Clorazepate Antacids

Clorazepate, a prodrug, is converted to desmethyldiazepam in the stomach through a pH-dependent process that may be impaired by concurrent antacid use. Several other BZs are also converted to desmethyldiazepam, which has a long half-life and can accumulate, especially in the elderly and those with impaired oxidation. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Although antacids can moderately change the rate of absorption of chlordiazepoxide, clorazepate and diazepam, no adverse interaction of clinical importance has been reported. 

The delay in the absorption of ehlordiazepoxide and diazepam is attributed to the effeet of the antaeid on gastrie emptying. Clorazepate on the other hand is a prodrug, whieh needs aeid eonditions in the stomach for conversion by hydrolysis and deearboxylation to its aetive form. Antacids are presumed to inhibit this eonversion by raising the pH of the stomach contents. ... 

Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS. Steacfy-state plasma desmediyldiazepam during long-term clorazepate use effect of antacids. Clin Pharmacol Ther( 9 T) 31,180-3. 

Chun AHC, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD. Effect of antacids on absorption of clorazepate. Clin Pharmacol Ther (1977) 22, 329-35. 

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See also in sourсe #XX -- [ ]

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