Drug Class: Skeletal muscle relaxant combinations
Usual Adult Dose for Muscle Spasm
1 to 2 tablets 4 times a day
Maximum daily dose: 8 tablets/day (carisoprodol: 1600 mg; aspirin: 2600 mg; codeine: 128 mg)
Duration of therapy: Up to 2 or 3 weeks
Comments:
- Initiate therapy, taking into account severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
- Use should be limited to short periods (up to 3 weeks) since acute, painful musculoskeletal conditions are generally of short duration and evidence of effectiveness beyond this time period has not been established.
Use: For the relief of discomfort associated with acute, painful musculoskeletal conditions.
Usual Adult Dose for Pain
1 to 2 tablets 4 times a day
Maximum daily dose: 8 tablets/day (carisoprodol: 1600 mg; aspirin: 2600 mg; codeine: 128 mg)
Duration of therapy: Up to 2 or 3 weeks
Comments:
- Initiate therapy, taking into account severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
- Use should be limited to short periods (up to 3 weeks) since acute, painful musculoskeletal conditions are generally of short duration and evidence of effectiveness beyond this time period has not been established.
Use: For the relief of discomfort associated with acute, painful musculoskeletal conditions.
Renal Dose Adjustments
Use with caution
Liver Dose Adjustments
Use with caution
Dose Adjustments
Elderly: Dose selection should be cautious, generally starting at the low end of the dosing range.
Interactions with Drugs Affecting CYP450 Isoenzymes: The effects of concomitant use or discontinuation of CYP450 3A4 inducers/inhibitors or CYP450 2D6 inhibitors are complex; concomitant use requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.
Discontinuation:
- Do not discontinue abruptly in the drug-dependent patient; use a gradual downward titration to prevent signs/symptoms of withdrawal.
Precautions
The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm
US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:
- Addiction, Abuse, and Misuse: This drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
- Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
- Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur; monitor for respiratory depression, especially during initiation and following dose increases.
- Accidental Ingestion: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose of codeine.
- Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP450 2D6 polymorphism. This drug is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of this drug in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.
- Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If prolonged opioid use is required in a pregnant woman, the patient should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
- Interactions with Drugs Affecting CYP450 Isoenzymes: The effects of concomitant use or discontinuation of CYP450 3A4 inducers/inhibitors or CYP450 2D6 inhibitors are complex; concomitant use requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.
- Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Concomitant use should be reserved for use in patients for whom alternative treatment options are inadequate. If needed, limit dose and duration to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.
CONTRAINDICATIONS:
- Children younger than 12 years
- Post-operative management of pain in children younger than 18 years following tonsillectomy and/or adenoidectomy
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
- Concurrent use or within 14 days of MAOIs
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to codeine, aspirin, or a carbamate such as meprobamate (e.g. anaphylaxis)
- Hemophilia
- Reye's Syndrome
- Known allergy to NSAIDs
- Syndrome of asthma, rhinitis, and nasal polyps
- Acute intermittent porphyria
Safety and efficacy have not been established in patients younger than 18 years.
Consult WARNINGS section for additional precautions.
US Controlled Substance: Schedule: III
Dialysis
Data not available
Other Comments
Administration advice:
- Duration of therapy should be limited to short-term treatment
General:
- Dependence, withdrawal, and abuse have been reported; the risk of abuse should be assessed prior to prescribing.
- Treatment duration should not exceed up to 2 to 3 weeks; if musculoskeletal symptoms persist, patients should be re-evaluated.
Monitoring:
- Monitor for sedation
- Monitor for signs of abuse and overdose
Patient advice:
- Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
- Patients should understand that this product contains aspirin and that aspirin may cause a wide range of gastrointestinal adverse reactions including potentially fatal events; patients should be informed of signs or symptoms to watch for and which require prompt medical attention.
- Patients should be advised that this drug may cause drowsiness and dizziness and that there have been reports of motor vehicle accidents following use; patients should be advised to avoid hazardous activities such as driving while taking this drug.
- Patients should be advised to avoid concomitant use with alcohol and to check with their health care professional before taking other CNS depressants.
- Patients should understand that this drug has been associated with cases of dependence, withdrawal, and abuse; use should be limited to less than 3 weeks duration.
- Patients should understand the risks of life-threatening respiratory depression and when this risk is greatest; patients should be aware that a genetic mutation may result in greater toxicity in some patients.
- For women who are breastfeeding and have this genetic mutation, their infant will be at risk for morphine toxicity; nursing mothers should be instructed to seek immediate medical attention for infants experiencing increased sleepiness, difficulty breastfeeding, breathing difficulties, or limpness.
- Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.
