Combinations 1.

Antacids + Bisacodyl

2. Antacids + Ketoconazole

3. Antacids + Aspirin

4. Ferrous Sulfate + Tetracycline

5. Ferrous Sulfate + Ciprofloxacin

Rationale Bisacodyl-containing products recommend that antacids or dairy products not be taken within 1 hour prior to taking bisacodyl. Delayedrelease bisacodyl tablets are designed to release drug in the large intestine, and products that decrease the acidity in the stomach may cause these tablets to release bisacodyl early, possibly leading to gastric irritation and/or cramps. The absorption of ketoconazole was reduced by approximately 95% in 3 healthy volunteers when administered 2 hours after a dose of oral sodium bicarbonate. According to ketoconazole prescribing information, ketoconazole tablets require an acidic environment for dissolution. Antacids, via their ability to produce more alkaline urine, can increase the urinary excretion of salicylates. The salicylates, as acidic compounds, exist in an ionized form when in alkaline environments. This form of the compound is not easily reabsorbed in the kidney and is thus eliminated in the urine. The urinary excretion of aspirin has been shown to be significantly correlated with urinary pH, with increased excretion associated with increases in urine pH. Tetracycline absorption was decreased by 81% when coadministered with ferrous sulfate. Serum tetracycline concentrations were decreased by 40% to 50% in 10 normal adults when coadministered with ferrous sulfate. The mechanism of this interaction is related to the formation of tetracycline-iron chelates in the GI tract that are poorly absorbed into circulation. Separating the doses of iron and the tetracycline by 2-4 hours appears to have a minimizing effect on the interaction. The AUC of several oral quinolone antibiotics is decreased when coadministered with oral iron preparations. The decreases may render the antibiotic ineffective. The mechanism of the interaction is presumed to be the formation of an insoluble complex between the antibiotic and the iron ion that is not readily absorbed in the GI tract.

6. Colestyramine + Digoxin

7. Colestyramine + Warfarin

8. Penicillamine + Metal-containing drugs

9. Sucralfate + Levothyroxine

10. Atropine + Antacids 11. Atropine + Amphetamine 12. Nicotine + Antacids 13. Cathartic + any drug

The AUC of digoxin was decreased by 32% in normal subjects when coadministered with cholestyramine. The mechanism of these interactions is likely related to the binding of the cardiac glycosides to the bile acid sequestrant in the GI tract, thus inhibiting absorption and interrupting enterohepatic circulation. The effect of colestipol appears minimal, and the effect of cholestyramine is variable. Concomitant administration of warfarin and cholestyramine decreased peak serum warfarin concentrations by more than 50% and decreased the prothrombin time by more than 25%. When the cholestyramine was administered 6 hours after the warfarin, the serum concentration and prothrombin time changes were reduced 16% and 0%, respectively. Similar results have been reported elsewhere. The mechanism of this interaction is possibly related to the ability of cholestyramine to bind warfarin in the GI tract both upon initial presentation and during the course of enterohepatic cycling. The absorption of penicillamine is reduced by iron (ferrous sulphate), magnesium and aluminum salts (for example, antacids) because they form unabsorbable complexes with penicillamine in the intestine. Administration of penicillamine and iron containing products or antacids should be separated by 2 hours. Concurrent sucralfate reduced serum T4 index by approximately 10% (p=0.038) and increased serum TSH by nearly 72%. Serum T3 index was not significantly different during sucralfate therapy. Some clinical studies conflict with other in vitro and in vivo studies suggesting that sucralfate binds to levothyroxine, preventing and/or delaying its absorption. Antacids, antidiarrheals: decreased atropine absorption Atropine and Amphetamine when in combination produces an antiinhibitory effect. Absorption of nicotine by ingestion is not complete because acid in the stomach prevents nicotine from being very well absorbed Digoxin absorption appeared to be the pharmacokinetic parameter most likely to be altered by fiber, any apparent effects tended to be small and seemed to reflect more of a delayed rather than diminished

14. Adsorbent + any drug

15. Antibiotic + Oral Contraceptive Drugs

16. Antibiotic + Digoxin

17. Warfarin + Phenylbutazone

18. Glibenclamide + Phenylbutazone

19. Oral Hypoglycemic + Aspirin

absorption. Activated charcoal absorbs substances in the stomach and intestines. Taking activated charcoal along with medications taken by mouth can decrease how much medicine your body absorbs, and decrease the effectiveness of your medication. To prevent this interaction, take activated charcoal at least one hour after medications you take by mouth. Individual patients do show large decreases in the plasma concentrations of ethinyl estradiol when they take certain other antibiotics, notably tetracycline and penicillin derivatives. Numerous antibiotic medications can increase digoxin levels, at times via potassium changes (with amphotericin B) or via increased absorption of digoxin. However, the most marked risk of digoxin toxicity occurs when digoxin is taken with macrolide antibiotics. Macrolides include erythromycin, clarithromycin and azithromycin. Both phenylbutazone and warfarin are extensively bound to plasma proteins, especially albumin, but phenylbutazone has a greater affinity for the binding sites. When the 2 drugs are taken concurrently, fewer binding sites are available for warfarin, thus increasing the amount of free anticoagulant and the risk of hemorrhage. Phenylbutazone also inhibits the metabolism of warfarin, resulting in continued enhancement of its anticoagulant effect. Since this agent is highly protein bound, the toxic potential is increased when given concomitantly with other highly protein bound drugs (ie, phenylbutazone, oral anticoagulants, hydantoins, salicylates, NSAIDs, beta-blockers, sulfonamides) - increase hypoglycemic effect. The product labeling for various hypoglycemic agents warn of increased risks of hypoglycemia with concurrent use of salicylates. Salicylates have been observed to enhance the blood glucose lowering effects of sulfonylureas. Hypoglycemic effects have been reported in both diabetic and nondiabetic patients receiving high dose salicylates. Salicylates may influence glucose regulation by several mechanisms including enhanced insulin secretion, reduced hepatic glucose output, and increased insulin sensitization.

20. Bilirubin + Aspirin

Drugs that can decrease Bilirubin levels are caffeine, penicillin, and high dose salicylates such as aspirin. The test helps determine if a patient has liver disease or a blocked bile duct.