Baclofen

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

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 baclofen oral solution 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 baclofen oral solution 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 Baclofen Oral Solution When discontinuing baclofen oral solution, 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 )].

3 DOSAGE FORMS AND STRENGTHS Oral Solution: 5 mg/5 mL baclofen,USP as a clear, colorless solution with a grape flavor. Oral Solution: 5 mg/5 mL ( 3 )

4 CONTRAINDICATIONS Baclofen oral solution is contraindicated in patients with hypersensitivity to baclofen. Hypersensitivity to baclofen ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Adverse Reactions from Abrupt Withdrawal of Baclofen Oral Solution [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 Palmetto Pharmaceuticals Inc. at 1-844-627-7696 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 DRUG INTERACTIONS 7.1 CNS Depressants and Alcohol Baclofen oral solution 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)].

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

11 DESCRIPTION Baclofen is a gamma-aminobutyric acid (GABA-ergic) agonist available as 5 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 10 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 inactive ingredients of baclofen oral solution are: carboxymethyl cellulose sodium, glycerin, grape flavor NAT & ART, methylparaben, propylparaben, purified water, and sucralose. May also contain sodium hydroxide or hydrochloric acid for pH adjustment. image description

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.

16 HOW SUPPLIED/STORAGE AND HANDLING Baclofen Oral Solution contains 10 mg/5 mL baclofen. It is a clear, colorless solution. UD Cups - 17856-0620-01 - 2.5 ML 72 ct 17856-0620-02 - 5 ML 72 ct UD Syringes - 17856-0620-03 2.5 ML Enfit 1 ct 17856-0620-09 2.5 ML Enfit 90 ct 17856-0620-04 5 ML Enfit 1 ct 17856-0620-05 5 mL Enfit 45 ct 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.