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Drug Interactions between aspirin / calcium carbonate and Nizoral

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

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Interactions between your drugs

Moderate

ketoconazole calcium carbonate

Applies to: Nizoral (ketoconazole) and aspirin / calcium carbonate

ADJUST DOSING INTERVAL: The dissolution of oral ketoconazole requires an acidic environment. Medications that decrease the acidity of the stomach, such as omeprazole or H2 antagonists can reduce the bioavailability of ketoconazole by 75% to 80%. Antacids are also expected to impair ketoconazole absorption. Levoketoconazole, which is an enantiomer of ketoconazole is expected to have similar interactions.

MANAGEMENT: It is recommended to administer antacids at least 1 hour before or 2 hours after ketoconazole. Patients should be monitored for altered antifungal effects and the ketoconazole dosage adjusted if necessary. Levoketoconazole manufacturer recommends administering antacids at least 2 hours after taking levoketoconazole. Patients should be monitored for diminished levoketoconazole effects.

References

  1. Brass C, Galgiani JN, Blaschke TF, et al. "Disposition of ketoconazole, an oral antifungal, in humans." Antimicrob Agents Chemother 21 (1982): 151-8
  2. Van der Meer JW, Keuning JJ "The influence of gastric acidity on the bio-availability of ketoconazole." J Antimicrob Chemother 6 (1980): 552-4
  3. Carlson JA, Mann HJ, Canafax DM "Effect of pH on disintegration and dissolution of ketoconazole tablets." Am J Hosp Pharm 40 (1983): 1334-6
  4. Chin TWF, Loeb M, Fong IW "Effects of an acidic beverage (coca-cola) on absorption of ketoconazole." Antimicrob Agents Chemother 39 (1995): 1671-5
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
  7. Cerner Multum, Inc "ANVISA Bulário Eletrônico." O 0 (2015):
  8. "Product Information. Ketoconazole (ketoconazole)." Mylan Pharmaceuticals Inc (2019):
View all 8 references

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Moderate

aspirin calcium carbonate

Applies to: aspirin / calcium carbonate and aspirin / calcium carbonate

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

References

  1. D'Arcy PF, McElnay JC "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm 21 (1987): 607-17
  2. Gaspari F, Vigano G, Locatelli M, Remuzzi G "Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis." Am J Kidney Dis 11 (1988): 338-42
  3. Furst DE "Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications." J Rheumatol Suppl 17 (1988): 58-62
  4. Miners JO "Drug interactions involving aspirin (acetylsalicylic acid) and salicylic acid." Clin Pharmacokinet 17 (1989): 327-44
  5. Levy G, Lampman T, Kamath BL, Garrettson LK "Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid." N Engl J Med 293 (1975): 323-5
  6. Shastri RA "Effect of antacids on salicylate kinetics." Int J Clin Pharmacol Ther Toxicol 23 (1985): 480-4
  7. Covington TR, eds., Lawson LC, Young LL "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association (1993):
  8. Brouwers JRBJ, Desmet PAGM "Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs." Clin Pharmacokinet 27 (1994): 462-85
  9. "Product Information. Diflunisal (diflunisal)." Chartwell RX, LLC. (2023):
View all 9 references

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Drug and food interactions

Moderate

ketoconazole food

Applies to: Nizoral (ketoconazole)

GENERALLY AVOID: Excessive use of alcohol or products containing alcohol together with ketoconazole or levoketoconazole may potentiate the risk of liver injury. Serious hepatotoxicity has been reported with levoketoconazole. Hepatotoxicity requiring liver transplantation has been reported with the use of oral ketoconazole, of which levoketoconazole is an enantiomer. Some patients had no obvious risk factors for liver disease. In addition, use of alcohol or products containing alcohol during ketoconazole or levoketoconazole therapy may result in a disulfiram-like reaction in some patients. Symptoms of disulfiram-like reaction include flushing, rash, peripheral edema, nausea, and headache.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of ketoconazole or levoketoconazole. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

When administered to healthy volunteers with a high-fat meal (875 calories; 62% fat), levoketoconazole systemic exposure (AUC) increased by 30% while peak plasma concentration (Cmax) did not change and the time to reach Cmax (Tmax) was delayed from 2 to 4 hours, compared to fasted conditions.

MANAGEMENT: Levoketoconazole may be administered with or without food. Excessive consumption of alcohol should generally be avoided during ketoconazole or levoketoconazole therapy. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during ketoconazole or levoketoconazole therapy. Patients receiving ketoconazole or levoketoconazole should be instructed to contact their doctor immediately if they experience swelling, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark colored urine, light colored stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage.

References

  1. "Product Information. Ketoconazole (ketoconazole)." Mylan Pharmaceuticals Inc (2019):
  2. "Product Information. Recorlev (levoketoconazole)." Xeris Pharmaceuticals Inc (2022):
  3. Auchus R, Pivonello R, Fleseriu M, et al. "Levoketoconazole: a novel treatment for endogenous Cushing's syndrome. https://www.tandfonline.com/doi/pdf/10.1080/17446651.2021.1945440" (2022):
  4. "Product Information. Ketoconazole (ketoconazole)." Burel Pharmaceuticals Inc (2021):
View all 4 references

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Moderate

calcium carbonate food

Applies to: aspirin / calcium carbonate

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

aspirin food

Applies to: aspirin / calcium carbonate

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Minor

aspirin food

Applies to: aspirin / calcium carbonate

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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.


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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.