LYVISPAH

LYVISPAH (baclofen) oral granules is a gamma-aminobutyric acid (GABA-ergic) agonist available as 5 mg, 10 mg, or 20 mg of baclofen oral granules in a packet. Its chemical name is 4-amino-3-(4- chlorophenyl)-butanoic acid and its structural formula is: Molecular formula is C10H12ClNO2 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. LYVISPAH (baclofen) oral granules inactive ingredients include amino methacrylate copolymer, calcium stearate, colloidal silicon dioxide, crospovidone, hypromellose, mannitol, saccharin sodium, strawberry flavor, talc, and xylitol. chem structure

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

Initiate LYVISPAH with a low dosage, preferably in divided doses, administered orally. Increase gradually based on clinical response and tolerability. ( 2.1 ) The maximum dosage is 80 mg daily (20 mg four times a day). ( 2.1 ) LYVISPAH can be taken with or without water. ( 2.2 ) LYVISPAH oral granules can be mixed with soft food for administration within 2 hours. ( 2.2 ) LYVISPAH oral granules can be administered via enteral feeding tubes. ( 2.2 ) When discontinuing, reduce the dose slowly. ( 2.2 ) 2.1 Recommended Dosage Initiate LYVISPAH 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 three times a day for three days 10 mg three times a day for three days 15 mg three times a day for three days 20 mg 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). 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. Administration 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) ] .

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

The following clinically significant adverse reactions are described elsewhere in the labeling: Adverse Reactions from Abrupt Withdrawal of LYVISPAH [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 adverse reactions (up to 15% or more) in patients were drowsiness, dizziness, and weakness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 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.

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