FLEQSUVY

1 INDICATIONS AND USAGE FLEQSUVY is indicated for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. FLEQSUVY may also be of some value in patients with spinal cord injuries and other spinal cord diseases. Limitations of Use FLEQSUVY is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders. FLEQSUVY is a gamma-aminobutyric acid (GABA-ergic) agonist indicated for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. ( 1 ) FLEQSUVY may also be of some value in patients with spinal cord injuries and other spinal cord diseases. ( 1 ) Limitations of Use FLEQSUVY is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders. ( 1 )

2 DOSAGE AND ADMINISTRATION FLEQSUVY is a concentrated formulation. Verify the dose of the product prior to dispensing. ( 2.1 ) Initiate FLEQSUVY with a low dosage, preferably in divided doses, administered orally. Increase gradually based on clinical response and tolerability. ( 2.2 ) The maximum dosage is 80 mg daily (20 mg four times a day). ( 2.2 ) When discontinuing, reduce the dosage slowly. ( 2.3 ) 2.1 Important Information FLEQSUVY is a concentrated formulation. Verify the strength and the dose of the product prior to prescribing, dispensing, and administering. 2.2 Recommended Dosage Initiate FLEQSUVY with a low dosage, preferably in divided doses, administered orally. The following gradually increasing dosage regimen is suggested, but should be adjusted based on clinical response and tolerability: 1 mL (5 mg) three times a day for three days 2 mL (10 mg) three times a day for three days 3 mL (15 mg) three times a day for three days 4 mL (20 mg) three times a day for three days Additional increases may be necessary up to the maximum recommended dosage of 80 mg daily [4 mL (20 mg) four times a day]. 2.3 Administration Instructions Shake well FLEQSUVY oral suspension before administration. Discard unused portion 2 months after first opening. A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device. Nasogastric Tube Administration FLEQSUVY can be administered via a nasogastric (NG) tube at sizes 8 French or larger using the following steps: Ensure the NG feeding tube is flushed with appropriate amount of purified water (15 to 30 mL) prior to administration of FLEQSUVY. Draw the required dose of FLEQSUVY in the appropriate oral or enteral syringe and administer the dose via the feeding tube. The medication may remain in the dosing syringe for up to 4 hours prior to administration. If residual drug remains in the dosing syringe, draw up purified water into the syringe, shake gently, and administer through the feeding tube. Flush the feeding tube with at least 25 mL of purified water. 2.4 Discontinuation of FLEQSUVY When discontinuing FLEQSUVY, reduce the dosage slowly and avoid abrupt withdrawn from the drug to help minimize the risk of adverse reactions [see Warnings and Precautions ( 5.1 )] .

4 CONTRAINDICATIONS FLEQSUVY is contraindicated in patients with hypersensitivity to baclofen. Hypersensitivity to baclofen ( 4 )

5 WARNINGS AND PRECAUTIONS Abrupt discontinuation of baclofen has resulted in serious adverse reactions including death; therefore, reduce the dosage slowly when FLEQSUVY is discontinued. ( 5.1 ) Neonatal withdrawal symptoms can occur; gradually reduce the dosage and discontinue FLEQSUVY before delivery. ( 5.2 ) FLEQSUVY can cause drowsiness and sedation. Patients should avoid the operation of automobiles or other dangerous machinery until they know how the drug affects them. Advise patients that the central nervous system effects of FLEQSUVY may be additive to those of alcohol and other CNS depressants. ( 5.3 ) FLEQSUVY can cause exacerbation of the following: psychotic disorders, schizophrenia, or confusional states; autonomic dysreflexia; epilepsy. Use with caution in patients with these conditions. ( 5.5 , 5.6 , 5.7 ) 5.1 Adverse Reactions from Abrupt Withdrawal of FLEQSUVY Abrupt discontinuation of baclofen, regardless of the cause, has resulted in adverse reactions that include hallucinations, seizures, high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure, and death. Therefore, reduce the dosage slowly when FLEQSUVY is discontinued, unless the clinical situation justifies a rapid withdrawal. 5.2 Neonatal Withdrawal Symptoms Withdrawal symptoms in neonates whose mothers were treated with oral baclofen throughout pregnancy have been reported starting hours to days after delivery. The symptoms of withdrawal in these infants have included increased muscle tone, tremor, jitteriness, and seizure. If the potential benefit justifies the potential risk to the fetus and FLEQSUVY is continued during pregnancy, gradually reduce the dosage and discontinue FLEQSUVY before delivery. If slow withdrawal is not feasible, advise the parents or caregivers of the exposed neonate of the potential for neonatal withdrawal. 5.3 Drowsiness and Sedation Drowsiness and sedation have been reported in up to 63% of patients taking baclofen, the active ingredient in FLEQSUVY [see Adverse Reactions ( 6.1 )] . Patients should avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting FLEQSUVY or increasing the dose until they know how the drug affects them. Advise patients that the central nervous system depressant effects of FLEQSUVY may be additive to those of alcohol and other CNS depressants. 5.4 Poor Tolerability in Stroke Patients FLEQSUVY should be used with caution in patients who have had a stroke. Baclofen has not significantly benefited patients with stroke. These patients have also shown poor tolerability to the drug. 5.5 Exacerbation of Psychotic Disorders, Schizophrenia, or Confusional States FLEQSUVY should be used with caution in patients suffering from psychotic disorders, schizophrenia, or confusional states. If treated with FLEQSUVY, these patients should be kept under careful surveillance because exacerbations of these conditions have been observed with oral baclofen administration. 5.6 Exacerbation of Autonomic Dysreflexia FLEQSUVY should be used with caution in patients with a history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt withdrawal of FLEQSUVY may cause an autonomic dysreflexic episode. 5.7 Exacerbation of Epilepsy FLEQSUVY should be used with caution in patients with epilepsy. Deterioration in seizure control has been reported in patients taking baclofen. 5.8 Posture and Balance Effects FLEQSUVY should be used with caution in patients where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain increased function. 5.9 Ovarian Cysts A dose-related increase in incidence of ovarian cysts was observed in female rats treated chronically with oral baclofen. Ovarian cysts have been found by palpation in about 4% of the multiple sclerosis patients who were treated with oral baclofen for up to one year. In most cases, these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are estimated to occur spontaneously in approximately 1% to 5% of the normal female population.

7 DRUG INTERACTIONS 7.1 CNS Depressants and Alcohol FLEQSUVY can cause CNS depression, including drowsiness and sedation, which may be additive when used concomitantly with other CNS depressants or alcohol [see Warnings and Precautions ( 5.3 )] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Adverse Reactions from Abrupt Withdrawal of FLEQSUVY [see Warnings and Precautions ( 5.1 )] Neonatal Withdrawal Symptoms [see Warnings and Precautions ( 5.2 )] Drowsiness and Sedation [see Warnings and Precautions ( 5.3 )] Poor Tolerability in Stroke Patients [see Warnings and Precautions ( 5.4 )] Exacerbation of Psychotic Disorders, Schizophrenia, or Confusional States [see Warnings and Precautions ( 5.5 )] Exacerbation of Autonomic Dysreflexia [see Warnings and Precautions ( 5.6 )] Exacerbation of Epilepsy [see Warnings and Precautions ( 5.7 )] Posture and Balance Effects [see Warnings and Precautions ( 5.8 )] Ovarian Cysts [see Warnings and Precautions ( 5.9 )] The most common (up to 15% or more) adverse reactions in patients were drowsiness, dizziness, and weakness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reaction is transient drowsiness. In one controlled study of 175 patients, transient drowsiness was observed in 63% of those receiving baclofen compared to 36% of those in the placebo group. Other common adverse reactions (up to 15%) are dizziness and weakness. Adverse reactions with a frequency of ≥1% are listed in Table 1 . Table 1. Common (≥1%) Adverse Reactions in Patients Treated with Baclofen for Spasticity ADVERSE REACTION PERCENT Drowsiness 10-63% Dizziness 5-15% Weakness 5-15% Nausea 4-12% Confusion 1-11% Hypotension 0-9% Headache 4-8% Insomnia 2-7% Constipation 2-6% Urinary Frequency 2-6% Fatigue 2-4% The following adverse reactions not included in Table 1, classified by body system, were also reported: Neuropsychiatric: euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure Cardiovascular: dyspnea, palpitation, chest pain, syncope Gastrointestinal: dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stool Genitourinary: enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria Other: rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion The following laboratory tests have been found to be abnormal in patients receiving baclofen: increased SGOT, elevated alkaline phosphatase, and elevation of blood sugar.

8.1 Pregnancy Risk Summary There are no adequate data on the risk of major birth defects, miscarriages, or other maternal adverse outcomes associated with the use of FLEQSUVY in pregnant women. There are adverse effects on fetal outcomes associated with withdrawal from baclofen after delivery (see Clinical Considerations ) . Oral administration of baclofen to pregnant rats resulted in an increased incidence of fetal structural abnormalities at a dose that was also associated with maternal toxicity. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions FLEQSUVY may increase the risk of late-onset neonatal withdrawal symptoms [see Warnings and Precautions ( 5.2 )] . Data Animal Data Baclofen given orally has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses of rats given approximately 13 times on a mg/kg basis, or 3 times on a mg/m 2 basis, the maximum oral dose recommended for human use; this dose also caused reductions in food intake and weight gain in the dams. This abnormality was not seen in mice or rabbits.