carisoprodol

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

Carisoprodol tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. Limitation of Use Carisoprodol tablets should only be used for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use has not been established and because acute, painful musculoskeletal conditions are generally of short duration [see Dosage and Administration (2) ].

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

The recommended dose of carisoprodol tablets is 250 mg to 350 mg three times a day and at bedtime. The recommended maximum duration of carisoprodol tablets use is up to two or three weeks.

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Carisoprodol tablets USP, 250 mg are white colored, round shaped, biconvex, uncoated tablets, identified with ‘H 94’ debossed on one side and other side plain. Carisoprodol tablets USP, 350 mg are white colored, round shaped, biconvex, uncoated tablets, identified with ‘D’ debossed on one side and ‘31’ on the other side.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Carisoprodol tablets are contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

9 DRUG ABUSE AND DEPENDENCE

DRUG ABUSE AND DEPENDENCE SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

Clinical Presentation Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with carisoprodol overdosage. Serotonin syndrome has been reported with carisoprodol intoxication. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants. Treatment of Overdosage Basic life support measures should be instituted as dictated by the clinical presentation of the carisoprodol overdose. Vomiting should not be induced because of the risk of CNS and respiratory depression, and subsequent aspiration. Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support. For decontamination in cases of severe toxicity, activated charcoal should be considered in a hospital setting in patients with large overdoses who present early and are not demonstrating CNS depression and can protect their airway. For more information on the management of an overdose of carisoprodol, contact a Poison Control Center.

11 DESCRIPTION

DESCRIPTION SECTION

Carisoprodol tablets, USP are available as 250 mg and 350 mg round, white tablets. Carisoprodol USP is a white, crystalline powder, having a mild, characteristic odor and a bitter taste. It is slightly soluble in water; freely soluble in alcohol, in chloroform, and in acetone; and its solubility is practically independent of pH. Carisoprodol is present as a racemic mixture. Chemically, carisoprodol is (±)-2-Methyl-2-propyl-1,3-propanediol carbamate isopropylcarbamate and the molecular formula is C 12 H 24 N 2 O 4 , with a molecular weight of 260.33. The structural formula is: Other ingredients in the carisoprodol tablets, USP include pregelatinized starch (maize), crospovidone, povidone, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

The safety and efficacy of carisoprodol for the relief of acute, idiopathic mechanical low back pain was evaluated in two, 7-day, double blind, randomized, multicenter, placebo controlled, U.S. trials (Studies 1 and 2). Patients had to be 18 to 65 years old and had to have acute back pain (≤ 3 days of duration) to be included in the trials. Patients with chronic back pain; at increased risk for vertebral fracture (e.g., history of osteoporosis); with a history of spinal pathology (e.g., herniated nucleus pulposus, spondylolisthesis or spinal stenosis); with inflammatory back pain, or with evidence of a neurologic deficit were excluded from participation. Concomitant use of analgesics (e.g., acetaminophen, NSAIDs, tramadol, opioid agonists), other muscle relaxants, botulinum toxin, sedatives (e.g., barbiturates, benzodiazepines, promethazine hydrochloride), and anti-epileptic drugs was prohibited. In Study 1, patients were randomized to one of three treatment groups (i.e., carisoprodol 250 mg, carisoprodol 350 mg, or placebo) and in Study 2 patients were randomized to two treatment groups (i.e., carisoprodol 250 mg or placebo). In both studies, patients received study medication three times a day and at bedtime for seven days. The primary endpoints were the relief from starting backache and the global impression of change, as reported by patients, on Study Day 3. Both endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome) in both studies. The primary statistical comparison was between the carisoprodol 250 mg and placebo groups in both studies. The proportion of patients who used concomitant acetaminophen, NSAIDs, tramadol, opioid agonists, other muscle relaxants, and benzodiazepines was similar in the treatment groups. The results for the primary efficacy evaluations in the acute, low back pain studies are presented in Table 3. a The primary efficacy endpoints (Relief from Starting Backache and Global Impression of Change) were assessed by the patients on Study Day 3. These endpoints were scored on a 5-point rating scale from 0 (worst outcome) to 4 (best outcome). b Mean is the least squared mean and SE is the standard error of the mean. The ANOVA model was used for the primary statistical comparison between the carisoprodol 250 mg and placebo groups. Table 3. Results of the Primary Efficacy Endpoints a in Studies 1 and 2 Study Parameter Placebo Carisoprodol 250 mg Carisoprodol 350 mg 1 Number of Patients n=269 n=264 n=273 Relief from Starting Backache, Mean (SE) b 1.4 (0.1) 1.8 (0.1) 1.8 (0.1) Difference between Carisoprodol and Placebo, Mean (SE) b (95% CI) 0.4 (0.2, 0.5) 0.4 (0.2, 0.6) Global Impression of Change, Mean (SE) b 1.9 (0.1) 2.2 (0.1) 2.2 (0.1) Difference between Carisoprodol and Placebo, Mean (SE) b (95% CI) 0.2 (0.1, 0.4) 0.3 (0.1, 0.4) 2 Number of Patients n=278 n=269 Relief from Starting Backache, Mean (SE) b 1.1 (0.1) 1.8 (0.1) Difference between Carisoprodol and Placebo, Mean (SE) b (95% CI) 0.7 (0.5, 0.9) Global Impression of Change, Mean (SE) b 1.7 (0.1) 2.2 (0.1) Difference between Carisoprodol and Placebo, Mean (SE) b (95% CI) 0.5 (0.4, 0.7) Patients treated with carisoprodol experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Carisoprodol Tablets USP, 350 mg are white colored, round shaped, biconvex, uncoated tablets, identified with ‘D’ debossed on one side and ‘31’ on the other side. Bottles of 60 NDC 68071-3421-6 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in tight container.

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Patients should be advised to contact their physician if they experience any adverse reactions to carisoprodol. Sedation Advise patients that carisoprodol may cause drowsiness and/or dizziness, and has been associated with motor vehicle accidents. Patients should be advised to avoid taking carisoprodol before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [see Warnings and Precautions (5.1) ]. Avoidance of Alcohol and Other CNS Depressants Advise patients to avoid alcoholic beverages while taking carisoprodol and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives [see Warnings and Precautions (5.1)] . Carisoprodol Should Only Be Used for Short-Term Treatment Advise patients that treatment with carisoprodol should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. If the musculoskeletal symptoms still persist, patients should contact their healthcare provider for further evaluation. Lactation Advise nursing mothers using carisoprodol to monitor neonates for signs of sedation [see Use in Specific Populations (8.2) ]. Distributed by: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Made in India Code: TS/DRUGS/19/1993 Issued: 06/2021

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL