<p><strong>CYP inhibitors</strong>: The concomitant use of Tizanidine with moderate CYP1A2 inhibitors is not recommended. Caution should be exercised when Tizanidine is given with drugs known to increase the QT interval.<br />
<br />
<strong>Hypotension</strong>: Hypotension may occur during treatment with Tizanidine and also as a result of drug interactions with CYP1A2 inhibitors and/or antihypertensive drugs. Severe manifestations of hypotension such as loss of consciousness and circulatory collapse have also been observed.<br />
<br />
<strong>Withdrawal syndrome</strong>: Rebound hypertension and tachycardia have been observed after sudden withdrawal of Tizanidine, when it had been used chronically, and/or in high daily dosages, and/or concomitantly with antihypertensive drugs. In extreme cases, rebound hypertension might lead to cerebrovascular accident. Tizanidine should not be stopped abruptly, but rather gradually down titrated.<br />
<br />
<strong>Hepatic dysfunction</strong>: Since hepatic dysfunction has been reported in association with tizanidine, but rarely at daily doses up to 12 mg, it is recommended that liver function tests should be monitored monthly for the first four months in patients receiving doses of 12 mg and higher and in patients who develop clinical symptoms suggestive of hepatic dysfunction, such as unexplained nausea, anorexia or tiredness. Treatment with Tizanidine should be discontinued if serum levels of SGPT or SGOT are persistently above three times the upper limit of the normal range.<br />
<br />
<strong>Patients with renal impairment</strong>: In patients with renal impairment (creatinine clearance &lt;25 mL/min) systemic exposure to tizanidine may increase up to 6 times compared to patient with normal renal function. Therefore, it is recommended to start treatment at 2 mg once daily.<br />
<br />
<strong>Hypersensitivity reactions</strong>: Hypersensitivity reactions including anaphylaxis, angioedema, dermatitis, rash, urticarial, pruritis and erythema have been reported in association with tizanidine. Careful observation of the patient is recommended for one to two days after the first dose is administered. If anaphylaxis or angioedema with anaphylactic shock or difficulty of breathing is observed treatment with Tizanidine should be discontinued immediately and appropriate medical treatment should be instituted.<br />
<br />
<strong>Driving and using machines</strong>: Patients experiencing somnolence, dizziness or any signs or symptoms of hypotension should refrain from activities requiring a high degree of alertness, e.g. driving a vehicle or operating machines.</p>