Usual Adult Dose for Headache

1 or 2 capsules orally every 4 hours as needed not to exceed 6 capsules per day

Comments:

• Because of the risks of addiction, abuse, and misuse, prescribing should be reserved to patients for whom alternative options have not been tolerated or are not expected to be tolerated; and for patients for whom alternative options have not provided adequate analgesia or are not expected to provide adequate analgesia.
• The safety and efficacy of treating multiple recurrent headaches with this product is not known.

Uses: For the relief of the symptom complex of tension (or muscle contraction) headache when nonopioid analgesic and alternative treatments are inadequate.

Renal Dose Adjustments

Use with caution

Liver Dose Adjustments

Use with caution

Dose Adjustments

Elderly: Dose selection should be cautious generally starting at the low end of the dosing range.

The drug should not be abruptly discontinued in the physically dependent person.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; and HEPATOTOXICITY:

• Addiction, Abuse, and Misuse: Use of this drug exposes patients and other users to the risks of opioid addiction and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
• Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required 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. Monitor for respiratory depression, especially during initiation or following a dose increase.
• Accidental Ingestion of/exposure to even one dose, especially by children, can result in a fatal overdose.
• Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and 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 CYP450 2D6 polymorphism. This drug 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 this drug 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 can result from prolonged maternal opioid use during pregnancy; it may be life-threatening if not recognized and treated; it should be managed according to protocols developed by neonatology experts. If opioid use is needed for a prolonged period in a pregnant woman, advise patient of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment be available.
• Interactions with Drugs Affecting CYP450 Isoenzymes: The effects of concomitant use or discontinuation of CYP450 3A4 inducers/inhibitors or CYP450 2D6 inhibitors are complex; concomitant use requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.
• Hepatotoxicity: This combination drug contains acetaminophen which has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most cases of liver injury are associated with acetaminophen use at doses that exceed 4000 mg per day, and often involve more than 1 acetaminophen-containing product.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally as needed
• Do not exceed 6 capsules/tablets per day or 180 mL of oral liquid per day; do not exceed 4000 mg of acetaminophen per day; when calculating daily acetaminophen doses, be sure to include all acetaminophen-containing products and all routes of administration.
• Oral liquid is 7.368% alcohol.

Storage requirements: Protect from light and moisture

General:

• Butalbital and codeine are drugs that may be abused; extended use is not recommended.
• Acetaminophen induced hepatotoxicity is mostly preventable by ensuring maximum daily doses are not exceeded; use of more than 1 acetaminophen-containing product at one time should be discouraged as the use of multiple acetaminophen-containing products increases the risk of excess acetaminophen doses.
• Serious skin reaction may occur; discontinue therapy at first appearance of skin rash or any other sign of hypersensitivity.

Monitoring:

• Monitor for potential abuse
• Monitor for respiratory depression and signs of morphine overdose
• Monitor for nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in upper right part of the stomach, yellow of the skin or eyes, and/or flu-like symptoms as this may be an indication of acetaminophen overdose.
• Monitor for skin reactions

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Patients should be advised that this drug has the potential to cause physical and psychological dependence, and tolerance; patients should be instructed to take this drug as prescribed, in the amounts prescribed, and no more frequently than prescribed.
• Patients should understand the risks of life-threatening respiratory depression and when this risk is greatest, patients should be aware that a genetic mutation may result in greater toxicity in some patients.
• Patients should be advised that severe liver damage may occur if more than the recommended amount of acetaminophen is taken; if they suspect they may have taken too much acetaminophen or if they experience nausea, vomiting, loss of appetite, or yellowing of the skin or eyes they should seek medical help promptly.
• Patients should be discouraged from using multiple acetaminophen-containing products concurrently; patients should be instructed to check with their healthcare provider or pharmacist if they have questions on what products contain acetaminophen.
• Patients should be advised to avoid alcohol use while taking this drug.
• Patients should be advised to avoid potentially hazardous tasks such as driving a car while taking this drug.
• Women of childbearing potential should be advised to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.