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Drug Interactions between clozapine and Complete Acid Reducer plus Antacid

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

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Interactions between your drugs

Moderate

famotidine cloZAPine

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and clozapine

MONITOR: Famotidine may cause QTc prolongation. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. According to the manufacturer, prolongation of the QT interval has been reported very rarely in patients with impaired renal function whose dose/dosing interval of famotidine may not have been adjusted appropriately. In general, the risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution and clinical monitoring are recommended if famotidine is used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. "Product Information. Pepcid (famotidine)." Merck & Co., Inc PROD (2002):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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Moderate

cloZAPine magnesium hydroxide

Applies to: clozapine and Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide)

MONITOR: Bowel cleansing as well as overuse of certain laxatives may cause electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia in patients treated with drugs that prolong the QT interval. Electrolyte disturbances including hypokalemia and hypomagnesemia have been reported with laxative abuse and are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Patients treated with drugs that prolong the QT interval should exercise caution when self-medicating with laxatives. The recommended dosage and duration of use should not be exceeded. Patients treated with lactulose for more than six months should be monitored periodically for electrolyte imbalance. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Chin RL "Laxative-induced hypokalemia." Ann Emerg Med 32 (1998): 517-8
  2. Muller-Lissner SA "Adverse effects of laxatives: fact and fiction." Pharmacology 47 (1993): 138-45
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Schaefer DC, Cheskin LJ "Constipation in the elderly." Am Fam Physician 58 (1998): 907-14
View all 6 references

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Minor

famotidine calcium carbonate

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and Complete Acid Reducer plus Antacid (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

famotidine magnesium hydroxide

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and Complete Acid Reducer plus Antacid (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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Drug and food interactions

Moderate

cloZAPine food

Applies to: clozapine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Moderate

calcium carbonate food

Applies to: Complete Acid Reducer plus Antacid (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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Minor

cloZAPine food

Applies to: clozapine

Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.

References

  1. Carrillo JA, Jerling M, Bertilsson L "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol 15 (1995): 376-7
  2. Odom-White A, de Leon J "Clozapine levels and caffeine." J Clin Psychiatry 57 (1996): 175-6
  3. Vainer JL, Chouinard G "Interaction between caffeine and clozapine." J Clin Psychopharmacol 14 (1994): 284
  4. Hagg S, Spiset O, Mjorndal T, Dalqvist R "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol 49 (2000): 59-63
View all 4 references

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Minor

famotidine food

Applies to: Complete Acid Reducer plus Antacid (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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