Aspirin, Butalbital, Caffeine and Codeine

ASCOMP with Codeine is indicated for the management of the symptom complex of tension (or muscle contraction) headache, when non-opioid analgesic and alternative treatments are inadequate. Limitations of Use: Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including ASCOMP with Codeine, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ASCOMP with Codeine should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Butalbital, a barbiturate, is a GABA A receptor agonist and may inhibit excitatory AMPA receptors. Aspirin is a nonsteroidal anti-inflammatory drug and a non-selective irreversible inhibitor of cyclooxygenases. Caffeine is a methylxanthine and CNS stimulant. The exact mechanism with respect to the indication is not clear, however, the effects of caffeine may be due to antagonism of adenosine receptors. Codeine is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.

Periodically reassess patients receiving ASCOMP with Codeine to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with ASCOMP with Codeine, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ASCOMP with Codeine should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals.

ASCOMP with Codeine is contraindicated for: All children younger than 12 years of age Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. ASCOMP with Codeine is also contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. Known or suspected gastrointestinal obstruction, including paralytic ileus Hypersensitivity or intolerance to aspirin, caffeine, butalbital, or codeine.

Boxed warning (serious and life-threatening risks from use of ascomp with codeine): Addiction, Abuse, and Misuse Because the use of ASCOMP with Codeine 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 and reassess all patients regularly for the development of these behaviors and conditions. Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation.

The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Neonatal Opioid Withdrawal Syndrome Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children Opioid-Induced Hyperalgesia and Allodynia Adrenal Insufficiency Severe Hypotension Risks of Use in Patients with Gastrointestinal Conditions Including Peptic Ulcer Disease Increased Risk of Seizures in Patients with Seizure Disorders Withdrawal Coagulation Abnormalities and Bleeding Risks Reye's Syndrome Serious Skin Reactions Allergy Most common adverse reactions (incidence > 1%) are nausea and/or abdominal pain, drowsiness, and dizziness.

Table 1 includes clinically significant drug interactions with ASCOMP with Codeine. Table 1: Clinically Significant Drug Interactions with ASCOMP with Codeine Inhibitors of CYP3A4 Clinical Impact: The concomitant use of ASCOMP with Codeine with CYP3A4 inhibitors may result in an increase in codeine plasma concentrations with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of ASCOMP with Codeine is achieved.

Store and Dispense Store below 25°C (77°F) in a tight, light-resistant container. Protect from moisture. Store ASCOMP with Codeine securely and dispose of properly.