth development. As a result, tigecycline is also not recommended for use in pregnant women.
Expert Rev Anti Infect Ther. 2008;6(5):557-567. © 2008 Expert Reviews Ltd.
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Cite this: Establishing the Role of Tigecycline in an era of Antimicrobial Resistance - Medscape - Oct 01, 2008.