Usual Adult Dose for Allergic Rhinitis

Immediate-release (suspension, liquid, tablets):
1 dose orally every 4 to 6 hours as needed

• Chlorpheniramine: Single dose: up to 4 mg; Maximum dose: 24 mg/24 hours
• Codeine: Single dose: up to 20 mg; Maximum dose: 120 mg/24 hours

Maximum doses should not exceed maximum dose of either of the single ingredient doses

Extended-release suspension: chlorpheniramine polistirex 2.8 mg/codeine polistirex 14.7 mg per 5 mL (equivalent to chlorpheniramine maleate 4 mg/codeine phosphate 20 mg per 5 mL)
10 mL orally every 12 hours
Maximum dose: 20 mL/24 hours

Comments:

• Liquid preparations should be measured with an accurate milliliter measuring device.
• Shake oral suspensions well before measuring dose.

Uses: For the temporary relief of cough due to minor throat and bronchial irritations as may occur with the common cold or inhaled irritants; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies.

Usual Adult Dose for Cough and Nasal Congestion

Immediate-release (suspension, liquid, tablets):
1 dose orally every 4 to 6 hours as needed

• Chlorpheniramine: Single dose: up to 4 mg; Maximum dose: 24 mg/24 hours
• Codeine: Single dose: up to 20 mg; Maximum dose: 120 mg/24 hours

Maximum doses should not exceed maximum dose of either of the single ingredient doses

Extended-release suspension: chlorpheniramine polistirex 2.8 mg/codeine polistirex 14.7 mg per 5 mL (equivalent to chlorpheniramine maleate 4 mg/codeine phosphate 20 mg per 5 mL)
10 mL orally every 12 hours
Maximum dose: 20 mL/24 hours

Comments:

• Liquid preparations should be measured with an accurate milliliter measuring device.
• Shake oral suspensions well before measuring dose.

Uses: For the temporary relief of cough due to minor throat and bronchial irritations as may occur with the common cold or inhaled irritants; temporarily decreases runny nose and reduces sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies.

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: 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; MEDICATION ERRORS; CYTOCHROME CYP450 (CYP450) 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME:

• Use of this product may lead to opioid addiction, abuse, and misuse, which can lead to overdose and death.
• Reserve use of this drug for adults for whom cough suppression benefits outweigh risks, and who have had adequate assessment of the cough aetiology.
• Assess each patients risks prior to prescribing; prescribe for the shortest duration consistent with individual treatment goals, and monitor all patients regularly for development of addiction or abuse; refill only after evaluating the need for continued treatment.
• 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.
• Serious, life-threatening, or fatal respiratory depression may occur with use.
• Monitor for respiratory depression, especially at the beginning of therapy or in high risk patients.
• Accidental ingestion of even one dose of this drug, especially by children, can cause a fatal overdose of codeine.
• Life-threatening respiratory depression and death have occurred in children who received codeine; most of the 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.
• Ensure accuracy when prescribing, dispensing, and administering this drug.
• Dosing errors can cause accidental overdose and death.
• Always use an accurate milliliter measuring device when measuring and administering liquid medications.
• The effects of concomitant use or discontinuation of CYP450 3A4 inhibitors or inhibitors, or 2D6 inhibitors with codeine are complex and require careful consideration of the effects on the parent drug, codeine, and the active metabolite morphine.
• Avoid use in patients taking CYP450 3A4 inhibitors or inducers, or CYP450 2D6 inhibitors.
• Concomitant use of opioids with benzodiazepines or other central nervous system (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.
• Use is not recommended in pregnant women.
• Prolonged use during pregnancy may cause neonatal opioid withdrawal syndrome, which can be life-threatening if not recognized and treated, and requires management according to neonatology expert protocols.
• If used for a prolonged period during pregnancy, advise the patient of the neonatal opioid withdrawal syndrome risk and ensure appropriate treatment will be available.

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.

Safety and efficacy of extended-release oral suspension have not been established in patients younger than 18 years.
Safety and efficacy of immediate-release oral suspension have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III (extended-release); Schedule V (immediate-release)

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
• Shake suspension well prior to measuring dose

Storage requirements:

• Protect from moisture and light

General:

• 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.
• Codeine use is contraindicated in the postoperative period in children who have undergone tonsillectomy and/or adenoidectomy.
• 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.

Monitoring:

• 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.

Patient advice:

• Advise patients to always use an accurate milliliter measuring device when measuring and giving liquid medications.
• Inform patients that a household teaspoon is not an accurate measuring device and could lead to overdosage and serious adverse effects.
• If a measuring device is not provided, a pharmacist can provide an appropriate measuring device and instructions for measuring the correct dose.
• 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 until adverse effects are determined.
• 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.