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Drug Interactions between Pepcid Complete and Sublocade

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

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Interactions between your drugs

Moderate

famotidine buprenorphine

Applies to: Pepcid Complete (calcium carbonate / famotidine / magnesium hydroxide) and Sublocade (buprenorphine)

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

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Moderate

buprenorphine magnesium hydroxide

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

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Minor

famotidine calcium carbonate

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

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Minor

famotidine magnesium hydroxide

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

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Drug and food interactions

Major

buprenorphine food

Applies to: Sublocade (buprenorphine)

GENERALLY AVOID: Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

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. 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. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction. 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.

References

  1. (2002) "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc
  2. Kilicarslan T, Sellers EM (2000) "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry, 157, p. 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P (1998) "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction, 93, p. 1385-92
  4. Tracqui A, Kintz P, Ludes B (1998) "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol, 22, p. 430-4
  5. Reynaud M, Tracqui A, Petit G, Potard D, Courty P (1998) "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry, 155, p. 448-9
  6. Kintz P (2002) "A new series of 13 buprenorphine-related deaths." Clin Biochem, 35, p. 513-6
  7. Martin HA (2011) "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs, 37, p. 200-2
  8. Hakkinen M, Launiainen T, Vuori E, Ojanpera I (2012) "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol, 68, p. 301-9
  9. Substance Abuse and Mental Health Services Administration (US) (2013) Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 http://www.ncbi.nlm.nih.gov/books/NBK64245/
  10. Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ (2013) "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend, 132, p. 580-6
  11. Ferrant O, Papin F, Clin B, et al. (2011) "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int, 204, e8-11
  12. Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I (2004) "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction, 99, p. 978-88
  13. Kintz P (2001) "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int, 121, p. 65-9
  14. Sekar M, Mimpriss TJ (1987) "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia, 42, p. 567-8
  15. Gueye PN, Borron SW, Risede P, et al. (2002) "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci, 65, p. 107-14
  16. US Food and Drug Administration (2016) FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf
View all 16 references

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Moderate

calcium carbonate food

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

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Minor

famotidine food

Applies to: Pepcid 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 (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 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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