Applies to aspirin / butalbital / caffeine / codeine: oral capsule.
Warning
Oral route (Capsule)
Addiction, Abuse, and Misuse
Butalbital/aspirin/caffeine/codeine phosphate 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 codeine sulfate, 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 butalbital/aspirin/caffeine/codeine phosphate. Monitor for respiratory depression, especially during initiation of butalbital/aspirin/caffeine/codeine phosphate or following a dose increase.
Accidental Ingestion
Accidental ingestion of even one dose of butalbital/aspirin/caffeine/codeine phosphate, especially by children, can result in a fatal overdose of butalbital/aspirin/caffeine/codeine phosphate.
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 butalbital/aspirin/caffeine/codeine phosphate 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.
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. Butalbital/aspirin/caffeine/codeine phosphate 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 butalbital/aspirin/caffeine/codeine phosphate 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 butalbital/aspirin/caffeine/codeine phosphate 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 butalbital/aspirin/caffeine/codeine phosphate requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.
Serious side effects
Along with its needed effects, aspirin/butalbital/caffeine/codeine 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 / butalbital / caffeine / codeine:
Rare
- Back, leg, or stomach pains
- black, tarry stools
- bleeding gums
- blistering, peeling, or loosening of the skin
- bloody urine
- blurred vision
- chest pain or tightness
- chills
- confusion
- cough
- dark urine
- decreased frequency or amount of urine
- diarrhea
- difficulty breathing
- difficulty swallowing
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- fast, irregular, pounding, or racing heartbeat or pulse
- fever
- general tiredness and weakness
- headache
- hives, itching, or skin rash
- increased thirst
- joint or muscle pain
- light-colored stools
- lower back or side pain
- nausea
- nosebleeds
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- red skin lesions, often with a purple center
- red, irritated eyes
- shakiness in the legs, arms, hands, or feet
- sores, ulcers, or white spots in the mouth or on the lips
- sweating
- swelling of the face, fingers, or lower legs
- trembling or shaking of the hands or feet
- upper right abdominal or stomach pain
- vomiting
- vomiting blood
- weight gain
- yellow eyes and skin
Incidence not known
- Agitation
- bloody nose
- confusion
- constricted, pinpoint, or small pupils (black part of the eye)
- darkening of the skin
- loss of appetite
- mental depression
- overactive reflexes
- poor coordination
- restlessness
- seeing, hearing, or feeling things that are not there
- shivering
- trouble sleeping
- twitching
- unusual tiredness or weakness
Get emergency help immediately if any of the following symptoms of overdose occur while taking aspirin / butalbital / caffeine / codeine:
Symptoms of overdose
- Cold and clammy skin
- confusion as to time, place, or person
- continuing ringing or buzzing or other unexplained noise in the ears
- coughing that sometimes produces a pink frothy sputum
- difficult or trouble breathing
- drowsiness
- extremely high fever or body temperature
- hearing loss
- holding false beliefs that cannot be changed by fact
- increased sweating
- irregular, fast or slow, or shallow breathing
- loss of consciousness
- muscle cramps
- pale or blue lips, fingernails, or skin
- pinpoint pupils (black part of the eyes)
- restlessness
- seeing, hearing, or feeling things that are not there
- seizures
- swelling in the legs and ankles
- trouble sleeping
- unusual bleeding or bruising
Other side effects
Some side effects of aspirin / butalbital / caffeine / codeine 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:
Rare
- Anxiety
- blurred vision
- burning, tingling, numbness, or pain in the hands, arms, feet, or legs
- confusion about identity, place, and time
- constricted, pinpoint, or small pupils (black part of the eye)
- deep or fast breathing with dizziness
- depression
- difficulty having a bowel movement
- dry mouth
- feeling of constant movement of self or surroundings
- feeling of warmth
- feeling that others are watching you or controlling your behavior
- feeling that others can hear your thoughts
- heartburn
- high energy
- irregular heartbeat
- irritability
- loss in sexual ability, desire, drive, or performance
- numbness of the feet, hands, and around mouth
- pain in the legs
- redness of the face, neck, arms, and occasionally, upper chest
- sensation of spinning
- severe mood or mental changes
- shaking
- sleepiness
- sluggishness
- slurred speech
- trouble sitting still
- unexplained weight loss
- unusual behavior
- weakness
Incidence not known
- Decreased interest in sexual intercourse
- inability to have or keep an erection
- loss in sexual ability, desire, drive, or performance
For Healthcare Professionals
Applies to aspirin / butalbital / caffeine / codeine: oral capsule.
General
The most common adverse reactions have included nausea and/or abdominal pain, drowsiness, and dizziness.[Ref]
Hypersensitivity
Postmarketing reports: Allergic reaction, anaphylactic shock, anaphylaxis[Ref]
Gastrointestinal
Common (1% to 10%): Nausea/abdominal pain
Uncommon (0.1% to 1%): Dry mouth, vomiting, difficulty swallowing, heartburn
Postmarketing reports: Salivation, anorexia, increased appetite, constipation, diarrhea, esophagitis, gastroenteritis, gastrointestinal spasm, mouth burning, pyloric ulcer, stomach upset[Ref]
Psychiatric
Uncommon (0.1% to 1%): Agitation
Postmarketing reports: Abuse, addiction, anxiety, depression, hallucination, insomnia, libido decreased, nervousness, psychosis, increased sexual activity[Ref]
Nervous system
Common (1% to 10%): Drowsiness, dizziness/lightheadedness, feeling intoxicated
Uncommon (0.1% to 1%): Headache, shaky feeling, tingling, fainting, numbness
Postmarketing reports: Hyperactivity, disorientation, sedation, slurred speech, twitching, unconsciousness
Opioids:
Postmarketing reports: Serotonin syndrome (with concomitant use with serotonergic drugs)[Ref]
Other
Uncommon (0.1% to 1%): Fatigue, heavy eyelids, high energy, hot spells, sluggishness, fever, earache, tinnitus
Postmarketing reports: Vertigo[Ref]
Cardiovascular
Uncommon (0.1% to 1%): Tachycardia
Postmarketing reports: Flushing, chest pain, hypotensive reaction, palpitations, syncope, edema[Ref]
Genitourinary
Uncommon (0.1% to 1%): Diuresis
Postmarketing reports: Urinary difficulty[Ref]
Dermatologic
Uncommon (0.1% to 1%): Hyperhidrosis, pruritus
Postmarketing reports: Erythema, erythema multiforme, exfoliative dermatitis, hives, rash, toxic epidermal necrolysis[Ref]
Renal
Postmarketing reports: Kidney impairment[Ref]
Musculoskeletal
Uncommon (0.1% to 1%): Leg pain, muscle fatigue[Ref]
Respiratory
Uncommon (0.1% to 1%): Nasal congestion
Postmarketing reports: Epistaxis, hiccup[Ref]
Ocular
Postmarketing reports: Miosis[Ref]
Oncologic
Postmarketing reports: Cholangiocarcinoma[Ref]
Endocrine
Opioids:
Postmarketing reports: Adrenal insufficiency, androgen deficiency
