ontralfy

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 ) The pharmacokinetics of Ontralfy differ 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. ( 2.2 , 12.3 ) Patients with renal impairment (creatinine clearance <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 Ontralfy, decrease dose by 2 mg (5 mL) to 4 mg (10 mL) per day to minimize the risk of withdrawal adverse reactions. ( 2.5 ) 2.1 Recommended Evaluation and Testing Before and After Initiating Ontralfy 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 (5 mL) 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…

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 Rosemont Pharmaceuticals, LLC at 1-844-638-2235 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 practice. The safety of Ontralfy has been established from adequate and well-controlled studies of tizanidine tablets in adult patients with spasticity [see Clinical Studies (14) ] . Below is a presentation of the adverse reactions of tizanidine tablets in these adequate and well-controlled…

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 ingredients in Ontralfy ( 4 , 5.5 )

A review of the safety surveillance database revealed cases of intentional and accidental tizanidine overdose. Some of the cases resulted in fatality and many of the intentional overdoses were with multiple drugs including CNS depressants. The clinical manifestations of tizanidine overdose were consistent with its known pharmacology. In the majority of cases a decrease in sensorium was observed including lethargy, somnolence, confusion and coma. Depressed cardiac function is also observed including most often bradycardia and hypotension. Respiratory depression is another common feature of tizanidine overdose. Should overdose occur, ensure the adequacy of an airway and monitor cardiovascular and respiratory function. Dialysis is not likely to be an efficient method of removing tizanidine from the body [see Description (11) ]. In general, symptoms resolve within one to three days following discontinuation of tizanidine and administration of appropriate therapy. Because of the similar mechanism of action, symptoms and management of tizanidine overdose are similar to that following clonidine overdose. For the most recent information concerning the management of overdose, contact a poison control center.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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) 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 Ontralfy 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. If concomitant use is clinically necessary, and adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce Ontralfy dosage or discontinue Ontralfy therapy [see Clinical Pharmacology (12.3) ]. 7.3 Oral Contraceptives Concomitant use of Ontralfy with oral contraceptives is not recommended. However, if concomitant use is clinically necessary and adverse reactions such as hypotension, bradycardia, or excessive drowsiness occur, reduce or discontinue Ontralfy therapy [see Clinical Pharmacology (12.3) ]. 7.4 Alcohol and Other CNS Depressants Alcohol increases the exposure of tizanidine after administration of Ontralfy. This was associated with an increase in adverse reactions of tizanidine. Concomitant use of Ontralfy with CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may cause additive CNS depressant effects, including sedation. Monitor patients who take Ontralfy with another CNS depressant for symptoms of excess sedation [see Clinical Pharmacology (12.3) ]. 7.5 α2-Adrenergic Agonists Concomitant use of Ontralfy with other α2-adrenergic agonists is not recommended because hypotensive effects may be cumulative [see Warnings and Precautions (5.1) ]. 7.6 Antihypertensive Medications Concomitant use of Ontralfy with antihypertensive medications may cause additive hypotensive effects [see Warnings and Precautions (5.1) ] . Monitor patients who take Ontralfy with antihypertensive medications for hypotension.