CARISOPRODOL  - carisoprodol tablet 
Lake Erie Medical DBA Quality Care Products LLC

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CARISOPRODOL 350 mg



12 24 2 4


12 CLINICAL PHARMACOLOGY



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

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



Carisoprodol is 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.

The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg carisoprodol (see Table 2). The Cmax of meprobamate was 2.5 ± 0.5 μg/mL (mean ± SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the Cmax of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.

Table 2. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)
   350 mg Carisoprodol
   Carisoprodol
 Cmax (μg/mL)  1.8 ± 1.0
 AUCinf (μg*hr/mL)  7.0 ± 5.0
 Tmax (hr)  1.7 ± 0.8
 T½ (hr)  2.0 ± 0.5
   Meprobamate
 Cmax (μg/mL)  2.5 ± 0.5
 AUCinf (μg*hr/mL)  46 ± 9.0
 Tmax (hr)  4.5 ± 1.9
 T½ (hr)  9.6 ± 1.5
Absorption: max

Metabolism:

Elimination:

Gender:

Patients with Reduced CYP2C19 Activity:







in vitro in vitro S. typhimurium in vivo






1 INDICATIONS AND USAGE

Carisoprodol Tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults.

  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)].

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







see Clinical Studies (14)





Table 1. Patients with Adverse Reactions in the Controlled Study
 Adverse
Reaction
 Placebo
(n=560)
n (%)
 Carisoprodol 350 mg
(n=279)
n (%)
 Drowsiness  31 (6)  47 (17)
 Dizziness  11 (2)  19 (7)
 Headache  11 (2)  9 (3)

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.






Treatment of Overdosage:

contact a Poison Control Center

2 DOSAGE AND ADMINISTRATION

The recommended dose of Carisoprodol Tablets, USP is 350 mg three times a day and at bedtime. The recommended maximum duration of Carisoprodol Tablets, USP use is up to two or three weeks.

350 mg Tablets: white, round, unscored tablets debossed "2410 V" on one side and plain on the reverse side; available in bottles of 100, 500 and 1000.

Storage:
Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Patients should be advised to contact their physician if they experience any adverse reactions to carisoprodol tablets.

Since carisoprodol tablets may cause drowsiness and/or dizziness, patients should be advised to assess their individual response to carisoprodol tablets before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery [see Warnings and Precautions (5.1)].

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)].

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. If symptoms still persist, patients should contact their healthcare provider for further evaluation.

Manufactured for:
QUALITEST PHARMACEUTICALS
Huntsville, AL 35811

8181281
Revised 2/2009
R4


The efficacy of the maximum recommended dose of LYRICA for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies with three times a day dosing, two of which studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for 1 to 5 years. A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a minimum mean baseline pain score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.1 to 6.7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study DPN 1: This 5-week study compared LYRICA 25, 100, or 200 mg three times a day with placebo. Treatment with LYRICA 100 and 200 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. There was no evidence of a greater effect on pain scores of the 200 mg three times a day dose than the 100 mg three times a day dose, but there was evidence of dose dependent adverse reactions [see Adverse Reactions (6.1)]. For a range of degrees of improvement in pain from baseline to study endpoint, Figure 1 shows the fraction of patients achieving that degree of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

The efficacy of LYRICA for the management of postherpetic neuralgia was established in three double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum baseline score of ≥4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). Seventy-three percent of patients completed the studies. The baseline mean pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study PHN 1: This 13-week study compared LYRICA 75, 150, and 300 mg twice daily with placebo. Patients with creatinine clearance (CLcr) between 30 to 60 mL/min were randomized to 75 mg, 150 mg, or placebo twice daily. Patients with creatinine clearance greater than 60 mL/min were randomized to 75 mg, 150 mg, 300 mg or placebo twice daily. In patients with creatinine clearance greater than 60 mL/min treatment with all doses of LYRICA statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Despite differences in dosing based on renal function, patients with creatinine clearance between 30 to 60 mL/min tolerated LYRICA less well than patients with creatinine clearance greater than 60 mL/min as evidenced by higher rates of discontinuation due to adverse reactions. For various degrees of improvement in pain from baseline to study endpoint, Figure 3 shows the fraction of patients achieving that degree of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study

The efficacy of LYRICA as adjunctive therapy in partial onset seizures was established in three 12-week, randomized, double-blind, placebo-controlled, multicenter studies in adult patients. Patients were enrolled who had partial onset seizures with or without secondary generalization and were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). Patients taking gabapentin were required to discontinue gabapentin treatment 1 week prior to entering baseline. During an 8-week baseline period, patients had to experience at least 6 partial onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 25 years in these 3 studies and the mean and median baseline seizure frequencies were 22.5 and 10 seizures per month, respectively. Approximately half of the patients were taking 2 concurrent AEDs at baseline. Among the LYRICA-treated patients, 80% completed the double-blind phase of the studies.

The efficacy of LYRICA for management of fibromyalgia was established in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and one six-month, randomized withdrawal study (F2). Studies F1 and F2 enrolled patients with a diagnosis of fibromyalgia using the American College of Rheumatology (ACR) criteria (history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). The studies showed a reduction in pain by visual analog scale. In addition, improvement was demonstrated based on a patient global assessment (PGIC), and on the Fibromyalgia Impact Questionnaire (FIQ).

Study F1: This 14-week study compared LYRICA total daily doses of 300 mg, 450 mg and 600 mg with placebo. Patients were enrolled with a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numeric pain rating scale and a score of greater than or equal to 40 mm on the 100 mm pain visual analog scale (VAS). The baseline mean pain score in this trial was 6.7. Responders to placebo in an initial one-week run-in phase were not randomized into subsequent phases of the study. A total of 64% of patients randomized to LYRICA completed the study. There was no evidence of a greater effect on pain scores of the 600 mg daily dose than the 450 mg daily dose, but there was evidence of dose-dependent adverse reactions [see Adverse Reactions (6.1)]. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study. The results are summarized in Figure 8 and Table 8.

For various degrees of improvement in pain from baseline to study endpoint, Figure 8 shows the fraction of patients achieving that degree of improvement. The figure is cumulative. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

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CARISOPRODOL 
carisoprodol   tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 49999-064 (0603-2582)
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CARISOPRODOL (CARISOPRODOL) CARISOPRODOL 350 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM  
HYPROMELLOSE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
Product Characteristics
Color white Score no score
Shape ROUND Size 12mm
Flavor Imprint Code 2410;V
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 49999-064-01 120 BOTTLE In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA040245 08/13/2010

Labeler - Lake Erie Medical DBA Quality Care Products LLC (831276758)
Establishment
Name Address ID/FEI Operations
Vintage Pharmaceuticals Huntsville 958430845 repack
Revised: 08/2010 Lake Erie Medical DBA Quality Care Products LLC