<p>Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. The increased plasma levels of tizanidine may result in overdose symptoms such as QT(c) prolongation. Concomitant administration of drugs known to induce the activity of CYP1A2 may decrease the plasma levels of tizanidine. The decreased plasma levels of tizanidine may reduce the therapeutic effect of Tizanidine.<br />
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<strong>Observed interactions resulting in a contraindication</strong>: Concomitant use of Tizanidine with fluvoxamine or ciprofloxacin, both CYP1A2 inhibitors is contraindicated. Concomitant use of Tizanidine with fluvoxamine or ciprofloxacin resulted in a 33-fold and 10-fold increase in tizanldine AUC, respectively. Clinically significant and prolonged hypotension may result along with somnolence, dizziness and decreased psychomotor performance. The increased plasma levels of tizanidine may result in overdose symptoms such as QT(c) prolongation.<br />
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<strong>Observed interactions resulting in concomitant use not recommended</strong>: Co administration of Tizanidine with other inhibitors of CYP1A2 such as antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, and ticlopidine is not recommended.<br />
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<strong>Observed interactions to be considered</strong>: Caution should be exercised when Tizanidine is given with drugs known to prolong the QT interval (including but not limited to cisapride, amytriptyline and azithromycin).<br />
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<strong>Antihypertensives</strong>: Concomitant use of Tizanidine with antihypertensives, including diuretics, may occasionally cause hypotension and bradycardia. In some patients rebound hypertension and tachycardia have been observed upon abrupt discontinuation of Tizanidine when concomitantly used with antihypertensive drugs. In extreme cases, rebound hypertension might lead to cerebrovascular accident.<br />
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<strong>Rifampicin</strong>: Concomitant administration of Tizanidine with rifampicin results in 50% decrease in tizanidine concentrations. Therefore, the therapeutic effects of Tizanidine may be reduced during treatment with rifampicin, which may be of clinical significance in some patients. Long term coadministration should be avoided and if co- administration is considered a careful dose adjustment (increase) may be required.&nbsp;<br />
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<strong>Cigarette smoke</strong>: Administration of Tizanidine in smokers (&gt;10 cigarettes per day) results in about 30% decrease in tizanidine systemic exposure. Long-term therapy with Tizanidine in heavy smokers may require higher doses than the average doses.<br />
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<strong>Alcohol</strong>: While on Tizanidine therapy, alcohol consumption should be minimized or avoided as it may increase the potential for adverse events (e.g. sedation and hypotension). The central nervous system depressant effects of alcohol may be enhanced by Tizanidine.<br />
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<strong>Anticipated interactions to be considered</strong>: Sedatives, hypnotics (e.g. benzodiazepine or baclofen), and another drug such as antihistamines may enhance the sedative action of tizanidine. Tizanidine should be avoided when using with other alpha-2 adrenergic agonists (such as clonidine) because of their potential additive hypotensive effect.</p>