Carisoprodol (Page 3 of 4)

13 NON CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed to evaluate the carcinogenic potential of carisoprodol.

Carisoprodol Tablets were not formally evaluated for genotoxicity. In published studies, carisoprodol was mutagenic in the in vitro mouse lymphoma cell assay in the absence of metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes. Carisoprodol was clastogenic in the in vitro chromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings. Carisoprodol was not mutagenic in the Ames reverse mutation assay using S. typhimurium strains with or without metabolizing enzymes, and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.

Carisoprodol was not formally evaluated for effects on fertility. Published reproductive studies of carisoprodol in mice found no alteration in fertility although an alteration in reproductive cycles characterized by a greater time spent in estrus was observed at a carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day. In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6 times the human equivalent dosage of 350 mg four times a day, based on a body surface area comparison. The significance of these findings for human fertility is not known.

14 CLINICAL STUDIES

The safety and efficacy of Carisoprodol Tablets for the relief of acute, idiopathic mechanical low back pain was evaluated in one, 7-day, double blind, randomized, multicenter, placebo controlled, U.S. trials (Study 1). 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 pulposis, 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 Tablets 350 mg, or placebo). In the study 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.

Table 3. Results of the Primary Efficacy Endpoints* in Study 1

Study Parameter Placebo

Carisoprodol Tablets 350 mg

1 Number of Patients n=269 n=273
Relief for Starting Backache, Mean (SE) 1.4(0.1) 1.8 (0.1)
Difference between Carisoprodol and Placebo, Mean (SE)† (95% CI) 0.4
(0.2, 0.6)
Global Impression of Change, Mean (SE)† 1.9(0.1) 2.2 (0.1)
Difference between Carisoprodol and Placebo, Mean (SE)† (95% CI)

0.3
(0.1, 0.4)

*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).

†Mean is the least squared mean and SE is the standard error of the mean.

Patients treated with Carisoprodol Tablets experienced improvement in function as measured by the Roland-Morris Disability Questionnaire (RMDQ) score on Days 3 and 7.

16 HOW SUPPLIED

Carisoprodol Tablets, USP 350 mg, are white, round, unscored tablets; imprinted “WW 176”, are available in:

Bottles of 100 tablets
Bottles of 500 tablets
Bottles of 1000 tablets

Store at 20-25 o C (68-77 o F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

17 PATIENT COUNSELING INFORMATION

Patients should be advised to contact their physician if they experience any adverse reactions to Carisoprodol Tablets.

17.1 Sedation

Patients should be advised that Carisoprodol Tablets may cause drowsiness and/or dizziness, and have been associated with motor vehicle accidents. Patients should be advised to avoid taking Carisoprodol Tablets before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [see Warnings and Precautions (5.1)]

17.2 Avoidance and Alcohol and Other CNS Depressants

Patients should be advised to avoid alcoholic beverages while taking Carisoprodol Tablets 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)].

17.3 Carisoprodol Tablets Should Only be Used for Short-Term Treatment

Patients should be advised that treatment with Carisoprodol Tablets 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 Tablets, 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.

Manufactured for:
West-ward Pharmaceutical Corp
Eatontown, NJ 07724

Manufactured by:
Shasun Chemical and Drugs Ltd.
Pondicherry, India

Revised August 2010 020000823

11 DESCRIPTION

Carisoprodol Tablets are available as 350 mg round, white tablets. Carisoprodol 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; its solubility is practically independent of pH. Carisoprodol is present as a racemic mixture. Chemically, carisioprodol is N-isopropyl-2-methyl-2-propyl-1,3- propanediol dicarbamate and the molecular formula is C 12 H 24 N 2 O 4 , with a molecular weight of 260.33. The structural formula is:

Structure

Other Ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, methylcellulose, povidone, sodium lauryl sulfate, sodium starch glycolate, and stearic acid.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2021. All Rights Reserved.