General MedicationsORALHigh Alert

Tizanidne hydrochloride

TIZANIDNE HYDROCHLORIDE

Standard Dose

2 DOSAGE AND ADMINISTRATION • Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved. ( 2.1 ) • Recommended starting dose: 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of 3 doses in 24 hours ( 2.2 ) • Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days; maximum total daily dosage is 36 mg ( 2.2 ) • Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms. Consistent administration with respect to food is recommended. If substitution between dosage forms is necessary, take into consideration these pharmacokinetic differences. ( 2.2 , 2.6 , 12.3 ) • Patients with renal impairment (creatinine clearance less than 25 mL/min) or hepatic impairment: use lower individual doses during titration. If higher doses are required, individual doses rather than dosing frequency should be increased. ( 2.3 , 2.4 ) • To discontinue tizanidine capsules, decrease dose slowly to minimize the risk of withdrawal adverse reactions ( 2.5 ) 2.1 Recommended Evaluation and Testing Before and After Initiating Tizanidine Capsules Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved [see Warnings and Precautions ( 5.2 )]. 2.2 Recommended Dosage The recommended starting dose is 2 mg by mouth every 6 to 8 hours, as needed, to a maximum of three doses in 24 hours. Dosage can be gradually increased every 1 to 4 days by 2 mg to 4 mg at each dose based on clinical response and tolerability. The maximum total daily dosage is 36 mg. Single doses greater than 16 mg have not been studied. There are pharmacokinetic differences when administering tizanidine capsule between the fed or fasted state [see Clinical Pharmacology ( 12.3 )]. Tizanidine capsules may be taken with or without food; however, consistent administration with respect to food is recommended to reduce variability in tizanidine plasma exposure. Because of the short duration of therapeutic effect, treatment with tizanidine capsules should be reserved for those daily activities and times when relief of spasticity is most important. 2.3 Recommended Dosage in Patients with Renal Impairment In patients with creatinine clearance less than 25 mL/min, use lower individual doses during titration. If higher doses are required, the individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. 2.4 Recommended Dosage in Patients with Hepatic Impairment In patients with hepatic impairment, use lower individual doses during titration. If higher doses are required, individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3) ]. 2.5 Discontinuation of Tizanidine Capsules When discontinuing tizanidine capsule, particularly in patients who have been receiving high doses for long periods or who may be on concomitant treatment with narcotics, decrease the dosage by 2 mg to 4 mg per day to minimize the risk of withdrawal adverse reactions [see Drug Abuse and Dependence ( 9.3 )]. 2.6 Switching Between With/Without Food and Different Tizanidine Dosage Forms There are pharmacokinetic differences when: 1) switching between administration of tizanidine with or without food 2) switching between dosage forms if being administered with food. If these situations occur, monitor patients for therapeutic effect or adverse reactions [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )].

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Tizanidine capsules are indicated for the treatment of spasticity in adults.

Summary

Indications and usage 1 INDICATIONS AND USAGE Tizanidine capsules are indicated for the treatment of spasticity in adults.

Tizanidine capsules are a central alpha-2-adrenergic agonist indicated for the treatment of spasticity. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION • Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved. ( 2.1 ) • Recommended starting dose: 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of 3 doses in 24 hours ( 2.2 ) • Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days; maximum total daily dosage is 36 mg ( 2.2 ) • Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Tizanidine capsules are indicated for the treatment of spasticity in adults. Tizanidine capsules are a central alpha-2-adrenergic agonist indicated for the treatment of spasticity. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION • Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved. ( 2.1 ) • Recommended starting dose: 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of 3 doses in 24 hours ( 2.2 ) • Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days; maximum total daily dosage is 36 mg ( 2.2 ) • Tizanidine pharmacokinetics differs between tablets and capsules, and when taken with or without food. These differences could result in a change in tolerability and control of symptoms. Consistent administration with respect to food is recommended. If substitution between dosage forms is necessary, take into consideration these pharmacokinetic differences. ( 2.2 , 2.6 , 12.3 ) • Patients with renal impairment (creatinine clearance less than 25 mL/min) or hepatic impairment: use lower individual doses during titration. If higher doses are required, individual doses rather than dosing frequency should be increased. ( 2.3 , 2.4 ) • To discontinue tizanidine capsules, decrease dose slowly to minimize the risk of withdrawal adverse reactions ( 2.5 ) 2.1 Recommended Evaluation and Testing Before and After Initiating Tizanidine Capsules Monitoring of aminotransferase levels is recommended at baseline and 1 month after maximum dose is achieved [see Warnings and Precautions ( 5.2 )]. 2.2 Recommended Dosage The recommended starting dose is 2 mg by mouth every 6 to 8 hours, as needed, to a maximum of three doses in 24 hours. Dosage can be gradually increased every 1 to 4 days by 2 mg to 4 mg at each dose based on clinical response and tolerability. The maximum total daily dosage is 36 mg. Single doses greater than 16 mg have not been studied. There are pharmacokinetic differences when administering tizanidine capsule between the fed or fasted state [see Clinical Pharmacology ( 12.3 )]. Tizanidine capsules may be taken with or without food; however, consistent administration with respect to food is recommended to reduce variability in tizanidine plasma exposure. Because of the short duration of therapeutic effect, treatment with tizanidine capsules should be reserved for those daily activities and times when relief of spasticity is most important. 2.3 Recommended Dosage in Patients with Renal Impairment In patients with creatinine clearance less than 25 mL/min, use lower individual doses during titration. If higher doses are required, the individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. 2.4 Recommended Dosage in Patients with Hepatic Impairment In patients with hepatic impairment, use lower individual doses during titration. If higher doses are required, individual doses rather than dosing frequency should be increased [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3) ]. 2.5 Discontinuation of Tizanidine Capsules When discontinuing tizanidine capsule, particularly in patients who have been receiving high doses for long periods or who may be on concomitant treatment with narcotics, decrease the dosage by 2 mg to 4 mg per day to minimize the risk of withdrawal adverse reactions [see Drug Abuse and Dependence ( 9.3 )]. 2.6 Switching Between With/Without Food and Different Tizanidine Dosage Forms There are pharmacokinetic differences when: 1) switching between administration of tizanidine with or without food 2) switching between dosage forms if being administered with food. If these situations occur, monitor patients for therapeutic effect or adverse reactions [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )]. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine should not be used with other α2-adrenergic agonists ( 5.1 , 7.7) • 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 α2-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 su

Monitoring

• 5 WARNINGS AND PRECAUTIONS • Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; tizanidine should not be used with other α2-adrenergic agonists ( 5.1 , 7.7) • 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 α2-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.

Interaction Notes

• 7 DRUG INTERACTIONS 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 )].
• 7.2 Moderate or Weak CYP1A2 Inhibitors Concomitant use of tizanidine with moderate or weak CYP1A2 inhibitors (e.g., zileuton, antiarrhythmics [amiodarone, mexiletine, propafenone, and verapamil], cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided.