Aspirin / Caffeine / Dihydrocodeine Dosage

Usual Adult Dose for Pain

2 capsules orally every 4 hours as needed

Comment:

• Individualize therapy taking into account patients pain severity, prior analgesic treatment experiences, and risk factors for addiction, abuse, and misuse.
• Because of the risks of addiction, abuse, and misuse, even with recommended doses, reserve use for those whom alternative options have not been tolerated or are not expected to be tolerated, or have not provided adequate analgesia or expected to provide adequate analgesia.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Renal Dose Adjustments

Mild to severe renal impairment (CrCl 10 mL/min or greater): Use with caution
Severe renal impairment (CrCl less than 10 mL/min): Avoid use

Liver Dose Adjustments

Mild to moderate hepatic impairment: Use with caution
Severe hepatic impairment: Avoid use

Dose Adjustments

Use with caution in elderly patients.

Use with caution in patients with biliary tract disease including pancreatitis.

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

• Taper gradually by 25% to 50% every 2 to 4 days while monitoring carefully for signs and symptoms of withdrawal
• If signs or symptoms of withdrawal develop, raise the dose to the previous level and taper more slowly

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; ULTRA-RAPID METABOLISM OF DIHYDROCODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:

• Addiction, Abuse, and Misuse: 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.
• Ultra-Rapid Metabolism of Dihydrocodeine 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 dihydrocodeine.
• 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, dihydrocodeine, and the active metabolite, dihydromorphine.
• 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.

Safety and efficacy have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally with food or a full glass of water to minimize GI distress

Storage requirements:

• Protect from light and moisture

General:

• Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Monitoring:

• Monitor for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after dose increases
• Monitor for signs of orthostatic hypotension, especially in those whose blood pressure is already compromised
• Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia
• Monitor for signs of addiction, abuse or misuse

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 understand that this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression and when this risk is greatest. They should know that a genetic mutation may result in greater toxicity in some patients.
• Patients should be advised to check with their pharmacist or healthcare provider before starting or stopping any medications, including over the counter products and supplements.
• Patients should understand that this drug contains aspirin; they should report any signs and symptoms of unexpected bleeding.
• Patients should be instructed not to drive or operate heavy machinery until they know how this drug effects them.
• Patients should be advised not to drink alcohol or take other CNS depressants with this drug.
• Patients should be advised to store this drug safely out of the sight and reach of children; patients should be instructed in proper disposal.
• Women who are pregnant or are planning to become pregnant should discuss this with their healthcare provider.

Further information

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

Medical Disclaimer