Tizanidine Ciprofloxacin

TIZANIDINE ANTIBIOTICS-CIPROFLOXACIN T tizanidine levels Tizanidine is a substrate for CYP1A2 ciprofloxacin is a potent inhibitor of CYP1A2 and is thought to inhibit its presystemic metabolism, resulting in t absorption and t levels of tizanidine Avoid co-administration... 

Fluvoxamine causes a very marked 33-fold increase in tizanidine levels with a consequent increase in hypotensive and sedative effects. The combination is potentially hazardous and should be avoided. Ciprofloxacin markedly increases tizanidine levels and adverse effects, and particular caution is required if this combination is considered essential Combined oral contraceptives increase tizanidine levels fourfold and might increase adverse effects. other inhibitors of CYP1A2 are predicted to interact similarly. 

In a placebo-controlled, crossover study in 10 healthy subjects ciprofloxacin 500 mg twice daily for 3 days markedly increased the AUC of a single 4-mg dose of tizanidine by tenfold and the maximum level by sevenfold, without significantly affecting the half-life. The hypotensive and sedative effects of tizanidine were also markedly increased by ciprofloxacin. ... 

A 45-year-old Japanese woman with multiple sclerosis taking tizanidine 3 mg daily had a reduction in blood pressure (from 124/88 to 102/74 mniHg) and heart rate (from 86 to 58 bpm) shortly after starting to take ciprofloxacin 400 mg daily. After 2 days she complained of drowsiness and her blood pressure was 92/54 mmHg. Retrospective analysis revealed 8 patients who had received tizanidine and ciprofloxacin concurrently. In these patients, the mean reduction in blood pressure on starting ciprofloxacin was 21.3/15.4 mmHg, and the heart rate reduction was 14.9 bpm. Adverse effects attributable to tizanidine occurred in three of the patients. ... 

Tizanidine is a substrate of the cytochrome P450 isoenzyme CYP1A2, which undergoes substantial presystemic metabolism by this isoenzyme. Ciprofloxacin appears to inhibit mainly the presystemic metabolism leading to increased absorption, as reflected by the increase in maximum level without a change in elimination half-life. Rofecoxib and fluvoxamine inhibited both presystemic metabolism and the elimination phase. Fluvoxamine, which is a known potent inhibitor of CYP1A2, had the most marked effect. The contraceptive steroids were modest inhibitors of CYP1A2 by comparison. 

For ciprofloxacin, there is a marked tenfold increase in exposure to tizanidine, with a consequent increase in adverse effects. Some authors recommend that this combination be avoided, whereas others recommend caution. The US manufacturer contraindicates the combination, whereas the UK manufacturers do not mention this potential interaction. If ciprofloxacin is considered the most appropriate antibacterial to use in a patient already taking tizanidine, anticipate the need to reduce the tizanidine dose before starting the ciprofloxacin, and closely monitor adverse effects starting ciprofloxacin may cause marked hypotension, bradycardia, and sedation. Other quinolones also inhibit CYP1A2, but to varying degrees, see Table 33.4 , (p. 1193). 

Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 lA2-medi-ated presystemic metabolism. Clin Pharmacol Ther (2004) 76, 598-606. 

Momo K, Homma M, Kohda Y, Ohkoshi N, Yoshizawa T, Tamaoka A. Drug interaction of tizanidine and ciprofloxacin case report Clin Pharmacol Ther 2006) 80, 717-9. 

Are there contraindications to concomitant drug use For instance, tizanidine is contraindicated in patients with concomitant use of CYP450 1A2 inhibitors such as fluvoxamine, amiodarone, mexiletine, propafenone, cimetidine, fluoroquinolones (ciprofloxacin, norfloxacin), rofecoxib, oral contraceptives, and ticlopidine [27]. 

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