Drug Interactions between aspirin / butalbital / caffeine / codeine and bisacodyl / polyethylene glycol 3350 / potassium chloride / sodium bicarbonate / sodium chloride

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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ADJUST DOSING INTERVAL: By increasing gastric pH, antacids may reduce the resistance of the enteric coating of bisacodyl tablets, resulting in earlier release of bisacodyl and gastric irritation and dyspepsia.

MANAGEMENT: The administration of antacids and bisacodyl should be separated by at least one hour.

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GENERALLY AVOID: Concomitant use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) may increase the risk of serious gastrointestinal adverse effects associated with certain osmotic laxatives (e.g., polyethylene glycol (PEG), oral sulfate solution), such as colonic mucosal ulcerations or ischemic colitis. There have been isolated case reports of ischemic colitis occurring with the use of PEG-based bowel cleansing products in combination with higher dosages of bisacodyl (usually greater than 10 mg). Bisacodyl can cause colonic ischemia due to transient reduction in splanchnic blood flow. When administered in conjunction with an osmotic laxative such as PEG, increased intramural pressure secondary to increased peristalsis may lead to ischemic colitis and perforation.

MANAGEMENT: The manufacturers for some osmotic bowel cleansing products recommend avoiding the concurrent use of stimulant laxatives. However, stimulant laxatives, in particular bisacodyl and sodium picosulfate, are sometimes used with PEG in certain bowel cleansing regimens to help reduce dose volume and improve patient tolerability and acceptance. Please consult individual product labeling for specific recommendations and guidance. Patients using osmotic bowel cleansing products and stimulant laxatives who present with sudden abdominal pain, rectal bleeding, or other symptoms of ischemic colitis should be evaluated promptly.

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One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

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