Applies to codeine / promethazine: oral solution, oral syrup.
Warning
Oral route (Solution)
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 CYP2D6 polymorphism. Promethazine hydrochloride and codeine phosphate oral solution 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 promethazine hydrochloride and codeine phosphate oral solution 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.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.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
Oral route (Syrup)
Promethazine and codeine use is contraindicated in pediatric patients younger than 6 years. Concomitant use of promethazine products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients. Postmarketing cases of respiratory depression, including fatalities, have been reported with a wide range of weight-based promethazine doses in pediatric patients younger than 2 years. Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultrarapid metabolizers of codeine due to CYP2D6 polymorphism. Concomitant use of opioids and benzodiazepines 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.
Serious side effects
Along with its needed effects, codeine / promethazine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking codeine / promethazine:
Incidence not known
- Bluish lips or skin
- chills
- clay-colored stools
- cold sweats
- confusion
- cough
- dark urine
- decrease in the frequency of urination
- decrease in the urine volume
- diarrhea
- difficult or troubled breathing
- difficulty in passing urine (dribbling)
- dizziness
- dizziness, faintness, or lightheadedness when getting up from lying or sitting position
- fast, pounding, or irregular heartbeat or pulse
- feeling of warmth
- fever
- headache
- high fever
- hives or welts, itching, or rash
- increased sweating
- irregular, fast or slow, or shallow breathing
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- loss of appetite
- loss of bladder control
- nausea
- noisy breathing
- not breathing
- painful urination
- pale or blue lips, fingernails, or skin
- rectal bleeding
- redness of the face, neck, arms, and occasionally, upper chest
- redness of the skin
- seeing, hearing, or feeling things that are not there
- seizures
- severe muscle stiffness
- shakiness in the legs, arms, or hands
- stomach pain
- sweating
- tightness in the chest
- tiredness
- trembling or shaking of the hands or feet
- unpleasant breath odor
- unusual tiredness or weakness
- unusually pale skin
- vomiting of blood
- yellow eyes or skin
Get emergency help immediately if any of the following symptoms of overdose occur while taking codeine / promethazine:
Symptoms of overdose
- Cold, clammy skin
- dry mouth
- fainting
- no blood pressure or pulse
- no muscle tone or movement
- pinpoint pupils (black part of the eye)
- stopping of the heart
- unconsciousness
Other side effects
Some side effects of codeine / promethazine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Incidence not known
- Bad dreams
- blurred or loss of vision
- confusion as to time, place, or person
- continuing ringing or buzzing or other unexplained noise in the ears
- difficulty having a bowel movement
- disturbed color perception
- double vision
- drowsiness
- false or unusual sense of well-being
- halos around lights
- hearing loss
- holding false beliefs that cannot be changed by fact
- increased sensitivity of the skin to sunlight
- night blindness
- overbright appearance of lights
- redness or other discoloration of the skin
- relaxed and calm feeling
- severe sunburn
- sleepiness
- trouble sleeping
- tunnel vision
- unusual excitement, nervousness, or restlessness
- vomiting
For Healthcare Professionals
Applies to codeine / promethazine: oral syrup.
General
The more commonly reported adverse effects have included nausea, vomiting, constipation, blurred vision, confusion, and dizziness.[Ref]
Respiratory
Concomitant administration of promethazine with other respiratory depressants has been associated with respiratory depression, including fatalities. Postmarketing cases in pediatric patients less than 2 years of age has been reported with a wide range of weight-based doses. Respiratory depression has been associated with antitussive use of codeine in young children.
Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy. Further investigation has shown these patients to be ultra-rapid metabolizers of codeine. Children with obstructive sleep apnea who are treated with codeine appear to be particularly sensitive to the respiratory depressant effects of codeine.[Ref]
Codeine:
Frequency not reported: Respiratory depression
Promethazine:
Frequency not reported: Asthma, nasal stuffiness, respiratory depression, apnea[Ref]
Nervous system
Codeine
Frequency not reported: CNS depression, lightheadedness, dizziness, sedation, headache, convulsions, weakness
Promethazine:
Frequency not reported: Drowsiness, sedation, somnolence, extra-pyramidal symptoms, torticollis, tongue protrusion, incoordination, tremors, seizures, neuroleptic malignant syndrome, paradoxical reactions[Ref]
Promethazine use has resulted in paradoxical reactions described as hyperexcitability and abnormal movements. This has occurred following 1 dose and in some patients accompanied by respiratory depression, nightmares, delirium, and agitated behavior.[Ref]
Psychiatric
Codeine
Frequency not reported: Euphoria, dysphoria, transient hallucination, disorientation
Promethazine:
Frequency not reported: Confusion, disorientation, euphoria, nervousness, insomnia, excitation, catatonic-like states, hysteria, hallucinations[Ref]
Gastrointestinal
Codeine
Frequency not reported: Nausea, vomiting, constipation, biliary tract spasm, increased colonic motility, toxic dilation
Promethazine:
Frequency not reported: Dry mouth, nausea, vomiting[Ref]
Patients with chronic ulcerative colitis may experience increased colonic motility, while patients with acute ulcerative colitis have experienced toxic dilation with codeine use.[Ref]
Hypersensitivity
Codeine
Frequency not reported: Pruritus, giant urticaria, angioneurotic edema, laryngeal edema
Promethazine:
Frequency not reported: Angioneurotic edema[Ref]
Cardiovascular
Codeine
Frequency not reported: Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension, circulatory depression
Promethazine:
Frequency not reported: Increased or decreased blood pressure, tachycardia, bradycardia, faintness[Ref]
Genitourinary
Codeine
Frequency not reported: Oliguria, urinary retention, antidiuretic effect[Ref]
Dermatologic
Promethazine:
Frequency not reported: Dermatitis, photosensitivity, urticaria[Ref]
Hematologic
Promethazine:
Frequency not reported: Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis[Ref]
Hepatic
Promethazine:
Frequency not reported: Cholestatic jaundice[Ref]
Metabolic
Promethazine:
Frequency not reported: Hyperglycemia
Ocular
Codeine
Frequency not reported: Visual disturbances
Promethazine:
Frequency not reported: Blurred vision, oculogyric crisis, diplopia[Ref]
Other
Promethazine:
Frequency not reported: Lassitude, tinnitus, fatigue[Ref]
