allucinations, 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 lyvispah 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 lyvispah is continued during pregnancy, gradually reduce the dosage, and discontinue lyvispah 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 lyvispah [see adverse reactions ( 6.1 )]. patients should avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting lyvispah or increasing the dosage until they know how the drug affects them. advise patients that the central nervous system depressant effects of lyvispah may be an additive to those of alcohol and other cns depressants. 5.4 poor tolerability in stroke patients lyvispah 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 lyvispah should be used with caution in patients suffering from psychotic disorders, schizophrenia, or confusional states. if treated with lyvispah, 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 lyvispah should be used with caution in patients with a history of autonomic dysreflexia. the presence of nociceptive stimuli or abrupt withdrawal of lyvispah may cause an autonomic dysreflexic episode. 5.7 exacerbation of epilepsy lyvispah 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 lyvispah 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 continue to receive the drug. ovarian cysts are estimated to occur spontaneously in approximately 1% to 5% of the normal female population.

sage of 80 mg daily (20 mg four times a day). multiple packets or multiple strengths can be used to achieve the prescribed dosage. 2.2 administration instructions the entire contents of the packet should be emptied into the mouth. the granules will dissolve in the mouth or can be swallowed. lyvispah can be taken with liquids or soft foods if needed. administration with liquids or soft foods lyvispah can be administered orally as a mixture with liquids or soft foods, such as apple sauce, yogurt, or pudding. the contents of one packet can be emptied and mixed with up to 15 ml of liquid or soft food. the mixture should be administered no more than 2 hours after mixing. if multiple packets are to be administered, each packet must be mixed with a separate volume of liquid or soft food. dministration via feeding tube lyvispah can also be administered via enteral feeding tubes such as nasogastric (ng) at sizes 8 fr or higher, gastrostomy (g) at sizes 12 fr or higher, percutaneous endoscopic gastrostomy (peg) at sizes 14 fr or higher, and gastrojejunostomy (gj) tubes at sizes 16 fr or higher. flush the feeding tube with up to 15 ml of water using a catheter tip syringe. open and empty the full contents of one packet of lyvispah in 15 ml of liquid, such as apple juice or milk, in a clean container. mix the suspension to ensure all granules are wetted. draw up the suspension of granules into a dosing syringe immediately after mixing and administer the dose via the feeding tube. administration should be no longer than two hours after mixing. if the syringe is allowed to stand for 15 minutes before administration, invert the syringe three times. refill the dosing syringe with 15 ml of water and flush the feeding tube. if multiple packets are to be administered, each packet must be mixed with a separate volume of liquid. 2.3 discontinuation of lyvispah when discontinuing lyvispah, reduce the dosage slowly and avoid abrupt withdrawal from the drug to help minimize the risk of adverse reactions [see warnings and precautions ( 5.1 )].

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.

0%, respectively. clinical considerations fetal/neonatal adverse reactions lyvispah 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 effects of baclofen on milk production. withdrawal symptoms can occur in breastfed infants when maternal administration of lyvispah is stopped, or when breastfeeding is stopped [see warnings and precautions (5.2) ] . there are no adequate data on other effects of baclofen on the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lyvispah and any potential adverse effects on the breastfed infant from lyvispah 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. this drug 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 [see use in specific populations (8.6) ] . 8.6 renal impairment because baclofen is primarily excreted unchanged through the kidneys, lyvispah should be given with caution to patients with renal impairment, and it may be necessary to reduce the dosage.

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.

ilability for baclofen oral granules and oral tablets. absorption the peak plasma concentrations of baclofen oral granule formulation were achieved in about one hour and the apparent elimination half-life is about 5.5 hours. the exposure of baclofen was dose proportional across the dose range of 5 mg, 10 mg, and 20 mg. effect of food administering lyvispah with or without water, or with applesauce did not affect the bioavailability of baclofen oral granules. administration with a high fat meal resulted in 10% decrease in auc and 29% decrease in c max compared to the fasted state. elimination baclofen is excreted primarily by the kidney in unchanged form, and there is relatively large intersubject variation in absorption and/or elimination.

s lyvispah can be administered via enteral feeding tubes, such a nasogastric (ng), gastrostomy (g), percutaneous endoscopic gastrostomy (peg), and gastrojejunostomy (gj) tubes. flush the feeding tube with up to 15 ml (one tablespoonful) of water. open and empty the full contents of one packet of lyvispah in 15 ml (one tablespoonful) of the preferred liquid. stir the suspension to ensure all granules are wetted. draw up the suspension of granules into a dosing syringe immediately after stirring and administer the dose via the feeding tube. administer no longer than two hours after mixing. refill the dosing syringe with 15 ml (one tablespoonful) of water and flush the feeding tube with the remaining contents. any unused suspensions should be discarded. risks related to sudden withdrawal of lyvispah advise patients and caregivers not to discontinue use of lyvispah without consulting with their healthcare provider because sudden withdrawal of lyvispah 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 lyvispah 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 lyvispah 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 lyvispah or increasing the dose of lyvispah until they know how the drug affects them [see warnings and precautions (5.3) ] . inform patients and their caregivers that the drowsiness associated with lyvispah 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. distributed by: saol therapeutics, inc. roswell, ga 30076