BUTALBITAL, ASPIRIN, CAFFEINE AND CODEINE PHOSPHATE (Page 4 of 11)

5.9 Interaction with Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) may potentiate the effects of morphine, codeine’s active metabolite, including respiratory depression, coma, and confusion. ASCOMP with Codeine should not be used in patients taking MAOIs or within 14 days of stopping such treatment.

5.10 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

5.11 Severe Hypotension

ASCOMP with Codeine may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of ASCOMP with Codeine. In patients with circulatory shock, ASCOMP with Codeine may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of ASCOMP with Codeine in patients with circulatory shock.

5.12 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), ASCOMP with Codeine may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with ASCOMP with Codeine.

Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of ASCOMP with Codeine in patients with impaired consciousness or coma.

5.13 Risks of Use in Patients with Gastrointestinal Conditions Including Peptic Ulcer Disease

ASCOMP with Codeine is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The codeine in ASCOMP with Codeine may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding.

The aspirin in ASCOMP with Codeine can cause GI side effects including stomach pain, heartburn, nausea, vomiting, and gross GI bleeding. Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Physicians should inform patients about the signs and symptoms of GI side effects and what steps to take if they occur.

5.14 Increased Risk of Seizures in Patients with Seizure Disorders

The codeine in ASCOMP with Codeine may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during ASCOMP with Codeine therapy.

5.15 Withdrawal

​ Do not abruptly discontinue ASCOMP with Codeine in a patient physically dependent on opioids. Rapid tapering of butalbital, aspirin, caffeine, and codeine phosphate capsules in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.3), Drug Abuse and Dependence (9.3)].

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including ASCOMP with Codeine. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].

When discontinuing ASCOMP with Codeine in a physically-dependent patient, gradually taper the dosage [see Dosage and Administration (2.3)]. Abrupt discontinuation of butalbital can cause seizures [see Drug Abuse and Dependence (9.3)].

5.16 Risks of Driving and Operating Machinery

ASCOMP with Codeine may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of ASCOMP with Codeine and know how they will react to the medication.

5.17 Coagulation Abnormalities and Bleeding Risks

Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect patients with inherited (i.e. hemophilia) or acquired (i.e. liver disease or vitamin K deficiency) bleeding disorders. Aspirin is contraindicated in patients with hemophilia.

Aspirin administered pre-operatively may prolong the bleeding time.

Patients who consume three or more alcoholic drinks every day should be counseled about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin.

5.18 Reye’s Syndrome

Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye’s syndrome with concomitant use of aspirin in certain viral illnesses.

5.19 Allergy

Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug products (NSAIDs) and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma).

5.20 Drug/Laboratory Test Interactions

Aspirin: Aspirin may interfere with the following laboratory determinations in blood: serum amylase, fasting blood glucose, cholesterol, protein, serum glutamic-oxalacetic transaminase (SGOT), uric acid, prothrombin time and bleeding time. Aspirin may interfere with the following laboratory determinations in urine: glucose, 5-hydroxy-indoleacetic acid, Gerhardt ketone, vanillylmandelic acid (VMA), uric acid, diacetic acid, and spectrophotometric detection of barbiturates.

Codeine: Codeine may increase serum amylase levels.

6 ADVERSE REACTIONS

The following serious adverse reactions are described, or described in greater detail, in other sections:

• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)]
• Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)]
• Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.4)]
• Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see Warnings and Precautions (5.5)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.6)]
• Adrenal Insufficiency [see Warnings and Precautions (5.10)]
• Severe Hypotension [see Warnings and Precautions (5.11)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.13)]
• Seizures [see Warnings and Precautions (5.14)]
• Withdrawal [see Warnings and Precautions (5.15)]
• Coagulation Abnormalities and Bleeding [see Warnings and Precautions (5.17)]
• Reye’s Syndrome [see Warnings and Precautions (5.18)]
• Allergy [see Warnings and Precautions (5.19)]