ONTRALFY (tizanidine hydrochloride)

Tizanidine has linear pharmacokinetics over the doses studied in clinical development [1 mg (half the recommended dosage) to 20 mg]. Ontralfy oral solution has comparable bioavailability to tizanidine oral tablets under fasted and fed conditions and to tizanidine oral capsules under the fed condition.

AbsorptionFollowing oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass...

The efficacy of Ontralfy is supported by evidence from a relative bioavailability study in healthy adult subjects comparing Ontralfy to tizanidine tablets under fasted and fed conditions [see Clinical Pharmacology (12.3) ]. The clinical studies described below were conducted using tizanidine tablets. The efficacy of tizanidine for the treatment of spasticity was demonstrated in two adequate and well-controlled studies in patients with multiple sclerosis or spinal cord injury (Studies 1 and 2). Single-Dose Study in Patients with Multiple Sclerosis with Spasticity In Study 1, 140 patients with s...

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 ...

Ontralfy is contraindicated in patients: taking strong CYP1A2 inhibitors [see Drug Interactions (7.1) ]. with a history of hypersensitivity to tizanidine or the ingredients in Ontralfy. 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 ing...

Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Ontralfy should not be used with other α 2 -adrenergic agonists. ( 5.1 , 7.5) Risk of liver injury: monitor ALTs; discontinue Ontralfy if liver injury occurs. ( 5.2 ) Sedation: Ontralfy may interfere with everyday activities; sedative effects of Ontralfy, alcohol, and other central nervous system (CNS) depressants are additive. ( 5.3 , 7.4 ) Hallucinations: consider disco...

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 Ontralfy dosage or discontinue. ( 7.2 , 12.3 ) 7.1 Strong CYP1A2 Inhibitors Concomitant use of Ontralfy with strong cytochrome P450 1A2 (CYP1A2) inhibitors (e.g., fluvoxamine, ciprofloxacin) i...