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Drug Interactions between clonazepam and Dual-Action Acid Controller Complete

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Minor

famotidine calcium carbonate

Applies to: Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide) and Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References

  1. Donn KH, Eshelman FN, Plachetka JR, et al. "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy 4 (1984): 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol 26 (1984): 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol 24 (1987): 551-3
  4. Bodemar G, Norlander B, Walan A "Diminished absorption of cimetidine caused by antacids." Lancet 02/24/79 (1979): 444-5
  5. Steinberg WM, Lewis JH, Katz DM "Antacids inhibit absorption of cimetidine." N Engl J Med 307 (1982): 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol 29 (1989): 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci 29 (1984): 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm 20 (1986): 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol 32 (1987): 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J 285 (1982): 998-9
  11. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol 29 (1994): 14-9
View all 12 references

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Minor

clonazePAM calcium carbonate

Applies to: clonazepam and Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

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.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth 48 (1976): 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry 134 (1977): 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther 24 (1978): 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther 24 (1978): 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther 31 (1982): 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther 19 (1976): 234-9
View all 9 references

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Minor

famotidine magnesium hydroxide

Applies to: Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide) and Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References

  1. Donn KH, Eshelman FN, Plachetka JR, et al. "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy 4 (1984): 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol 26 (1984): 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol 24 (1987): 551-3
  4. Bodemar G, Norlander B, Walan A "Diminished absorption of cimetidine caused by antacids." Lancet 02/24/79 (1979): 444-5
  5. Steinberg WM, Lewis JH, Katz DM "Antacids inhibit absorption of cimetidine." N Engl J Med 307 (1982): 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol 29 (1989): 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci 29 (1984): 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm 20 (1986): 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol 32 (1987): 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J 285 (1982): 998-9
  11. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol 29 (1994): 14-9
View all 12 references

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Minor

clonazePAM magnesium hydroxide

Applies to: clonazepam and Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

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.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth 48 (1976): 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry 134 (1977): 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther 24 (1978): 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther 24 (1978): 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther 31 (1982): 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther 19 (1976): 234-9
View all 9 references

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Drug and food interactions

Moderate

calcium carbonate food

Applies to: Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  5. Mangels AR "Bone nutrients for vegetarians." Am J Clin Nutr 100 (2014): epub
  6. Davies NT "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc 38 (1979): 121-8
View all 6 references

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Moderate

clonazePAM food

Applies to: clonazepam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol 11 (1977): 345-9
  2. Whiting B, Lawrence JR, Skellern GG, Meier J "Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide." Br J Clin Pharmacol 7 (1979): 95-100
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB "Alprazolam pharmacokinetics in alcoholic liver disease." J Clin Pharmacol 24 (1984): 113-9
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI "Pharmacokinetic noninteraction of triazolam and ethanol." J Clin Psychopharmacol 4 (1984): 106-7
  6. Staak M, Raff G, Nusser W "Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol." Int J Clin Pharmacol Biopharm 17 (1979): 205-12
  7. Nichols JM, Martin F, Kirkby KC "A comparison of the effect of lorazepam on memory in heavy and low social drinkers." Psychopharmacology (Berl) 112 (1993): 475-82
View all 7 references

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Minor

famotidine food

Applies to: Dual-Action Acid Controller Complete (calcium carbonate / famotidine / magnesium hydroxide)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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