Tizanidne hydrochloride
Generic: TIZANIDNE HYDROCHLORIDE
Basic Information
Manufacturer
Preferred Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
3f569c5a-ec9d-4356-ac04-c17714ff68d1
Indications & 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 )
Tizanidine capsules are a central alpha-2-adrenergic agonist indicated for the treatment of spasticity.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS 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 Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
The safety of tizanidine has been evaluated in three double-blind, randomized, placebo-controlled clinical studies [see Clinical Studies ( 14 )].
Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury.
Each study had a 13-week active treatment period which included a 3-week titration phase to the maximum tolerated dose up to 36 mg/day in three divided doses, a 9-week plateau phase where the dose of tizanidine was held constant and a 1-week dose tapering period.
In all, 264 patients received tizanidine and 261 patients received placebo.
Across the three studies approximately 51% of patients were women, and the median dose during the plateau phase ranged from 20 to 28 mg/day.
The most common adverse reactions (greater than 10% of patients treated with tizanidine) reported in multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness), and dizziness.
Three-quarters of the patients rated the reactions as mild to moderate and one-quarter of the patients rated the reactions as being severe.
These adverse reactions appeared to be dose related.
Table 1 lists adverse reactions that were reported in greater than 2% of patients in three multiple dose, placebo-controlled studies who received tizanidine where the frequency in the tizanidine group was greater than the placebo group.
Table 1: Multiple Dose, Placebo-Controlled Studies—Adverse Reactions Reported in greater than 2% of Patients Treated with Tizanidine Tablets and Incidence Greater than Placebo Adverse Reaction Placebo N = 261% Tizanidine Tablet N = 264% Dry mouth 10 49 Somnolence 10 48 Asthenia* 16 41 Dizziness 4 16 UTI 7 10 Infection 5 6 Constipation 1 4 Liver test abnormality 2 6 Vomiting 0 3 Speech disorder 0 3 Amblyopia (blurred vision) Less than 1 3 Urinary frequency 2 3 Flu syndrome 2 3 Dyskinesia 0 3 Nervousness Less than 1 3 Pharyngitis 1 3 Rhinitis 2 3 *includes weakness, fatigue, and/or tiredness In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see Clinical Studies ( 14 )], the patients were specifically asked if they had experienced any of the four most common adverse reactions: dry mouth, somnolence (drowsiness), asthenia (weakness, fatigue and/or tiredness), and dizziness.
In addition, hypotension and bradycardia were observed.
The occurrence of these reactions is summarized in Table 2.
Other events were, in general, reported at a rate of 2% or less.
Table 2: Single Dose, Placebo-Controlled Study—Common Adverse Reactions Reported Adverse Reaction Placebo N = 48 % Tizanidine Tablet, 8 mg, N = 45 % Tizanidine Tablet, 16 mg, N = 49 % Somnolence 31 78 92 Dry mouth 35 76 88 Asthenia* 40 67 78 Dizziness 4 22 45 Hypotension 0 16 33 Bradycardia 0 2 10 *includes weakness, fatigue, and/or tiredness 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of tizanidine.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac Disorders: Ventricular tachycardia, decreased blood pressure Hepatobiliary Disorders: Hepatotoxicity [see Warnings and Precautions ( 5.2 )] , hepatitis Musculoskeletal and Connective Tissue Disorders: arthralgia Nervous System Disorders: Convulsion, paresthesia, tremor, muscle spasms Psychiatric Disorders: Hallucinations [see Warnings and Precautions ( 5.4 )], depression Skin and Subcutaneous Tissue Disorders: Stevens Johnson Syndrome, anaphylactic reaction [see Warnings and Precautions ( 5.5) ] , exfoliative dermatitis, rash
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
The safety of tizanidine has been evaluated in three double-blind, randomized, placebo-controlled clinical studies [see Clinical Studies ( 14 )].
Two studies were conducted in patients with multiple sclerosis and one in patients with spinal cord injury.
Each study had a 13-week active treatment period which included a 3-week titration phase to the maximum tolerated dose up to 36 mg/day in three divided doses, a 9-week plateau phase where the dose of tizanidine was held constant and a 1-week dose tapering period.
In all, 264 patients received tizanidine and 261 patients received placebo.
Across the three studies approximately 51% of patients were women, and the median dose during the plateau phase ranged from 20 to 28 mg/day.
The most common adverse reactions (greater than 10% of patients treated with tizanidine) reported in multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness), and dizziness.
Three-quarters of the patients rated the reactions as mild to moderate and one-quarter of the patients rated the reactions as being severe.
These adverse reactions appeared to be dose related.
Table 1 lists adverse reactions that were reported in greater than 2% of patients in three multiple dose, placebo-controlled studies who received tizanidine where the frequency in the tizanidine group was greater than the placebo group.
Table 1: Multiple Dose, Placebo-Controlled Studies—Adverse Reactions Reported in greater than 2% of Patients Treated with Tizanidine Tablets and Incidence Greater than Placebo Adverse Reaction Placebo N = 261% Tizanidine Tablet N = 264% Dry mouth 10 49 Somnolence 10 48 Asthenia* 16 41 Dizziness 4 16 UTI 7 10 Infection 5 6 Constipation 1 4 Liver test abnormality 2 6 Vomiting 0 3 Speech disorder 0 3 Amblyopia (blurred vision) Less than 1 3 Urinary frequency 2 3 Flu syndrome 2 3 Dyskinesia 0 3 Nervousness Less than 1 3 Pharyngitis 1 3 Rhinitis 2 3 *includes weakness, fatigue, and/or tiredness In the single dose, placebo-controlled study involving 142 patients with spasticity due to multiple sclerosis (Study 1) [see Clinical Studies ( 14 )], the patients were specifically asked if they had experienced any of the four most common adverse reactions: dry mouth, somnolence (drowsiness), asthenia (weakness, fatigue and/or tiredness), and dizziness.
In addition, hypotension and bradycardia were observed.
The occurrence of these reactions is summarized in Table 2.
Other events were, in general, reported at a rate of 2% or less.
Table 2: Single Dose, Placebo-Controlled Study—Common Adverse Reactions Reported Adverse Reaction Placebo N = 48 % Tizanidine Tablet, 8 mg, N = 45 % Tizanidine Tablet, 16 mg, N = 49 % Somnolence 31 78 92 Dry mouth 35 76 88 Asthenia* 40 67 78 Dizziness 4 22 45 Hypotension 0 16 33 Bradycardia 0 2 10 *includes weakness, fatigue, and/or tiredness 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of tizanidine.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac Disorders: Ventricular tachycardia, decreased blood pressure Hepatobiliary Disorders: Hepatotoxicity [see Warnings and Precautions ( 5.2 )] , hepatitis Musculoskeletal and Connective Tissue Disorders: arthralgia Nervous System Disorders: Convulsion, paresthesia, tremor, muscle spasms Psychiatric Disorders: Hallucinations [see Warnings and Precautions ( 5.4 )], depression Skin and Subcutaneous Tissue Disorders: Stevens Johnson Syndrome, anaphylactic reaction [see Warnings and Precautions ( 5.5) ] , exfoliative dermatitis, rash