Applies to codeine / phenylephrine / promethazine: oral elixir, oral syrup.
Warning
Oral route (Solution)
Warning: Addiction, Abuse, and Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children; Promethazine and Respiratory Depression in Children; Medication Errors; Interactions with Drugs Affecting Cytochrome P450 Isoenzymes; Concomitant Use with Benzodiazepines or Other CNS Depressants; Neonatal Opioid Withdrawal Syndromepromethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor closely for these behaviors and conditions.Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation o when used in patients at higher risk.Accidental ingestion of promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution, especially by children, can result in a fatal overdose of codeine.Life-threatening respiratory depression and death have occurred in children who received codeine; most cases followed 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/phenylephrine hydrochloride/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/phenylephrine hydrochloride/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.Ensure accuracy when prescribing, dispensing, and administering promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution. Dosing errors can result in accidental overdose and death.The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor.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 the use of promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution in patients taking benzodiazepines, other CNS depressants, or alcohol.Promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution n is not recommended for use in pregnant women. Prolonged use of promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If promethazine hydrochloride/phenylephrine hydrochloride/codeine phosphate oral solution is used for a prolonged period in a pregnant woman, advise the patient o f the risk o f neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Serious side effects
Along with its needed effects, codeine/phenylephrine/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 / phenylephrine / promethazine:
Incidence not known
- Black, tarry stools
- bleeding gums
- bloating
- blood in the urine or stools
- blurred vision
- chest pain
- chills
- clay-colored stools
- cold sweats
- confusion
- constipation
- cough
- dark urine
- decrease in the frequency of urination
- decrease in urine volume
- difficult or troubled breathing
- difficulty in passing urine (dribbling)
- dizziness
- dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
- fainting
- fast or slow, pounding, or irregular heartbeat or pulse
- fever
- headache
- high fever
- increased sweating
- irregular, fast or slow, or shallow breathing
- lightheadedness
- loss of appetite
- loss of bladder control
- nausea
- nervousness
- painful or difficult urination
- pale or blue lips, fingernails, or skin
- pinpoint red spots on the skin
- pounding in the ears
- rash or itching
- seizures
- severe muscle stiffness
- shakiness in the legs, arms, hands, or feet
- sore throat
- sores, ulcers, or white spots on the lips or in the mouth
- stomach pain
- swollen glands
- tiredness
- trembling or shaking of the hands or feet
- unpleasant breath odor
- unusual bleeding or bruising
- unusual tiredness or weakness
- unusually pale skin
- vomiting
- vomiting of blood
- yellow eyes or skin
Other side effects
Some side effects of codeine / phenylephrine / 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:
More common
- Drowsiness
Incidence not known
- Anxiety
- blurred or loss of vision
- confusion about identity, place, and time
- disturbed color perception
- double vision
- dry mouth
- false or unusual sense of well-being
- halos around lights
- increased sensitivity of the skin to sunlight
- night blindness
- overbright appearance of lights
- redness or other discoloration of the skin
- relaxed and calm feeling
- restlessness
- seeing, hearing, or feeling things that are not there
- severe sunburn
- sleepiness or unusual drowsiness
- trouble sleeping
- tunnel vision
For Healthcare Professionals
Applies to codeine / phenylephrine / promethazine: oral syrup.
General
The more commonly reported adverse effects have included nausea, vomiting, constipation, blurred vision, confusion, and dizziness.[Ref]
Respiratory
Codeine:
Frequency not reported: Respiratory depression
Phenylephrine:
Frequency not reported: Respiratory distress
Promethazine:
Frequency not reported: Asthma, nasal stuffiness, respiratory depression, apnea[Ref]
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]
Cardiovascular
Ischemia with risk of gangrene or thrombosis of compromised vascular may result with phenylephrine use.[Ref]
Codeine:
Frequency not reported: Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension, circulatory depression
Phenylephrine:
Frequency not reported: Ischemia
Promethazine:
Frequency not reported: Increased or decreased blood pressure, tachycardia,
bradycardia, faintness[Ref]
Nervous system
Codeine:
Frequency not reported: CNS depression, lightheadedness, dizziness, sedation, headache, convulsions, weakness
Phenylephrine:
Frequency not reported: Restlessness, dizziness, tremor, 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
Phenylephrine:
Frequency not reported: Anxiety, nervousness
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
Patients with chronic ulcerative colitis may experience increased colonic motility, while patients with acute ulcerative colitis have experienced toxic dilation with codeine use.
Promethazine:
Frequency not reported: Dry mouth, nausea, vomiting[Ref]
Hypersensitivity
Codeine:
Frequency not reported: Pruritus, giant urticaria, angioneurotic edema, laryngeal edema
Promethazine:
Frequency not reported: Angioneurotic edema
Sodium Metabisulfite:
Frequency not reported: Anaphylaxis[Ref]
The syrup contains sodium metabisulfite, a sulfite that may cause allergic-type reactions in susceptible people. Allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes are possible.[Ref]
Other
Phenylephrine:
Frequency not reported: Pain
Promethazine:
Frequency not reported: Lassitude, tinnitus, fatigue[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[Ref]
Ocular
Codeine:
Frequency not reported: Visual disturbances
Promethazine:
Frequency not reported: Blurred vision, oculogyric crisis, diplopia[Ref]
