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Aspirin / caffeine / dihydrocodeine Side Effects

For the Consumer

Applies to aspirin/caffeine/dihydrocodeine: oral capsule

Warning

Oral route (Capsule)

Addiction, Abuse, and Misuse

Aspirin/caffeine/dihydrocodeine bitartrate exposes 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 aspirin / caffeine / dihydrocodeine bitartrate, and monitor all patients regularly for the development of these behaviors or conditions.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS 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.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of aspirin / caffeine / dihydrocodeine bitartrate. Monitor for respiratory depression, especially during initiation of aspirin / caffeine / dihydrocodeine bitartrate or following a dose increase.

Accidental Ingestion

Accidental ingestion of even one dose of aspirin / caffeine / dihydrocodeine bitartrate, especially by children, can result in a fatal overdose of aspirin / 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. Aspirin / 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 aspirin / 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 aspirin / 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 CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of CYP3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with aspirin / caffeine / dihydrocodeine bitartrate requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.

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 aspirin / 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.

Along with its needed effects, aspirin / 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 aspirin / caffeine / dihydrocodeine:

Incidence Not Known

  • Agitation
  • anxiety
  • bleeding gums
  • bloating
  • bloody or black, tarry stools
  • bloody or cloudy urine
  • blue lips and fingernails
  • blurred vision
  • chest pain or discomfort
  • chills
  • cold sweats
  • confusion
  • constipation
  • continuing ringing or buzzing or other unexplained noise in the ears
  • cool, pale skin
  • coughing that sometimes produces a pink frothy sputum
  • dark urine
  • darkening of the skin
  • depression
  • diarrhea
  • difficult, fast, noisy breathing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • drowsiness
  • dry mouth
  • fast, pounding, or irregular heartbeat or pulse
  • fast, slow, or irregular heartbeat
  • fever
  • flushed, dry skin
  • fruit-like breath odor
  • general tiredness and weakness
  • greatly decreased frequency of urination or amount of urine
  • headache
  • headache, sudden and severe
  • hearing loss
  • heartburn
  • increased hunger
  • increased sweating
  • increased thirst
  • increased urination
  • indigestion
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
  • light-colored stools
  • loss of appetite
  • loss of consciousness
  • muscle cramps, spasms, pain, weakness, or stiffness
  • muscle tremors
  • nausea
  • nervousness
  • nightmares
  • numbness and tingling of the face, lips, hands, and feet
  • overactive reflexes
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • pinpoint red spots on the skin
  • poor coordination
  • rapid, deep breathing
  • restlessness
  • seizures
  • severe stomach pain
  • shakiness
  • shivering
  • skin rash
  • slurred speech
  • stomach pain, cramping, or burning
  • sunken eyes
  • swelling in the legs, feet, or ankles
  • trembling or shaking
  • trouble with breathing
  • twitching
  • unexplained weight loss
  • unusual bleeding or bruising
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
  • upper right abdominal pain
  • vomiting
  • vomiting of blood or material that looks like coffee grounds
  • vomiting, severe or continuous
  • weakness or heaviness of the legs
  • wrinkled skin
  • yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking aspirin / caffeine / dihydrocodeine:

Symptoms of Overdose

  • Extreme sleepiness
  • irregular, fast or slow, or shallow breathing

Some side effects of aspirin / 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:

Incidence Not Known

  • Belching
  • clumsiness
  • low body temperature
  • sleepiness
  • weak or feeble pulse
  • weight gain

For Healthcare Professionals

Applies to aspirin / caffeine / dihydrocodeine: oral capsule

General

The most frequently expected adverse reactions based on the individual components include lightheadedness, dizziness, drowsiness, sedation, nausea, vomiting, constipation, pruritus and skin reactions.[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]

Hypersensitivity

Dihydrocodeine:

Frequency not reported: Anaphylactoid reactions, hypersensitivity reactions[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

Caffeine:

Frequency not reported: Urticaria[Ref]

Cardiovascular

Dihydrocodeine:

Frequency not reported: Orthostatic hypotension

Caffeine:

Frequency not reported: Extrasystoles, palpitations, tachycardia[Ref]

Endocrine

Opioids:

Frequency not reported: Adrenal insufficiency, androgen deficiency[Ref]

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]

Genitourinary

Dihydrocodeine:

Frequency not reported: Urinary retention[Ref]

Metabolic

Dihydrocodeine:

Frequency not reported: Anorexia[Ref]

Nervous system

Dihydrocodeine:

Rare (less than 0.1%): Narcosis

Frequency not reported: Lightheadedness, dizziness, drowsiness, sedation, headache

Caffeine:

Frequency not reported: Headaches, lightheadedness, tremor

Opioids:

Frequency not reported: Serotonin syndrome[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]

Renal

Dihydrocodeine:

Rare (less than 0.1%): Acute renal failure

Frequency not reported: Granulomatous interstitial nephritis

Caffeine:

Frequency not reported: Diuresis[Ref]

References

1. "Product Information. Synalgos-DC (aspirin / caffeine / dihydrocodeine (ASA/caffeine/dihydrocodeine))." Sun Pharmaceutical Industries, Cranbury, NJ.

2. "Product Information. Trezix (acetaminophen/caffeine/dihydrocodeine)." WraSer Pharmaceuticals, Madison, MS.

3. US Food and Drug Administration "Opioid Pain Medicines: Drug Safety Communication - New Safety Warnings Added to Prescription Opioid Medications. Available from: URL: http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm491715.htm." ([2016, Mar 22]):

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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