OZOBAX DS

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Adverse Reactions from Abrupt Withdrawal of OZOBAX DS [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 Metacel Pharmaceuticals, LLC at 1-833-469-6229 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.

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

11 DESCRIPTION OZOBAX DS (baclofen) oral solution is a gamma-aminobutyric acid (GABA-ergic) agonist available as 10 mg/5 mL solution for oral administration. Its chemical name is 4-amino-3-(4-chlorophenyl)-butanoic acid, and its structural formula is: Molecular formula is C 1O H 12 CINO 2 . Molecular Weight is 213.66. Baclofen USP is a white to off-white, odorless or practically odorless crystalline powder. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform. The OZOBAX DS (baclofen) oral solution inactive ingredients are: glycerin, methylparaben, propylparaben, purified water, and sucralose. May also contain sodium hydroxide or hydrochloric acid for pH adjustment. bac structure

2 DOSAGE AND ADMINISTRATION Baclofen oral solution is available in multiple concentrations; include both the total dose in mg and the total dose in volume on prescriptions ( 2.1 ) Initiate OZOBAX DS 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 Dosage Information Baclofen oral solution is available in multiple concentrations; ensure accuracy when prescribing, dispensing and administering baclofen oral solution to avoid dosing errors due to confusion between mg and mL, and with other baclofen oral solutions of different concentrations. When writing prescriptions, include both the total dose in mg and the total dose in volume. 2.2 Recommended Dosage Initiate OZOBAX DS 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: 5 mg (2.5 mL) three times a day for three days 10 mg (5 mL) three times a day for three days 15 mg (7.5 mL) three times a day for three days 20 mg (10 mL) three times a day for three days Additional increases may be necessary up to the maximum recommended dosage of 80 mg daily (20 mg four times a day). 2.3 Discontinuation of OZOBAX DS When discontinuing OZOBAX DS, 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 )].

1 INDICATIONS AND USAGE OZOBAX DS 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. OZOBAX DS may also be of some value in patients with spinal cord injuries and other spinal cord diseases. Limitations of Use OZOBAX DS is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders. OZOBAX DS 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 ) OZOBAX DS may also be of some value in patients with spinal cord injuries and other spinal cord diseases. ( 1 ) Limitations of Use OZOBAX DS is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders ( 1 )

10 OVERDOSAGE 10.1 Symptoms of Baclofen Overdose Patients may present in coma or with progressive drowsiness, lightheadedness, dizziness, somnolence, accommodation disorders, respiratory depression, seizures, or hypotonia progressing to loss of consciousness. 10.2 Treatment for Overdose The treatment of baclofen overdose includes gastric decontamination, maintaining an adequate airway and respirations.

7 DRUG INTERACTIONS 7.1 CNS Depressants and Alcohol OZOBAX DS 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 )].

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The precise mechanism of action of baclofen is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), and may exert its effects by stimulation of the GABA B receptor subtype. 12.2 Pharmacodynamics Baclofen has been shown to have general CNS depressant properties, as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 ), and Overdosage ( 10.1 )]. 12.3 Pharmacokinetics A pharmacokinetic study in heathy adult male subjects under fasting conditions at 20 mg dose level demonstrated similar bioavailability for baclofen oral solution (5 mg/5 mL) and oral tablets. The peak plasma concentrations were achieved in about 0.75 hours from oral solution and the apparent elimination half-life is about 5.7 hours. Baclofen is excreted primarily by the kidney in unchanged form, and there is relatively large intersubject variation in absorption and/or elimination.

20231017

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3 DOSAGE FORMS AND STRENGTHS Oral Solution: 10 mg/5 mL baclofen as a clear, colorless solution Oral Solution: 10 mg/5 mL ( 3 )

OZOBAX DS Baclofen GLYCERIN METHYLPARABEN PROPYLPARABEN SUCRALOSE WATER BACLOFEN BACLOFEN

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No increase in tumors was seen in rats receiving baclofen orally for two years at approximately 30 to 60 times on a mg/kg basis, or 10 to 20 times on a mg/ m 2 basis, the maximum oral dose recommended for human use. Mutagenesis Genetic toxicology assays have not been conducted for baclofen. Impairment of Fertility Studies to evaluate the effects of baclofen on fertility have not been conducted.

NDA208193

OZOBAX DS

Baclofen

69528-302

HUMAN PRESCRIPTION DRUG

ORAL

PACKAGE LABEL. PRINCIPAL DISPLAY PANEL NDC 69528-302-08 OZOBAX ® DS (baclofen) Oral Solution 10 mg / 5 mL (2 mg/mL) Baclofen oral solution is available in different concentrations Clear liqud solution R X only 8 fl. oz. (237 mL) NDC 69528-302-16 OZOBAX ® DS (baclofen) Oral Solution 10 mg / 5 mL (2 mg/mL) Baclofen oral solution is available in different concentrations Clear liqud solution R X only 16 fl. oz. (473 mL) 302-08 302-16

17 PATIENT COUNSELING INFORMATION Administration Instructions Instruct patients or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform patients that oral dosing syringes may be obtained from their pharmacy. Risks Related to Sudden Withdrawal of OZOBAX DS Advise patients and caregivers not to discontinue use of OZOBAX DS without consulting with their healthcare provider because sudden withdrawal of OZOBAX DS can result in serious complications that include hallucinations, seizures, high fever, confusion, muscle stiffness, multiple organ-system failure, and death [see Warnings and Precautions ( 5.1 )]. Inform patients that early symptoms of OZOBAX DS withdrawal may include increased spasticity, itching, and tingling of extremities. Neonatal Withdrawal Symptoms Advise patients to notify their healthcare provider if they are pregnant, plan to become pregnant, or plan to breastfeed [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.2 )]. Increased Risk of Drowsiness with Alcohol and Other CNS Depressants Advise patients that OZOBAX DS may cause drowsiness, and that they should avoid the operation of automobiles or other dangerous machinery, or activities made hazardous by decreased alertness when starting OZOBAX DS or increasing the dose until they know how the drug affects them [see Warnings and Precautions ( 5.3 )]. Inform patients and their caregivers that the drowsiness associated with OZOBAX DS use can be worsened by alcohol and other CNS depressants. Advise patients to read all medicine labels carefully, and to tell their healthcare provider about all prescription and nonprescription drugs they may use. Manufactured by: Delpharm Montreal, Inc. 3535 Route Trans Canada Highway Pointe-Claire, QC, Canada H9R 1B4 Manufactured for: Metacel Pharmaceuticals, LLC Athens, GA 30601 OZOBAX ® is a registered U.S. trademark of Metacel Pharmaceuticals LLC

14 CLINICAL STUDIES The efficacy of OZOBAX DS is based upon a bioavailability study in healthy adults comparing baclofen oral tablets to baclofen oral solution [see Clinical Pharmacology ( 12.3 )].

8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) Because baclofen is excreted unchanged through the kidneys it may be necessary to reduce the dosage in patients with impaired renal function. ( 8.6 ) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of OZOBAX DS in pregnant women. Oral administration of baclofen to pregnant rats resulted in an increased incidence of fetal structural abnormalities at a dose which 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 Ozobax DS 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. 8.2 Lactation Risk Summary At recommended oral doses, baclofen is present in human milk. There are no human data on the effects of baclofen on milk production. There are no adequate data on the effects of baclofen on the breastfed infant. Withdrawal symptoms can occur in breastfed infants when maternal administration of OZOBAX DS is stopped, or when breastfeeding is stopped [see Warnings and Precautions ( 5.2 )] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OZOBAX DS and any potential adverse effects on the breastfed infant from OZOBAX DS or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 have not been established. 8.5 Geriatric Use In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 8.6 Renal Impairment Because baclofen is primarily excreted unchanged through the kidneys, OZOBAX DS should be given with caution to patients with renal impairment, and it may be necessary to reduce the dosage.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied OZOBAX DS (baclofen) Oral Solution contains 10 mg/5 mL baclofen. It is a clear, colorless solution and is supplied in bottles of 237 mL (NDC 69528-302-08) and 473 mL (NDC 69528-302-16). 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure.