Patients with impaired renal or hepatic function
The safety and pharmacokinetics of Soma Compound with
Codeine in patients with renal or hepatic impairment have not been evaluated.
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.
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).
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).
Obscuring Medical Conditions
Opioids, including codeine phosphate, may obscure the
clinical course of patients with head injuries because of the CNS depressive
effects of opioids. In addition, opioids, including codeine phosphate, may
obscure the symptoms and/or signs that are used for the diagnosis or for the
monitoring of patients with acute abdominal conditions.
Ultra-rapid Metabolizers of Codeine
Some patients may be ultra-rapid metabolizers of codeine
phosphate due to a specific CYP2D6*2x2 genotype. These patients convert codeine
into its active metabolite, morphine, more rapidly and completely than patients
who are normal metabolizers of codeine, resulting in higher than expected serum
morphine levels. Even at labeled dosage regimens of codeine phosphate, patients
who are ultra-rapid metabolizers may experience overdose symptoms such as
respiratory depression, extreme sleepiness, or delirium. Toxic serum levels of
morphine have been reported in infants of nursing mothers who may be
ultra-rapid metabolizers (see PRECAUTIONS, Nursing Mothers). The prevalence
of this CYP2D6 phenotype has been estimated at 16 to 28% in North Africans,
Ethiopians, and Arabs; 1 to 10% in Caucasians; 3% in African Americans; and 0.5
to 1% in Chinese, Japanese, and Hispanics. Data is not available for other
ethnic groups. When healthcare providers prescribe codeine-containing products,
they should choose the lowest effective dose for the shortest period of time.
Use in Patients with Pancreatic or Biliary Duct Disease
Opioids, including codeine phosphate, should be used with caution
in patients with pancreatic or biliary duct disease because opioids may cause
spasm of the sphincter of Oddi and diminish pancreatic and/or biliary
Carcinogens, Mutagenesis, Impairments of Fertility:
No long-term studies of carcinogens have been done with Soma
Compound with Codeine.
Long tern 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 vitro 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 spend 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
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 Category D
It is not known whether Soma Compound with Codeine (carisoprodol, aspirin, and codeine phosphate tablets) can cause
fetal harm when administered to a pregnant woman or can affect reproduction
capacity. Adequate animal reproduction studies have not been conducted with
Soma Compound with Codeine (carisoprodol, aspirin, and codeine phosphate tablets) . Soma Compound with Codeine (carisoprodol, aspirin, and codeine phosphate tablets) should be given to a
pregnant woman only if clearly needed.
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,
post-marketing studies do not show a consistent association between maternal
use of meprobamate and an increased risk for particular congenital
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,
post-marketing 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.
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
There is no information about the effects of carisoprodol on
the mother and the fetus during labor and delivery.
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.
The use of codeine phosphate during labor may lead to
respiratory depression in the neonate.
Very limited data in humans show that carisoprodol is
present in break 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.
Nursing mothers should avoid the use of aspirin because
salicylate is excreted in breast milk which may lead to bleeding in the infant.
Codeine is secreted into human milk. In women with normal
codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted
into human milk is low. Despite the common use of codeine products to manage
postpartum pain, reports of codeine-associated adverse reactions in nursing
infants are rare. Nursing mothers who are ultra-rapid metabolizers of codeine
have higher-than-expected levels of morphine (the active metabolite of codeine)
in their blood, leading to higher levels of morphine in their breast milk and
potentially dangerously high serum morphine levels in their breastfed infants.
Therefore, in nursing mothers who are ultra-rapid metabolizers of codeine, the
maternal use of codeine can lead to serious adverse reactions, including death;
in their nursing infants and in the nursing mothers (see PRECAUTIONS, Ultra-rapid
Metabolizers of Codeine).
Prior to prescribing nursing mothers codeine phosphate, the
risk of infant exposure to codeine and morphine through breast milk should be
weighed against the benefits of breastfeeding for both the mother and the
infant. If a codeine containing product is selected, the lowest dose should be
prescribed for the shortest period of time to achieve the desired clinical
effect. Prescribers should closely monitor mother-infant pairs and notify
treating pediatricians about the use of codeine during breastfeeding.
The efficacy, safety, and pharmacokinetics of Soma Compound
with Codeine in pediatric patients less than 16 years of age have not been
The efficacy, safety, and pharmacokinetics of Soma Compound
with Codeine in pediatric patients over 65 years of age have not been