Usual Adult Dose for Cough

Promethazine 6.25 mg/ Codeine 10 mg per 5 mL:
Average effective dose: 5 mL orally every 4 to 6 hours as needed
Maximum dose: 30 mL (promethazine 37.5 mg; codeine: 60 mg) in 24 hours

Comments:

• Liquid preparations should be measured with an accurate milliliter measuring device.

Renal Dose Adjustments

Use with caution, especially in patients with severe renal impairment

Liver Dose Adjustments

Use with caution, especially in patients with severe hepatic impairment

Dose Adjustments

Elderly: Use with caution generally starting at the lower end of the dosing range.

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: ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; RISK EVALUATION AND MITIGATION STRATEGY (REMS)

• 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. Codeine is contraindicated in children younger than 12 years of age and in children of any age who are undergoing tonsillectomy and/or adenoidectomy. Avoid use in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effect of codeine.
• Promethazine and Respiratory Depression in Children: Postmarketing cases of respiratory depression, including fatalities, have been reported with use of promethazine in pediatric patients. Children may be particularly sensitive to the additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine.
• Risks from Concomitant Use with Benzodiazepine or Other CNS Depressants: Concomitant use of opioids with other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.
• 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 consider other tools to improve patient, household, and community safety.

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally with or without food
• Oral measuring devices should be used to ensure accuracy in dosing; a household teaspoon should not be considered an accurate measuring device
• Syrup contains 7% alcohol

• Protect from moisture and light

• Patients who are ultra-rapid metabolizers of codeine due to a CYP450 2D6 polymorphism, will convert codeine more rapidly and completely to morphine resulting in unexpectedly high morphine levels, which may be life-threatening.
• The US FDA recommends against use of codeine-containing cough and cold medications in patients less than 18 years because it has been determined that the risks outweigh benefits.

• Cardiovascular: Monitor for signs of hypotension, especially in those whose blood pressure is compromised
• Respiratory: Monitor for respiratory depression
• Gastrointestinal: Monitor for constipation and decreased bowel motility in post-operative patients.
• Patients should be monitored for the development of addiction, abuse, or misuse.

• Patients should understand that codeine use can result in addiction, abuse, and misuse.
• Patients should understand risks of life-threatening respiratory depression and when this risk is greatest; patients should be aware that a genetic mutation may result in greater codeine toxicity in some patients; breastfed infants of women who have this genetic mutation are also at risk.
• Women who are breastfeeding, pregnant, or planning to become pregnant should speak to their healthcare provider before using this product.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery while taking this drug.
• Concomitant use of alcohol, sedatives, and tranquilizers may increase drowsiness; patients should avoid alcohol and consult with their healthcare provider regarding concomitant use of other CNS depressants.
• Patients should be cautioned to avoid prolonged sun exposure and report any involuntary muscle movement.
• 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.