Carisoprodol tablet

1 indications and usage

CARISOPRODOL is indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults.

Limitation of Use

CARISOPRODOL 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)].

CARISOPRODOL is a muscle relaxant indicated for the relief of discomfort associated withacute, painful musculoskeletal conditions in adults. (1)

Limitation of Use

Should only be used for acute treatment periods up to two or three weeks (1)

2 dosage and administration

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

  • Recommended dose is 350 mg three times a day and at bedtime. (2)

3 dosage forms and strengths

350 mg Tablets: White to off white, round convex tablets, debossed with CL above 022

Tablets: 350 mg (3)

4 contraindications

CARISOPRODOL is contraindicated in patients with a history of acute intermittent porphyria or a hypersensitivity reaction to a carbamate such as meprobamate.

  • Acute intermittent porphyria (4)
  • Hypersensitivity reactions to a carbamate such as meprobamate (4)

5 warnings and precautions

  • Due to sedative properties, may impair ability to perform hazardous tasks such as driving or operating machinery ( 5.1)
  • Additive sedative effects when used with other CNS depressants including alcohol ( 5.1)
  • Cases of abuse, dependence and withdrawal( 5.2, 9.2, 9.3)
  • Seizures ( 5.3)

5.1 sedation

CARISOPRODOL has sedative properties (in the low back pain trials, 13% to 17% of patients who received CARISOPRODOL experienced sedation compared to 6% of patients who received placebo) [see ADVERSE REACTIONS ( 6.1)] and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. There have been post-marketing reports of motor vehicle accidents associated with the use of CARISOPRODOL.

Since the sedative effects of CARISOPRODOL and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously.

5.2abuse, dependence, and withdrawal

Carisoprodol, the active ingredient in CARISOPRODOL, has been subject to abuse, dependence, and withdrawal, misuse and criminal diversion. [see Drug Abuse and Dependence ( 9.1, 9.2, 9.3)]. Abuse of CARISOPRODOL poses a risk of overdosage which may lead to death, CNS and respiratory depression, hypotension, seizures and other disorders [see Overdosage ( 10)].

Post-marketing experience cases of carisoprodol abuse and dependence have been reported in patients with prolonged use and a history of drug abuse. Although most of these patients took other drugs of abuse, some patients solely abused carisoprodol. Withdrawal symptoms have been reported following abrupt cessation of CARISOPRODOL after prolonged use. Reported withdrawal symptoms included insomnia, vomiting, abdominal cramps, headache, tremors, muscle twitching, ataxia, hallucinations, and psychosis. One of carisoprodols metabolites, meprobamate (a controlled substance), may also cause dependence [see Clinical Pharmacology ( 12.3)].

To reduce the risk of CARISOPRODOL abuse assess the risk of abuse prior to prescribing. After prescribing, limit the length of treatment to three weeks for the relief of acute musculoskeletal discomfort, keep careful prescription records, monitor for signs of abuse and overdose, and educate patients and their families about abuse and on proper storage and disposal.

5.3 seizures

There have been post-marketing reports of seizures in patients who received CARISOPRODOL. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) [see Overdosage ( 10)].

6 adverse reactions

Most common adverse reactions (incidence > 2%) are drowsiness, dizziness, and headache (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals NJ, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 clinical studies experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect rates observed in practice.

The data described below are based on 1387 patients pooled from two double blind, randomized, multicenter, placebo controlled, one-week trials in adult patients with acute, mechanical, lower back pain [see Clinical Studies ( 14)]. In these studies, patients were treated with 250 mg of CARISOPRODOL, 350 mg of CARISOPRODOL, or placebo three times a day and at bedtime for seven days. The mean age was about 41 years old with 54% females and 46% males and 74% Caucasian, 16% Black, 9% Asian, and 2% other.

There were no deaths and there were no serious adverse reactions in these two trials. In these two studies, 2.7%, 2%, and 5.4%, of patients treated with placebo, 250 mg of CARISOPRODOL, and 350 mg of CARISOPRODOL, respectively, discontinued due to adverse events; and 0.5%, 0.5%, and 1.8% of patients treated with placebo,250 mg of CARISOPRODOL, and 350 mg of CARISOPRODOL, respectively, discontinued due to central nervous system adverse reactions.

Table 1 displays adverse reactions reported with frequencies greater than 2% and more frequently than placebo in patients treated with CARISOPRODOL in the two trials described above.

Table 1. Patients with Adverse Reactions in Controlled Studies
AdverseReaction

Placebo

(n=560)

n (%)

CARISOPRODOL250 mg

(n=548)

n(%)

CARISOPRODOL350 mg

(n=279)

n (%)

Drowsiness 31 (6) 73 (13) 47 (17)
Dizziness 11 (2) 43 (8) 19 (7)
Headache 11 (2) 26 (5) 9 (3)

6.2 post-marketing experience

The following events have been reported during postapproval use of CARISOPRODOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular:Tachycardia, postural hypotension, and facial flushing [see Overdosage ( 10)].

Central Nervous System:Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures [see Overdosage ( 10)].

Gastrointestinal:Nausea, vomiting, and epigastric discomfort.

Hematologic:Leukopenia, pancytopenia.

7 drug interactions

CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) additive sedative effects ( 5.1, 7.1)

7.1 cns depressants

The sedative effects of CARISOPRODOL and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Concomitant use of CARISOPRODOL and meprobamate, a metabolite of CARISOPRODOL, is not recommended [see Warnings and Precautions ( 5.1)].

7.2 cyp2c19 inhibitors and inducers

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate [see Clinical Pharmacology ( 12.3)]. Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with CARISOPRODOL could result in increased exposure ofcarisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. Johns Wort, with CARISOPRODOL could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of CARISOPRODOL is unknown.

8 use in specific populations

8.1 pregnancy

Risk Summary

Data over many decades of carisoprodol use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Data on meprobamate, the primary metabolite of carisoprodol, also do not show a consistent association between maternal use of meprobamate and an increased risk of major birth defects (see Data).

In a published animal reproduction study, pregnant mice administered carisoprodol orally at 2.6- and 4.1-times the maximum recommended human dose ([MRHD] of 1400 mg per day [350 mg QID] based on body surface area [BSA] comparison) from gestation through weaning resulted in reduced fetal weights, postnatal weight gain, and postnatal survival (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Retrospective case-control and cohort studies of meprobamate use during the firsttrimester of pregnancy have not consistently identified an increased risk or pattern ofmajor birth defects. For children exposed to meprobamate in-utero, one study found noadverse effect on mental or motor development or IQ scores.

Animal Data

Embryofetal development studies in animals have not been completed.

In a published pre-and post-natal development animal study, pregnant miceadministered carisoprodol orally at 300, 750, or 1200 mg/kg/day (approximately1-, 2.6-, and 4.1-times the MRHD based on BSA comparison) from 7-days priorto gestation through birth and from lactation through weaning resulted in reducedfetal weights, postnatal weight gain, and postnatal survival at 2.6-and 4.1-timesthe MRHD.

8.2 lactation

Risk Summary

Data from published literature report that carisoprodol and its metabolite, meprobamate, are present in breastmilk. There are no data on the effect of carisoprodol on milk production. There is one report of sedation in an infant who was breastfed by a mother taking carisoprodol (see Clinical Considerations). Because there have been no consistent reports of adverse events in breastfed infants over decades of use, the developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for CARISOPRODOL and any potential adverse effects on the breastfed infant from CARISOPRODOL or from the underlying maternal condition.

Clinical Considerations

Infants exposed to CARISOPRODOL through breast milk should be monitored for sedation.

8.4 pediatric use

The efficacy, safety, and pharmacokinetics of CARISOPRODOL in pediatric patients less than 16 years of age have not been established.

8.5 geriatric use

The efficacy, safety, and pharmacokinetics of CARISOPRODOL in patients over 65 years old have not been established.

8.6 renal impairment

The safety and pharmacokinetics of CARISOPRODOL in patients with renal impairment have not been evaluated. Since CARISOPRODOL is excreted by the kidney, caution should be exercised if CARISOPRODOL is administered to patients with impaired renal function.Carisoprodol is dialyzable by hemodialysis and peritoneal dialysis.

8.7 hepatic impairment

The safety and pharmacokinetics of CARISOPRODOL in patients with hepatic impairment have not been evaluated. Since CARISOPRODOL is metabolized in the liver, caution should be exercised if CARISOPRODOL is administered to patients with impaired hepatic function.

8.8 patients with reduced cyp2c19 activity

Patients with reduced CYP2C19 activity have higher exposure to carisoprodol. Therefore, caution should be exercised in administration of CARISOPRODOL to these patients. [see Clinical Pharmacology ( 12.3)].

9 drug abuse and dependence

9.1 controlled substance

CARISOPRODOL contains carisoprodol, a Schedule IV controlled substance. Carisoprodolhas been subject to abuse, misuse, and criminal diversion for nontherapeutic use [see Warnings and Precautions ( 5.2)].

9.2 abuse

Abuse of carisoprodol poses a risk of overdosage which may lead to death, CNS andrespiratory depression, hypotension, seizures and other disorders [see Warnings andPrecautions ( 5.2) and Overdosage ( 10)]. Patients at high risk of CARISOPRODOL abusemay include those with prolonged use of carisoprodol, with a history of drug abuse, orthose who use CARISOPRODOL in combination with other abused drugs.

Prescription drug abuse is the intentional non-therapeutic use of a drug, even once, forits rewarding psychological effects. Drug addiction, which develops after repeated drugabuse, is characterized by a strong desire to take a drug despite harmful consequences,difficulty in controlling its use, giving a higher priority to drug use than to obligations,increased tolerance, and sometimes physical withdrawal. Drug abuse and drug addictionare separate and distinct from physical dependence and tolerance (for example, abuseor addiction may not be accompanied by tolerance or physical dependence) [see DrugAbuse and Dependence ( 9.3)].

9.3 dependence

Tolerance is when a patients reaction to a specific dosage and concentration isprogressively reduced in the absence of disease progression, requiring an increase inthe dosage to maintain the same. Physical dependence is characterized by withdrawalsymptoms after abrupt discontinuation or a significant dose reduction of a drug.Both tolerance and physical dependence have been reported with the prolonged use
of CARISOPRODOL. Reported withdrawal symptoms with CARISOPRODOL includeinsomnia, vomiting, abdominal cramps, headache, tremors, muscle twitching,anxiety, ataxia, hallucinations, and psychosis. Instruct patients taking large doses ofCARISOPRODOL or those taking the drug for a prolonged time to not abruptly stopCARISOPRODOL [see Warnings and Precautions ( 5.2)].

10 overdosage

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 hasbeen 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 ofcarisoprodol 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 presentationof the CARISOPRODOL overdose. Vomiting should not be induced because of the risk ofCNS and respiratory depression, and subsequent aspiration. Circulatory support should beadministered with volume infusion and vasopressor agents if needed. Seizures should betreated with intravenous benzodiazepines and the reoccurrence of seizures may be treatedwith phenobarbital. In cases of severe CNS depression, airway protective reflexes maybe compromised and tracheal intubation should be considered for airway protection andrespiratory support.

For decontamination in cases of severe toxicity, activated charcoal should be consideredin a hospital setting in patients with large overdoses who present early and are notdemonstrating 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

CARISOPRODOL Tablets are available as 350 mg round, white to off 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; 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 12H 24N 2 4, with amolecular weight of 260.33. The structural formula is:

Structure

Other ingredients in the CARISOPRODOL drug product include Hydroxypropyl cellulose, Lactose Anhydrous, Microcrystalline cellulose, Magnesium stearate, Pregelatinised starch, Sodium lauryl sulfate and Sodium starch glycolate.

12 clinical pharmacology

12.1 mechanism of action

The mechanism of action ofcarisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been clearly identified.

In animal studies, muscle relaxation induced bycarisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.

12.2 pharmacodynamics

Carisoprodolis a centrally acting skeletal muscle relaxant that does not directly relax skeletal muscles.

A metabolite of carisoprodol, meprobamate, has anxiolytic and sedative properties. The degree to which these properties of meprobamate contribute to the safety and efficacy of CARISOPRODOL is unknown.

12.3 pharmacokinetics

Absorption

The pharmacokinetics ofcarisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 250 mg and 350 mgCARISOPRODOL (see Table 2). The exposure ofcarisoprodol and meprobamate was dose proportional between the 250 mg and 350 mg doses. The C maxof meprobamate was 2.5 0.5 g/mL (mean SD) after administration of a single 350 mg dose ofCARISOPRODOL, which is approximately 30% of the C maxof meprobamate (approximately 8 g/mL) after administration of a single 400 mg dose of meprobamate.

Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean SD, n=24)

250 mg

CARISOPRODOL

350 mg

CARISOPRODOL

Carisoprodol
C max(g/mL) 1.2 0.5 1.8 1.0
AUC inf(g *hr/mL) 4.5 3.1 7.0 5.0
T max(hr) 1.5 0.8 1.7 0.8
T 1/2(hr) 1.7 0.5 2.0 0.5
Meprobamate
C max(g/mL) 1.8 0.3 2.5 0.5
AUC inf(g *hr/mL) 32 6.2 46 9.0
T max(hr) 3.6 1.7 4.5 1.9
T 1/2(hr) 9.7 1.7 9.6 1.5

Absolute bioavailability of carisoprodol has not been determined. The mean time to peakplasma concentrations (T max) of carisoprodol was approximately 1.5 to 2 hours.

Food Effect

Co-administration of a high-fat meal with CARISOPRODOL (350 mg tablet) had no effecton the pharmacokinetics of carisoprodol. Therefore, CARISOPRODOL may be administeredwith or without food.

Elimination

Metabolism:

The major pathway of carisoprodol metabolism is via the liver by cytochrome enzymeCYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patientswith Reduced CYP2C19 Activity below).

Excretion:

Carisoprodol is eliminated by both renal and non-renal routes with a terminal eliminationhalf-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.

Specific Populations

Sex

Exposure of carisoprodol is higher in female than in male subjects (approximately 30-50%on a weight adjusted basis). Overall exposure of meprobamate is comparable betweenfemale and male subjects.

Patients with Reduced CYP2C19 Activity

CARISOPRODOL should be used with caution in patients with reduced CYP2C19 activity.Published studies indicate that patients who are poor CYP2C19 metabolizers have a4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposureto meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poormetabolizers in Caucasians and African Americans is approximately 3-5% and in Asians
is approximately 15-20%.

13 nonclinical toxicology

13.1 carcinogenesis, mutagenesis, impairment of fertility

Carcinogenesis

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

Mutagenesis

CARISOPRODOL was not formally evaluated for genotoxicity. In published studies,carisoprodol was mutagenic in the in vitromouse 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 vitrochromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings.Carisoprodolwas not mutagenic in the Ames reverse mutation assay using S. typhimuriumstrains with or without metabolizing enzymes, and was not clastogenic in an in vivomouse micronucleus assay of circulating blood cells.

Impairment of Fertility

CARISOPRODOL was not formally evaluated for effects on fertility. A publishedreproductive study in which female mice received carisoprodol orally at doses of 300,750, or 1200 mg/kg/day (approximately 1, 2.6, and 4.1 times the MRHD of 1400 mg perday [350 mg QID] based on body surface area [BSA] comparison) from 1-week prior tomating, to 27-weeks post-mating found no alteration in fertility although an alteration
in reproductive cycles characterized by a greater time spent in estrus was observedat a carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did notdetermine fertility, mouse testes weight and sperm motility were reduced at a doseof 1200 mg/kg/day (maternal doses equivalent to 4.2-times the MRHD based on BSAcomparison). In both studies, the no effect level was 750 mg/kg/day, corresponding
to approximately 2.6-times the MRHD based on a BSA comparison. The significance ofthese findings for human fertility is not known.

14 clinical studies

The safety and efficacy ofCARISOPRODOL 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.

Table 3. Results of the Primary Efficacy Endpoints in Studies 1 and 2
Study Parameter Placebo CARISOPRODOL250 mg CARISOPRODOL350 mg
1 Number of Patients n=269 n=264 n=273
Relief from StartingBackache,Mean (SE) 1.4 (0.1) 1.8 (0.1) 1.8 (0.1)
Difference betweenCARISOPRODOL and Placebo,Mean (SE) (95% CI)

0.4

(0.2, 0.5)

0.4

(0.2, 0.6)

Global Impression ofChange, Mean (SE) 1.9 (0.1) 2.2 (0.1) 2.2 (0.1)
Difference betweenCARISOPRODOL and Placebo,Mean (SE) (95% CI)

0.2

(0.1, 0.4)

0.3

(0.1, 0.4)

2 Number of Patients n=278 n=269
Relief from StartingBackache, Mean (SE) 1.1 (0.1) 1.8 (0.1)
Difference betweenCARISOPRODOL and Placebo,Mean (SE) (95% CI)

0.7

(0.5, 0.9)

Global Impression ofChange, Mean (SE) 1.7 (0.1) 2.2 (0.1)
Difference betweenCARISOPRODOL and Placebo,Mean (SE) (95% CI)

0.5

(0.4, 0.7)

Patients treated withCARISOPRODOL 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

350 mg Tablets: White to off white, Round convex tablets, debossed with CL: above 022 on one side available in:

Bottles of 100 NDC 64980-174-01.

Bottles of 500 NDC 64980-174-05.

Bottles of 1000 NDC 64980-174-10.

Storage and handling section

Storage:Store at Controlled room temperature 20 to 25C (68 to 77F).[See USP Controlled Room Temperature]

17 patient counseling information

Patients should be advised to contact their physician if they experience any adversereactions to CARISOPRODOL.

Sedation

Advise patients that CARISOPRODOL may cause drowsiness and/or dizziness, and hasbeen associated with motor vehicle accidents. Patients should be advised to avoidtaking CARISOPRODOL before engaging in potentially hazardous activities such asdriving 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 checkwith their doctor before taking other CNS depressants such as benzodiazepines, opioids,tricyclic antidepressants, sedating antihistamines, or other sedatives [see Warnings andPrecautions ( 5.1)].

CARISOPRODOL Should Only Be Used for Short-Term Treatment

Advise patients that treatment with CARISOPRODOL should be limited to acute use (upto two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketingexperience with CARISOPRODOL, cases of dependence, withdrawal, andabuse have been reported with prolonged use. If the musculoskeletal symptoms stillpersist, 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)].

Manufactured for:
Rising Pharmaceuticals, Inc.
Allendale, NJ 07401

Manufactured by:
lngenus Pharmaceuticals NJ, LLC
Fairfield, NJ 07004

Rx Only

550601 Rev. 10/18

Ingredients and appearance - Product information

Carisoprodol tablet- Carisoprodol

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 64980-174
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Carisoprodol ( UNII: 21925K482H)( Carisoprodol - UNII: 21925K482H ) 350 mgin 1

Inactive Ingredients

Ingredient Name Code
Hydroxypropyl cellulose ( UNII: RFW2ET671P)
Anhydrous lactose ( UNII: 3SY5LH9PMK)
Cellulose, microcrystalline ( UNII: OP1R32D61U)
Magnesium stearate ( UNII: 70097M6I30)
Starch, corn ( UNII: O8232NY3SJ)
Sodium lauryl sulfate ( UNII: 368GB5141J)
Sodium starch glycolate type a potato ( UNII: 5856J3G2A2)

Product Characteristics

Color WHITE Score 1
Shape ROUND Size 5 mm
Imprint Code CL;022

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA040823 USA

Labeler - Rising Pharmaceuticals, Inc.( 041241766)

Establishment

Name ID/FEI Business Operations
Rising Pharmaceuticals, Inc. 041241766 manufacture( 64980-174)

Package label.principal display panel

Package Label - Principal Display Panel 100-count Bottle

Rising NDC 64980-174-01

Carisoprodol
Tablets, USP

350 mg

100 Tablets Rx only

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 O (worst outcome) to 4 (best outcome).
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.