Tizanidine: uses, appearance and warnings

Tizanidine tablets are indicated for the treatment of spasticity in adults. Tizanidine tablets are a central alpha-2-adrenergic agonist indicated for the treatment of spasticity. ( 1 )

2 mg: White to off-white, round, scored tablets debossed with ‘2 over TI’ on one side of the tablet and scored on the other side. 4 mg: White to off-white, round, scored tablets debossed with ‘4 over TI’ on one side of the tablet and quadrisect scored on the other side. Tablets: 2 mg and 4 mg ( 3 )

16.1 How Supplied Tizanidine tablets, USP are available as white to off-white, round tablets containing 2 mg or 4 mg of tizanidine. Tizanidine Tablets USP, 2 mg are white to off-white, round, scored tablets debossed with ‘2 over TI’ on one side of the tablet and scored on the other side. They are supplied as: Bottles of 150 NDC 84386-023-77 Bottles of 1,000 NDC 84386-023-99 Tizanidine Tablets USP, 4 mg are white to off-white, round, scored tablets debossed with ‘4 over TI’ on one side of the tablet and quadrisect scored on the other side. They are supplied as: Bottles of 150 NDC 84386-024-77 Bottles of 1,000 NDC 84386-024-99 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Dispense in containers with child resistant closure.

Tizanidine tablets are contraindicated in patients: taking strong CYP1A2 inhibitors [see Drug Interactions (7.1) ] . with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets. Symptoms have included anaphylaxis and angioedema [see Warnings and Precautions (5.5) ]. Concomitant use with strong CYP1A2 inhibitors ( 4 , 7.1 ) Patients with a history of hypersensitivity to tizanidine or the ingredients in tizanidine tablets ( 4 , 5.5 )

Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.5 ) Risk of liver injury: monitor ALTs; discontinue tizanidine if liver injury occurs ( 5.2 ) Sedation: Tizanidine may interfere with everyday activities; sedative effects of tizanidine, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 ) Hallucinations: consider discontinuation of tizanidine ( 5.4 ) 5.1 Hypotension Tizanidine is an α 2 -adrenergic agonist that can produce hypotension [see Adverse Reactions (6.1) and Drug Interactions (7.5) ] . Syncope has been reported in patients treated with tizanidine in the postmarketing setting. The risk of hypotension may be minimized by dose titration; monitoring for signs and symptoms of hypotension prior to dosage increase may minimize the risks associated with hypotension. In addition, patients moving from a supine to fixed upright position may be at increased risk for hypotension and orthostatic effects. Monitor for hypotension when tizanidine is used in patients receiving concurrent antihypertensive therapy. It is not recommended that tizanidine be used with other α 2 -adrenergic agonists. Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of tizanidine and strong CYP1A2 inhibitors [see Clinical Pharmacology (12.3) ]. Therefore, concomitant use of tizanidine with strong CYP1A2 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1) ] . 5.2 Liver Injury Tizanidine may cause hepatocellular liver injury. Liver function test abnormality and hepatotoxicity have been observed with tizanidine [see Adverse Reactions (6.1 , 6.2) ]. Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected [see Dosage and Administration (2.1) and Use in Specific Populations (8.7) ]. 5.3 Sedation Tizanidine can cause sedation, which may interfere with everyday activity. In the multiple dose studies of tizanidine, the prevalence of patients with sedation peaked following the first week of titration and then remained stable for the duration of the maintenance phase of the study [see Adverse Reactions (6.1) ] . The CNS depressant effects of tizanidine with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions (7.4) ]. Monitor patients who take tizanidine with another CNS depressant for symptoms of excess sedation. 5.4 Hallucinosis/Psychotic-Like Symptoms Tizanidine use has been associated with hallucinations. Formed, visual hallucinations or delusions were reported in 5 of 170 patients (3%) in two North American controlled clinical studies. Most of the patients were aware that the events were unreal. One patient developed psychosis in association with the hallucinations. One patient among these 5 continued to have problems for at least 2 weeks following discontinuation of tizanidine. Hallucinations have also been reported with tizanidine use in the postmarketing setting. Consider discontinuing tizanidine in patients who develop hallucinations. 5.5 Hypersensitivity Reactions Tizanidine can cause anaphylaxis. Signs and symptoms of hypersensitivity, including respiratory compromise, urticaria, and angioedema of the throat and tongue, have been reported. Tizanidine tablets are contraindicated in patients with a history of hypersensitivity reactions to tizanidine [see Contraindications (4) ]. 5.6 Withdrawal Adverse Reactions Tizanidine can cause withdrawal adverse reactions, which include rebound hypertension, tachycardia, and hypertonia. To minimize the risk of these reactions, particularly in patients who have been receiving high doses of tizanidine (20 to 28 mg daily) for long periods of time (9 weeks or more) or who may be on concomitant treatment with narcotics, the tizanidine dosage should be decreased slowly [see Dosage and Administration (2.5) ].

The following clinically significant adverse reactions are described elsewhere in other sections of the prescribing information: Hypotension [see Warnings and Precautions (5.1) ] Liver Injury [see Warnings and Precautions (5.2) ] Sedation [see Warnings and Precautions (5.3) ] Hallucinosis/Psychotic-Like Symptoms [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Withdrawal Adverse Reactions [see Warnings and Precautions (5.6) ] The most common adverse reactions (greater than 10% of patients taking tizanidine and greater than in patients taking placebo) were dry mouth, somnolence, asthenia, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Moderate or weak CYP1A2 inhibitors: avoid concomitant use; may cause hypotension, bradycardia, or excessive drowsiness; if concomitant use is necessary and adverse reactions occur, reduce tizanidine dosage or discontinue. ( 7.2 , 12.3 ) 7.1 Strong CYP1A2 Inhibitors Concomitant use of tizanidine with strong cytochrome P450 1A2 (CYP1A2) inhibitors (e.g., fluvoxamine, ciprofloxacin) is contraindicated. Changes in pharmacokinetics of tizanidine when administered with a strong CYP1A2 inhibitor resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications (4) and Clinical Pharmacology (12.3) ]. …