The first FDA approved oral solution of tizanidine, an effective medicine doctors use to treat muscle spasticity in adults.
Ask your healthcare provider if ONTRALFY® may be right for you.
References:
ONTRALFY® (tizanidine oral solution) is a central alpha-2-adrenergic agonist indicated for the treatment of spasticity in adults. (1)
CONTRAINDICATIONS:
ONTRALFY is contraindicated in patients:
WARNINGS AND PRECAUTIONS:
Hypotension
ONTRALFY 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.
Monitor for hypotension when ONTRALFY is used in patients receiving concurrent antihypertensive therapy. It is not recommended that ONTRALFY be used with other α2-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 ONTRALFY with strong CYP1A2 inhibitors is contraindicated [see Contraindications (4) and Drug Interactions (7.1)]. (5.1)
Liver Injury
ONTRALFY may cause hepatocellular liver injury. Liver function test abnormality and hepatotoxicity have been observed with tizanidine, the active moiety of ONTRALFY [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)]. (5.2)
Sedation
ONTRALFY 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 ONTRALFY with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions (7.4)]. Monitor patients who take ONTRALFY with another CNS depressant for symptoms of excess sedation. (5.3)
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 of tizanidine. 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 ONTRALFY in patients who develop hallucinations. (5.4)
Hypersensitivity Reactions
ONTRALFY can cause anaphylaxis. Signs and symptoms of hypersensitivity, including respiratory compromise, urticaria, and angioedema of the throat and tongue, have been reported. ONTRALFY is contraindicated in patients with a history of hypersensitivity reactions to tizanidine [see Contraindications (4)]. (5.5)
Withdrawal Adverse Reactions
ONTRALFY 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 ONTRALFY (20 to 28 mg daily) for long periods of time (9 weeks or more) or who may be on concomitant treatment with narcotics, the ONTRALFY dosage should be decreased slowly [see Dosage and Administration (2.5)]. (5.6)
ADVERSE REACTIONS:
The following clinically significant adverse reactions are described elsewhere in other sections of the prescribing information:
The most common adverse reactions (in greater than 10% of patients taking tizanidine) were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness), and dizziness. (6.1)
DRUG INTERACTIONS:
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)]. (7.1)
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)]. (7.2)
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)]. (7.3)
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)]. (7.4)
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)]. (7.5)
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. (7.6)
USE IN SPECIFIC POPULATIONS:
Pregnancy
There are no adequate data on the developmental risk associated with use of tizanidine in pregnant women. See Full Prescribing Information for animal data. (8.1)
Lactation
There are no data on the presence of tizanidine in human milk, the effects on the breastfed infant, or the effects on human milk production. Animal studies have reported the presence of tizanidine in the milk of lactating animals.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ONTRALFY and any potential adverse effects on the breastfed infant from ONTRALFY or from the underlying maternal condition. (8.2)
Females and Males of Reproductive Potential
There are no adequate and well-controlled studies in humans on the effect of ONTRALFY on female or male reproductive potential. Oral administration of tizanidine to male and female rats resulted in adverse effects on fertility [see Nonclinical Toxicology (13.1)]. (8.3)
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. See Full Prescribing Information for juvenile animal toxicity data. (8.4)
Geriatric Use
Tizanidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (8.5)
Renal Impairment
In patients with renal insufficiency (creatinine clearance < 25 mL/min), clearance of tizanidine was reduced [see Clinical Pharmacology (12.3)]. In these patients, dosage reduction is recommended [see Dosage and Administration (2.3)]. Because the risk of adverse reactions to ONTRALFY may be greater in patients with impaired renal function, monitor these patients closely for the onset or increase in severity of common adverse reactions [see Adverse Reactions (6.1)]. (8.6)
Hepatic Impairment
ONTRALFY should be used with caution in patients with hepatic impairment. The influence of hepatic impairment on the pharmacokinetics of tizanidine has not been evaluated. Because tizanidine is extensively metabolized in the liver, hepatic impairment would be expected to have significant effects on pharmacokinetics of tizanidine [see Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)]. In patients with hepatic impairment, dosage reduction is recommended [see Dosage and Administration (2.4)]. (8.7)
REFERENCES:
1. ONTRALFY Prescribing Information PI-TIZ-01-001. Rosemont Pharmaceuticals, LLC; 2025
This Important Safety Information does not include all the information needed to use ONTRALFY safely and effectively. Click here for Full Prescribing Information.
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
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