, 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 ozobax 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 ozobax is continued during pregnancy, gradually reduce the dosage and discontinue ozobax 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 ozobax [see adverse reactions ( 6.1 )] . patients should avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting ozobax or increasing the dose until they know how the drug affects them. advise patients that the central nervous system depressant effects of ozobax may be additive to those of alcohol and other cns depressants. 5.4 poor tolerability in stroke patients ozobax 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 ozobax should be used with caution in patients suffering from psychotic disorders, schizophrenia, or confusional states. if treated with ozobax, 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 ozobax should be used with caution in patients with a history of autonomic dysreflexia. the presence of nociceptive stimuli or abrupt withdrawal of ozobax may cause an autonomic dysreflexic episode. 5.7 exacerbation of epilepsy ozobax 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 ozobax 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.

adverse reactions [see warnings and precautions ( 5.1 )].

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.

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 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 and any potential adverse effects on the breastfed infant from ozobax 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 should be given with caution to patients with renal impairment, and it may be necessary to reduce the dosage.

ioavailability for baclofen oral solution 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.

s ( 8.2 )]. increased risk of drowsiness with alcohol and other cns depressants advise patients that ozobax 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 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 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. storage instruct patients to store ozobax in the refrigerator [see how supplied/storage and handling ( 16.2 )]. manufactured by: entreprises importfab, inc. 50 hymus blvd. pointe-claire, qc, canada h9r 1c9 manufactured for: metacel pharmaceuticals, llc athens, ga 30601 ozobax ® is a registered u.s. trademark of metacel pharmaceuticals llc u.s. patent no. 10,610,502