CARISOPRODOL AND ASPIRIN- carisoprodol and aspirin tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CARISOPRODOL (UNII: 21925K482H) (CARISOPRODOL - UNII:21925K482H), ASPIRIN (UNII: R16CO5Y76E) (ASPIRIN - UNII:R16CO5Y76E)
Available from:
Rising Pharmaceuticals, Inc.
INN (International Name):
CARISOPRODOL
Composition:
CARISOPRODOL 200 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Carisoprodol and Aspirin is indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. Carisoprodol and Aspirin 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 ). Carisoprodol and Aspirin is contraindicated in patients with a history of: - a serious GI complication (i.e., bleeding, perforations, obstruction) due to aspirin use - aspirin induced asthma (a symptom complex which occurs in patients who have asthma, rhinosinusitis, and nasal polyps who develop a severe, potentially fatal bronchospasm shortly after taking aspirin or other NSAIDs) - hypersensitivity reaction to carbamate such as meprobamate - acute intermittent prophyria The efficacy, safety, and pharmacokinetics of carisoprodol and Aspirin in pediatric patients less than 16 years
Product summary:
Carisoprodol and Aspirin Tablets, USP 200mg/325mg are red and white, round unscored convex, two layered tablets debossed on red layer with "CL" over "023" and plain on the white layer. The tablets are available in: Bottles of 100 NDC 64980-175-01. Bottles of 500 NDC 64980-175-05.
Authorization status:
Abbreviated New Drug Application
Authorization number:
64980-175-01, 64980-175-05

CARISOPRODOL AND ASPIRIN- carisoprodol and aspirin tablet

Rising Pharmaceuticals, Inc.

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CARISOPRODOL AND ASPIRIN

TABLETS, USP

200 mg/325 mg

CIV

Rx only

DESCRIPTION

Carisoprodol and Aspirin tablets, USP are a fixed-dose combination product containing the following

two products:

200 mg of carisoprodol, a centrally-acting muscle relaxant

325 mg of aspirin, an analgesic with antipyretic and anti-inflammatory properties

It is available as a two-layered, Red and White, round tablet for oral administration.

Carisoprodol: Chemically, carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3propanediol dicarbamate

and its molecular formula is C

H N O , with a molecular weight of 260.33. The structural formula

of carisoprodol is:

Aspirin: Chemically, aspirin (acetylsalicylic acid) is 2-(acetyloxy-, benzoic acid and its molecular

formula is C H O , with a molecular weight of 180.16. The structural formula of aspirin is:

Other ingredients in the Carisoprodol ·and Aspirin Tablets, drug product are Com starch, FD&C Red #

40 Aluminum Lake, Hydroxypropyl Cellulose, Lactose Anhydrous, Microcrystalline Cellulose,

Magnesium Stearate, Pregelatinized Starch, Sodium Starch Glycolate and Sodium Lauryl Sulfate.

CLINICAL PHARMACOLOGY

Mechanism of Action

Carisoprodol: 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.

Aspirin: The mechanism of action of aspirin in relieving pain is by inhibition of the body's production of

prostaglandins, which are thought to cause pain sensations by stimulating muscle contractions and

dilating blood vessels.

Pharmacodynamics

Carisoprodol: Carisoprodol is a centrally-acting muscle relaxant that does not directly relax tense

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 and Aspirin is unknown.

Aspirin: Aspirin is a non-narcotic analgesic with anti-inflammatory and anti-pyretic activity. Inhibition of

prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its

analgesic and antipyretic properties. In the CNS, aspirin works on the hypothalamus heat-regulating

center to reduce fever. Aspirin can cause serious gastrointestinal injury including bleeding, obstruction,

and perforations from ulcers possibly by inhibition of the production of prostaglandins, compromising

the defenses of the gastric mucosa and the activity of substances involved in tissue repair and ulcer

healing (see WARNINGS). Aspirin inhibits platelet aggregation by irreversibly inhibiting

prostaglandin cycle-oxygenase. This effect lasts for the life of the platelet and prevents the formation

of the platelet aggregating factor thromboxane A2.

Pharmacokinetics

Carisoprodol: The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a

study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg of

carisoprodol (see Table 1). 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 1: Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)

Carisoprodol

Meprobamate

Cmax (μg/mL)

1.8 ± 1.0

2.5 ± 0.5

(μg·hour/mL)

7.0 ± 5.0

46 ± 9.0

Tmax (hour)

1.7 ± 0.8

4.5 ± 1.9

(hour)

2.0 ± 0.5

9.6 ± 1.5

Absorption: Absolute bioavailability of carisoprodol has not been determined. After administration of a

single dose of 350 mg of carisoprodol, the mean time to peak plasma concentrations (Tmax) of

carisoprodol was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with 350 mg of

carisoprodol had no effect on the pharmacokinetics of carisoprodol.

Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme

CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with

Reduced CYP2C19 Activity below).

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination

half-life of approximately 2 hours after administration of a single dose of 350 mg of carisoprodol. The

half-life of meprobamate is approximately 10 hours after administration of a single dose of 350 mg of

carisoprodol.

Gender: Exposure of carisoprodol is higher in females than in male subjects (approximately 30 to 50%

on a weight adjusted basis). Overall exposure of meprobamate is comparable between female 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 a 4-fold increase in exposure to carisoprodol, and 50% reduced exposure to

meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in

Caucasians and African Americans is approximately 3 to 5% and in Asians is approximately 15 to 20%.

Aspirin:

Absorption: The rate of aspirin absorption from the gastrointestinal (GI) tract is dependent upon the

presence or absence of food, gastric pH (the presence or absence of GI antacids), and other

physiologic factors. Following absorption, aspirin is hydrolyzed to salicylic acid in the gut wall and

during first-pass metabolism with peak plasma levels of salicylic acid occurring within 1 to 2 hours of

dosing.

Distribution: Salicylic acid is widely distributed to all tissues and fluids in the body including the central

nervous system (CNS), breast milk, and fetal tissues. The highest concentrations are found in the plasma,

liver, kidneys, heart, and lungs. The protein binding of salicylate is concentration dependent, i.e.,

nonlinear. At plasma concentrations of salicylic acid < 100 μg/mL and > 400 μg/mL, approximately 90

and 76 percent of plasma salicylate is bound to albumin, respectively.

Metabolism: Aspirin, which has a half-life of about 15 minutes, is hydrolyzed in the plasma to salicylic

acid such that plasma levels of aspirin may not be detectable 1 to 2 hours after dosing. Salicylic acid,

which has a plasma half life of approximately 6 hours, is conjugated in the liver to form salicyluric

acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, gentisic acid, and gentisuric acid. At

higher serum concentrations of salicylic acid, the total clearance of salicylic acid decreases due to the

limited ability of the liver to form both salicyluric acid and phenolic glucuronide. Following toxic

doses of aspirin (e.g., > 10 grams), the plasma half-life of salicylic acid may be increased to over 20

hours.

Elimination: The elimination of salicylic acid is constant in relation to the plasma salicylic acid

concentration. Following therapeutic doses of aspirin, approximately 75, 10, 10, and 5 percent is found

excreted in the urine as salicyluric acid, salicylic acid, a phenolic glucuronide of salicylic acid, and an

acyl glucuronide of salicylic acid, respectively. As the urinary pH rises above 6.5, the renal clearance

of free salicylate increases from less than 5 percent to greater than 80 percent.

Alkalinization of the urine is a key concept in the management of salicylate overdose (see

OVERDOSAGE, Treatment of Overdosage). Clearance of salicylic acid is also reduced in patients

with renal impairment.

INDICATIONS AND USAGE

Carisoprodol and Aspirin is indicated for the relief of discomfort associated with acute, painful

musculoskeletal conditions in adults. Carisoprodol and Aspirin 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).

CONTRAINDICATIONS

Carisoprodol and Aspirin is contraindicated in patients with a history of:

a serious GI complication (i.e., bleeding, perforations, obstruction) due to aspirin use

aspirin induced asthma (a symptom complex which occurs in patients who have asthma,

rhinosinusitis, and nasal polyps who develop a severe, potentially fatal bronchospasm shortly after

taking aspirin or other NSAIDs)

hypersensitivity reaction to carbamate such as meprobamate

acute intermittent prophyria

WARNINGS

Carisoprodol:

Sedation

Carisoprodol has sedative properties 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, tricylic antidepressants) may be additive, appropriate caution should be exercised with patients

who take more than one of these CNS depressants simultaneously.

Drug Dependence, Withdrawal, and Abuse

In post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been

reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients

who have had a history of addiction or who used carisoprodol in combination with other drugs with

abuse potential. However, there have been post-marketing adverse event reports of carisoprodol-

associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been

reported following abrupt cessation after prolonged use. To reduce the chance of carisoprodol

dependence, withdrawal, or abuse, carisoprodol should be used with caution in addiction prone patients

and in patients taking other CNS depressants including alcohol, and carisoprodol should not be used

more than two to three weeks for the relief of acute musculoskeletal discomfort.

Carisoprodol, and one of its metabolites, meprobamate (a controlled substance), may cause dependence

(see CLINICAL PHARMACOLOGY).

Aspirin:

Serious Gastrointestinal Adverse Reactions

Aspirin can cause serious gastrointestinal (GI) adverse reactions including bleeding, perforation, and

obstruction of the stomach, small intestine, or large intestine, which can be fatal. Aspirinassociated

serious Gl adverse reactions can occur anywhere along the Gl tract, at any time, with or without

warning symptoms. Patients at higher risk of aspirin-associated serious upper Gl adverse reactions

include patients with a history of aspirin-associated Gl bleeding from ulcers (complicated ulcers), a

history of aspirin-associated ulcers (uncomplicated ulcers), geriatric patients, patients with poor

baseline health status, patients taking higher doses of aspirin, and patients taking concomitant

anticoagulants, NSAIDs, and/or large amounts of alcohol. To minimize the risk for aspirin-associated

Gl serious adverse reaction, the lowest effective aspirin dose should be used for the shortest possible

duration.

Anaphylaxis and Anaphylactoid Reactions

Aspirin may cause an increased risk of serious anaphylaxis and anaphylactoid reactions, which can

occur in patients without known prior exposure to aspirin (see CONTRAINDICATIONS). Patients

with a serious anaphylaxis or anaphylactoid reaction should receive emergency care.

PRECAUTIONS

Patients with impaired renal or hepatic function

The safety and pharmacokinetics of Carisoprodol and Aspirin in patients with renal or hepatic

impairment have not been evaluated.

Carisoprodol:

Since carisoprodol is excreted by the kidney and is metabolized in the liver, caution should be

exercised if carisoprodol is administered to patients with impaired renal or hepatic function.

Carisoprodol is dialyzable by hemodialysis and peritoneal dialysis.

Seizures

There have been postmarketing 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).

Aspirin:

Gastrointestinal Adverse Reactions

In addition to serious gastrointestinal adverse reactions, the use of aspirin is also associated with

gastritis, gastrointestinal erosions, abdominal pain, heartburn, vomiting, and nausea (see WARNINGS,

Serious Gastrointestinal Adverse Reactions).

Information for Patients:

Patients should be advised to contact their health care provider if they experience any adverse reactions

to Carisoprodol and Aspirin Tablets.

Carisoprodol:

1. Patients should be advised 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, Sedation).

2. Patients should be advised 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, Sedation).

3. Patients should be advised 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 postmarketing 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.

Aspirin:

1. Patients should be warned that aspirin can cause epigastric discomfort, gastric and duodenal ulcers,

and serious GI adverse reactions, such as bleeding, perforation, and/or obstruction of the stomach

or intestines, which may result in hospitalization and death. Although serious GI bleeding can occur

without warning symptoms (e.g., hematemesis, melena, hematochezia), patients should be alert for

these symptoms and should seek urgent medical care if any of these indicative symptoms occur (see

WARNINGS, Serious Gastrointestinal Adverse Reactions). In addition, patients should be alert

for symptoms of ulcers (e.g., night time epigastric discomfort, vomiting, weight loss) and should

seek medical attention if these symptoms occur. Patients who consume three or more alcoholic

drinks every day should be counseled about the GI bleeding risks involved with the use of aspirin

with alcohol.

2. Patients should be informed of the symptoms of an anaphylactoid reaction or anaphylaxis (e.g.,

hives, difficulty breathing, swelling of face or throat). If these symptoms occur, patients should be

instructed to seek immediate emergency help.

Drug Interactions

Carisoprodol:

The sedative effect 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,

Sedation).

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate (see CLINICAL

PHARMACOLOGY). Co-administration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine,

with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of

meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John’s Wort, with

carisoprodol could result in decreased exposure of carisoprodol and increased exposure of

meprobamate. Low dose aspirin also showed an induction effect of CYP2C19. The full

pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety

of carisoprodol is unknown.

Aspirin: Clinically important interactions may occur when certain drugs or alcohol are administered

concomitantly with aspirin.

Alcohol: Concomitant use of aspirin with ≥ 3 alcoholic drinks may increase the risk of GI bleeding (see

WARNINGS, Serious Gastrointestinal Adverse Reactions).

Anticoagulants: Concomitant use of aspirin and anticoagulants (e.g., heparin, warfarin, clopidogrel)

increase the risk of GI bleeding (see WARNINGS, Serious Gastrointestinal Adverse Reactions).

Additionally, aspirin can displace warfarin from protein binding sites, leading to prolongation of the

international normalized ratio (INR).

Antihypertensives: The concomitant administration of aspirin with angiotensin converting enzyme (ACE)

inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and diuretics may diminish the

hypotensive effects of these anti-hypertensive products due to aspirin’s inhibition of renal

prostaglandins, which may lead to decreased renal blood flow and increased sodium and fluid retention.

Concomitant use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide

due to competition at the renal tubule for secretion.

Corticosteroids: Concomitant administration of aspirin and corticosteroids may decrease salicylate

plasma levels.

Methotrexate: Aspirin may enhance the toxicity of methotrexate due to displacement of methotrexate

from its plasma protein binding sites and/or reduction of the renal clearance of methotrexate.

Nonsteroidal anti-inflammatory drugs (NSAIDs): The concurrent use of aspirin with selective and

nonselective NSAIDs increases the risk of serious GI adverse reactions (see WARNINGS, Serious

Gastrointestinal Adverse Reactions).

Oral Hypoglycemics Agents: Aspirin may increase the serum glucose lowering action of insulin and

sulfonylureas leading to hypoglycemia.

Products that effect urinary pH: Ammonium chloride and other drugs that acidify the urine can elevate

plasma salicylate concentrations. In contrast, antacids, by alkalinizing the urine, may decrease plasma

salicylate concentrations.

Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid and sulfinpyrazone.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No long-term studies of carcinogens have been done with carisoprodol and Aspirin.

Carisoprodol: Long term studies in animals have not been performed to evaluate the carcinogenic

potential of carisoprodol.

Carisoprodol was 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.

Aspirin: Administration of aspirin for 68 weeks in the feed of rats was not carcinogenic. In the Ames

Salmonella assay, aspirin was not mutagenic; however, aspirin did induce chromosome aberrations in

cultured human fibroblasts. Aspirin has been shown to inhibit ovulation in rats (see Pregnancy).

Pregnancy:

Pregnancy Category D.

It is not known whether Carisoprodol and Aspirin can cause fetal harm when administered to a pregnant

woman or can affect reproduction capacity. Adequate animal reproduction studies have not been

conducted with Carisoprodol and Aspirin. Carisoprodol and Aspirin should be given to a pregnant

woman only if clearly needed.

Carisoprodol: There are no data on the use of carisoprodol during human pregnancy. Animal studies

indicate that carisoprodol crosses the placenta and results in adverse effects on fetal growth and

postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an approved anxiolyic.

Retrospective, postmarketing studies do not show a consistent association between maternal use of

meprobamate and an increased risk for particular congenital malformations.

Teratogenic effects: Animal studies have not adequately evaluated the teratogenic effects of

carisoprodol. There was no increase in the incidence of congenital malformations noted in the

reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective, postmarketing

studies of meprobamate during human pregnancy were equivocal for demonstrating an increased risk of

congenital malformations following the first trimester exposure. Across studies that indicated an

increased risk, the types of malformations were inconsistent.

Nonteratogenic effects: In animal studies, carisoprodol reduced fetal weights, postnatal weight gain, and

postnatal survival at maternal doses equivalent to 1 to 1.5 times the human dose (based on a body surface

area comparison). Rats exposed to meprobamate in-utero showed behavioral alterations that persisted

into adulthood. For children exposed to meprobamate in-utero, one study found no adverse effects on

mental or motor development or IQ scores. Carisoprodol should be used during pregnancy only if the

potential benefit justifies the risk to the fetus.

Aspirin:

Teratogenic effects: Prior to 30 weeks gestation, aspirin should be used during pregnancy only if the

potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, aspirin should be

avoided by pregnant women as premature closure of the fetal ductus arteriosus which may result in fetal

pulmonary hypertension and fetal death. Salicylate products have also been associated with alterations in

maternal and neonatal hemostasis mechanisms, decreased birth weight, increased incidence of

intracranial hemorrhage in premature infants, stillbirths, and neonatal death. Studies in rodents have show

salicylates to be teratogenic when given in early gestation, and embryocidal when given in later

gestation in doses considerably greater than usual therapeutic doses in humans.

Labor and Delivery

Carisoprodol: There is no information about the effects of carisoprodol on the mother and the fetus

during labor and delivery.

Aspirin: Ingestion of aspirin within one week of delivery or during labor may prolong delivery or lead

to excessive blood loss in the mother, fetus, or neonate. Prolonged labor due to prostaglandin inhibition

has been reported with aspirin use.

Nursing Mothers

Carisoprodol: Very limited data in humans show that carisoprodol is present in breast milk and may reach

concentrations two to four times the maternal plasma concentrations. In one case report, a breast-fed

infant received about 4 to 6% of the maternal daily dose though breast milk and experienced no adverse

effects. However, milk production was inadequate and the baby was supplemented with formula. In

lactation studies in mice, female pup survival and pup weight at weaning was decreased. This

information suggests that maternal use of carisoprodol may lead to reduced or less effective infant

feeding (due to sedation) and/or decreased milk production. Caution should be exercised when

carisoprodol is administered to a nursing woman.

Aspirin: Nursing mothers should avoid the use of aspirin because salicylate is excreted in breast milk

which may lead to bleeding in the infant.

Pediatric Use:

The efficacy, safety, and pharmacokinetics of carisoprodol and Aspirin in pediatric patients less than 16

years of age have not been established.

Geriatric Use:

The efficacy, safety, and pharmacokinetics of Carisoprodol and Aspirin in patients over 65 years of age

have not been established.

ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals at 1-201-961-

9000 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch.

The following adverse reactions which have occurred with the administration of the individual

products alone may also occur with the use of carisoprodol and Aspirin tablets. The following events

have been reported during post-approval individual use of carisoprodol and aspirin. 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.

Carisoprodol: The following events have been reported during post-approval 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).

Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache,

depressive reactions, syncope, insomnia, and seizures (see OVERDOSAGE).

Gastrointestinal: Nausea, vomiting, and epigastric discomfort.

Hematologic: Leukopenia, pancytopenia.

Aspirin: The most common adverse reactions associated with the use of aspirin have been

gastrointestinal, including abdominal pain, anorexia, nausea, vomiting, gastritis, and occult bleeding (see

WARNINGS, Serious Gastrointestinal Adverse Reactions and PRECAUTIONS, Gastrointestinal

Adverse Reactions). Other adverse reactions associated with the use of aspirin include elevated liver

enzymes, rash, pruritus, purpura, intracranial hemorrhage, interstitial nephritis, acute renal failure, and

tinnitus. Tinnitus may be a symptom of high serum salicylate levels (see OVERDOSAGE).

DRUG ABUSE AND DEPENDENCE

Carisoprodol is not a Controlled Substance (see WARNINGS).

Discontinuation of carisoprodol in animals or in humans after chronic administration can produce

withdrawal signs, and there are published case reports of human carisoprodol dependence.

In vitro studies demonstrate that Carisoprodol elicits barbiturate-like effects. Animal behavioral studies

indicate that carisoprodol produces rewarding effects. Monkeys self administer carisoprodol. Drug

discrimination studies using rats indicate that carisoprodol has positive reinforcing and discriminating

effects similar to barbital, meprobamate, and chlordiazepoxide.

OVERDOSAGE

Signs and Symptoms: Any of the following signs and symptoms which have been reported with

overdose of the individual products may occur with overdose of carisoprodol and Aspirin and may be

modified to a varying degree by the effects of the other products present in carisoprodol and Aspirin.

Carisoprodol: 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. 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 nonaccidental overdoses of Carisoprodol have been reported alone or in

combination with CNS depressants.

Aspirin: Salicylate toxicity may result from an overdose of an acute ingestion or chronic intoxication.

Mild to moderate salicylate poisoning is usually associated with plasma salicylic concentrations about

200 μg/mL and is characterized by tinnitus, hearing difficulty, headache, dim vision, dizziness,

tachypnea, increased thirst, nausea, vomiting, sweating, and diarrhea. In the early stages of overdose,

CNS stimulation and respiratory alkalosis can occur; however, in the later stages CNS depression and

metabolic acidosis can occur.

Symptoms and signs of severe salicylate poisoning, associated with plasma salicylic concentrations

greater that 400 μg/mL, include hyperthermia, dehydration, delirium, GI hemorrhage, pulmonary edema,

and CNS depression (e.g., coma). Death is usually due to respiratory failure or cardiovascular collapse.

Overdose of aspirin in pediatric patients: Salicylate poisoning should be considered in pediatric patients

with symptoms of vomiting, hyperpnea, and hyperthermia. Salicylate poisoning should be considered in

infants with metabolic acidosis and all pediatric patients with severe salicylate poisoning.

Treatment of Overdosage: Provide symptomatic and supportive treatment, as indicated. For more

information on the management of an overdose of Carisoprodol and Aspirin tablets, USP contact a

Poison Control Center.

Carisoprodol: Basic life support measures should be instituted as dictated by the clinical presentation of

the carisoprodol overdose. Induced emesis is not recommended due to the risk of CNS and respiratory

depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered

soon after ingestion (within one hour). 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. The following types of treatment have been used successfully with

an overdose of meprobamate, a metabolite of carisoprodol: activated charcoal (oral or via nasogastric

tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful

monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible

relapse due to incomplete gastric emptying and delayed absorption

Aspirin: Since there are no specific antidotes for salicylate poisoning, the aim of the treatment is to

enhance elimination of salicylate; reduce further salicylate absorption; correct fluid, electrolyte, or

acid/ibase imbalances; and provide cardio-respiratory support. The acidbase status should be followed

closely with serial serum pH determinations (using arterial blood gas). If acidosis is present,

intravenous sodium bicarbonate should be given, along with adequate hydration, until salicylate levels

decrease to within the therapeutic range. To enhance elimination, forced diuresis and alkalinization of

the urine may be beneficial. Gastric emptying and/or lavage are recommended as soon as possible after

ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of

activated charcoal is beneficial, if less than 3 hours have passed since ingestion. Charcoal absorption

should not be employed prior to emesis and lavage. In patients with renal insufficiency or in cases of

life-threatening aspirin intoxication, hemodialysis or peritoneal dialysis is usually required.

Additional treatment of aspirin overdose in pediatric patients: Pediatric patients should be sponged with

tepid water. Infusion of glucose may be required to control hypoglycemia. Exchange transfusion may be

indicated in infants and young children.

DOSAGE AND ADMINISTRATION

The recommended dose of Carisoprodol and Aspirin tablets, is 1 or 2 tablets, four times daily in adults .

One Carisoprodol and Aspirin tablet contains 200 mg of Carisoprodol and 325 mg of Aspirin. The

maximum daily dose (i.e., two tablets taken four times daily) will provide 1600 mg of carisoprodol and

2600 mg of aspirin per day. The recommended maximum duration of Carisoprodol and Aspirin tablets

use is up to two or three weeks.

HOW SUPPLIED

Carisoprodol and Aspirin Tablets, USP 200mg/325mg are red and white, round unscored convex, two

layered tablets debossed on red layer with "CL" over "023" and plain on the white layer. The tablets are

available in:

Bottles of 100 NDC 64980-175-01.

Bottles of 500 NDC 64980-175-05.

Storage: Store at controlled room temperature 20° - 25°C (68° - 77°F). Protect from moisture.

Dispense in a tight container.

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals at 1-201-961-

9000 or FDA at 1-800-FDA-1 088 orwww.fda.gov/medwatch.

Manufactured for:

Rising Pharmaceuticals, Inc.

Allendale, NJ 07401

Manufactured by:

Mirror Pharmaceuticals, LLC

Fairfield, NJ 07004 USA

5507

Rev 02/12

PRINCIPAL DISPLAY PANEL - Principal Display Panel – 100-count Bottle

Rising® NDC 64980-175-01 CIV

Carisoprodol and

Aspirin Tablets, USP

200 mg/325 mg

100 Tablets

Rx Only

CARISOPRODOL AND ASPIRIN

carisoprodol and aspirin tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 49 8 0 -175

Route of Administration

ORAL

Rising Pharmaceuticals, Inc.

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CARISO PRO DO L (UNII: 219 25K48 2H) (CARISOPRODOL - UNII:219 25K48 2H)

CARISOPRODOL

20 0 mg

ASPIRIN (UNII: R16 CO5Y76 E) (ASPIRIN - UNII:R16 CO5Y76 E)

ASPIRIN

325 mg

Inactive Ingredients

Ingredient Name

Stre ng th

STARCH, CO RN (UNII: O8 232NY3SJ)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

HYDRO XYPRO PYL CELLULO SE (UNII: RFW2ET6 71P)

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

STARCH, CO RN (UNII: O8 232NY3SJ)

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

Product Characteristics

Color

RED, WHITE

S core

no sco re

S hap e

ROUND

S iz e

12mm

Flavor

Imprint Code

CL;0 23

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 49 8 0 -175-0 1

10 0 in 1 BOTTLE

2

NDC:6 49 8 0 -175-0 5

50 0 in 1 BOTTLE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 8 32

0 1/0 7/20 10

Labeler -

Rising Pharmaceuticals, Inc. (041241766)

Registrant -

Mirror Pharmaceuticals, LLC (964680206)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Mirro r Pharmaceuticals, LLC

9 6 46 8 0 20 6

MANUFACTURE

Revised: 6/2012

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