Drug Interactions between Chlordinium and Polycitra

CONTRAINDICATED: The following interaction does not apply to all products containing potassium citrate. It is applicable to certain oral solid formulations of potassium citrate used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium citrate. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride and potassium citrate at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of oral solid formulations of potassium citrate is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium citrate should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

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A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.

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