Applies to acetaminophen / caffeine / dihydrocodeine: oral capsule, oral tablet.
Warning
Oral route (Capsule)
Addiction, Abuse, and Misuse
Acetaminophen/caffeine/dihydrocodeine bitartrate expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing acetaminophen/caffeine/dihydrocodeine bitartrate, and monitor all patients regularly for the development of these behaviors or conditions.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of acetaminophen / caffeine / dihydrocodeine bitartrate. Monitor for respiratory depression, especially during initiation of acetaminophen / caffeine / dihydrocodeine bitartrate or following a dose increase.
Accidental Ingestion
Accidental ingestion of even one dose of acetaminophen / caffeine / dihydrocodeine bitartrate, especially by children, can result in a fatal overdose of acetaminophen / caffeine / dihydrocodeine bitartrate.
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 CYP2D6 polymorphism. Acetaminophen / caffeine / dihydrocodeine bitartrate 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 acetaminophen / caffeine / dihydrocodeine bitartrate 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.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of acetaminophen / caffeine / dihydrocodeine bitartrate during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Interactions with Drug Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with acetaminophen / caffeine / dihydrocodeine bitartrate requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product.
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of acetaminophen / caffeine / dihydrocodeine bitartrate and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
Serious side effects
Along with its needed effects, acetaminophen / caffeine / dihydrocodeine 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 acetaminophen / caffeine / dihydrocodeine:
More common
- Bleeding gums
- blood in the urine or stools
- bloody, black, or tarry stools
- chest pain
- chills
- clay colored stools
- cough
- dark urine
- decreased appetite
- dizziness
- drowsiness
- fever
- headache
- high fever
- itching or skin rash
- lightheadedness
- loss of appetite
- nausea
- painful or difficult urination
- pale skin
- pinpoint red spots on the skin
- sore throat
- sores, ulcers, or white spots on the lips or in the mouth
- stomach pain or tenderness
- swelling of the feet or lower legs
- swollen glands
- unexplained or unusual bleeding or bruising
- unusual tiredness or weakness
- vomiting
- yellow eyes or skin
Rare
- Agitation
- confusion
- decreased urine output
- difficulty with swallowing
- fast heartbeat
- hives
- hostility
- irritability
- loss of consciousness
- muscle twitching
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- rapid weight gain
- seeing, hearing, or feeling things that are not there
- seizures
- stupor
- swelling of the face, ankles, or hands
- tightness in the chest
- unusual drowsiness, dullness, or feeling of sluggishness
Incidence not known
- Cold sweats
- darkening of the skin
- decrease in the frequency of urination
- decrease in the urine volume
- difficult or troubled breathing
- difficulty in passing urine (dribbling)
- dizziness, faintness, or lightheadedness when getting up from lying or sitting position
- fainting
- irregular, fast or slow, or shallow breathing
- overactive reflexes
- pale or blue lips, fingernails, or skin
- poor coordination
- shivering
- talking or acting with excitement you cannot control
- trembling or shaking
Other side effects
Some side effects of acetaminophen / caffeine / dihydrocodeine 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
- Difficulty having a bowel movement
- relaxed and calm feeling
- sleepiness
Incidence not known
- Constricted, pinpoint, or small pupils (black part of the eye)
- diarrhea
- dry mouth
- gas in the stomach
- heartburn
For Healthcare Professionals
Applies to acetaminophen / caffeine / dihydrocodeine: oral capsule, oral tablet.
General
The most frequently expected adverse reactions based on the individual components may include lightheadedness, dizziness, drowsiness, sedation, nausea, vomiting, constipation, pruritus and skin reactions.[Ref]
Hepatic
Acetaminophen:
Frequency not reported: Hepatotoxicity[Ref]
Respiratory
Dihydrocodeine:
Frequency not reported: Respiratory depression, cough suppression[Ref]
Psychiatric
Dihydrocodeine:
Frequency not reported: Confusion, physical and psychological dependence, hallucinations vivid dreams
Caffeine:
Frequency not reported: Anxiety, anxiety neurosis, excitement, insomnia, irritability, restlessness, tenseness[Ref]
Dermatologic
Dihydrocodeine:
Frequency not reported: Sweating, pruritus, skin reactions
Acetaminophen:
Rare (less than 0.1%): Serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN)
Caffeine:
Frequency not reported: Urticaria[Ref]
Hypersensitivity
Dihydrocodeine:
Frequency not reported: Anaphylactoid reactions, hypersensitivity reactions
Acetaminophen:
Rare (less than 0.1%): Anaphylactoid reactions
Frequency not reported: Hypersensitivity reactions including urticarial or erythematous skin reactions, laryngeal edema, angioedema[Ref]
Nervous system
Postmarketing reports: Serotonin syndrome
Dihydrocodeine:
Rare (less than 0.1%): Narcosis
Frequency not reported: Lightheadedness, dizziness, drowsiness, sedation, headache
Caffeine:
Frequency not reported: Headaches, lightheadedness, tremor[Ref]
Renal
Dihydrocodeine:
Rare (less than 0.1%): Acute renal failure
Frequency not reported: Granulomatous interstitial nephritis
Caffeine:
Frequency not reported: Diuresis[Ref]
Cardiovascular
Dihydrocodeine:
Frequency not reported: Orthostatic hypotension
Caffeine:
Frequency not reported: Extrasystoles, palpitations, tachycardia[Ref]
Endocrine
Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis and lead to androgen deficiency; however, the causal role of opioids is unknown due to the lack of studies into the many medical, physical, lifestyle, and psychological stressors that influence gonadal hormone levels.[Ref]
Postmarketing reports: Adrenal insufficiency
Opioids:
Frequency not reported: Androgen deficiency[Ref]
Gastrointestinal
Dihydrocodeine:
Frequency not reported: Nausea, vomiting, constipation, abdominal pain, diarrhea, dry mouth, indigestion, spasm of biliary tract
Caffeine:
Frequency not reported: Diarrhea, nausea, stomach pain, vomiting[Ref]
Genitourinary
Dihydrocodeine:
Frequency not reported: Urinary retention[Ref]
Hematologic
Acetaminophen:
Frequency not reported: Thrombocytopenia, leukopenia, pancytopenia, neutropenia, thrombocytopenic purpura, agranulocytosis[Ref]
Metabolic
Dihydrocodeine:
Frequency not reported: Anorexia[Ref]
Ocular
Dihydrocodeine:
Frequency not reported: Miosis
Caffeine:
Frequency not reported: Scintillating scotoma[Ref]
Other
Dihydrocodeine:
Frequency not reported: Fatigue
Caffeine:
Frequency not reported: Tinnitus[Ref]
