Dosing and uses of Codeine
Adult dosage forms and strengths
tablet: Schedule II
- 15mg
- 30mg
- 60mg
injection solution
- 15mg/mL
- 30mg/mL
Pain
15-60 mg PO/SC/IM q4-6hr PRN; not to exceed 360 mg/day in naive patients
Dosing considerations
- Patients with prior opioid exposure may require higher initial doses
Cough
7.5-20 mg PO q4-6hr PRN; not to exceed 120 mg/24 hours
Pediatric dosage forms and strengths
tablet: Schedule II
- 15mg
- 30mg
- 60mg
oral solution: Schedule II
- 30mg/mL
injection solution
- 15 mg/mL
- 30 mg/mL
Pain
0.5-1 mg/kg IM/PO/SC q4-6hr PRN; not to exceed 60 mg/dose
Dosing considerations
- See Black box warnings and Contraindications sections for warning regarding postoperative use following tonsillectomy and/or adenoidectomy
- Potential toxic dose <6 years: 2 mg/kg
Cough
Infants: Safety and efficacy not established
2-6 years: 1-1.5 mg/kg/day divided q4-6hr PO/IM/SC; not to exceed 30 mg/day
6-12 years: 1-1.5 mg/kg/day divided q4-6hr PO/IM/SC; not to exceed 60 mg/day
>12 years: As in adults
Dosing considerations
- Potential toxic dose <6 years: 2 mg/kg
Codeine adverse (side) effects
>10%
Constipation
Drowsiness
1-10%
Hypotension
Tachycardia or bradycardia
Confusion
Dizziness
False feeling of well-being
Headache
Lightheadedness
Malaise
Paradoxical CNS stimulation
Restlessness
Rash, urticaria
Anorexia
Nausea, vomiting
Xerostomia
Ureteral spasm, urination decreased
LFTs increased
Burning at injection site
Weakness
Blurred vision
Dyspnea
Histamine release
<1%
Hypotension, with IV use
Anaphylactoid reaction (rare)
Seizure, with excessive doses
Respiratory depression
Warnings
Black Box Warning
Respiratory depression and death reported in children who received codeine following tonsillectomy and/or adenoidectomy that were also ultra-rapid metabolizers of codeine due to CYP2D6 polymorphism
Contraindications
Absolute: Acute abdominal condition, diarrhea associated w/ toxins, pseudomembranous colitis, respiratory depression, postoperative use in children following tonsillectomy and/or adenoidectomy (see Black box warnings)
Relative: Asthma (acute), inflammatory bowel disease, respiratory impairment
Cautions
Cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder disease, head injury, hepatic impairment, hypothyroidism, increased ICP, prostatic hypertrophy, renal impairment, seizures with epilepsy, urethral stricture, urinary tract surgery
Do NOT give IV, because of severe adverse reactions
Risk of life-threatening side effects in nursing infants, especially if mother is an ultra-rapid metabolizer of codeine
Prescribe an alternate analgesic for postoperative pain control in children undergoing tonsillectomy and/or adenoidectomy
Postoperative pain in children
- Deaths have occurred in children with obstructive sleep apnea who received codeine for postoperative pain following tonsillectomy and/or adenoidectomy
- Codeine is converted to morphine by the liver; these children had evidence of being ultra-rapid metabolizers (via CYP2D6) of codeine, which is an inherited (genetic) ability that causes codeine to be converted rapidly into life-threatening or fatal amounts of morphine
Pregnancy and lactation
Pregnancy category: C; D if used for prolonged periods or near term
Lactation: Excreted in breast milk; use with caution (AAP Committee states "compatible with nursing")
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Codeine
Mechanism of action
Narcotic agonist analgesic with antitussive activity, mu receptor agonist
Absorption
Onset: 30-60 min (PO); 10-30 min (IM)
Duration: 4-6 hr
Peak plasma time: 0.5-1 hr
Distribution
Protein bound: 25%
Vd: 3.5 L/kg (PO); 2.6 L/kg (IM)
Metabolism
Prodrug metabolized to morphine by CYP2D6; demethylated/conjugated in liver (undergoes O-demethylation, N-demethylation, and partial conjugation with glucuronic acid)
Elimination
Half-life: 3-4 hr
Excretion: Urine, feces
Pharmacogenomics
10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors
CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
