Department of Pharmacology, GRT Institute of Pharmaceutical Education and Research, Thirutani.
Background Drug-drug interactions result in unintended reactions, toxic side effects, or a lack of clinical efficacy in an individual body when multiple medications are simultaneously administered for one or more disease. Pharmacokinetic interactions concerning drug absorption, distribution, metabolism, and excretion (ADME cycle) variations may result in a plasma concentration fluctuation, influencing drug bioavailability. Pharmacodynamically, drugs can interact by binding to the same receptor. Aim and Objective Our study focuses on exploring the interaction profile of Gastric irritant drugs (NSAIDs, Iron supplements and Antibiotics) and drugs used in the treatment of Gastric irritation using online software (drugs.com). Result and Discussion Usually NSAIDs, Iron supplements and Antibiotics are concomitantly given with gastric acid suppressants (Antacids, Proton pump inhibitors, H2 blockers, Prokinetic agents) to tackle their gastric side effects. This study aided to determine the combinations of Iron supplements and Antibiotics and gastric acid suppressants that are free from drug interactions. Conclusion This would serve as a ready reference guide for medical practitioners, pharmacists and other health care professionals to choose combination of NSAIDs, Iron supplements and Antibiotics and gastric acid suppressants to treat or prevent their gastric side effects in a more efficient manner
In pharmacology, drug-drug interactions result in unintended reactions, toxic side effects, or a lack of clinical efficacy in an individual body when multiple medications are simultaneously administered for one or more disease [46]. These are usually considered in terms of two principal classes of underlying mechanisms: pharmacodynamics and pharmacokinetics [47]. Indeed, the pharmacological effect of one or both drugs may be enhanced or suppressed, or a new and unanticipated adverse effect may occur, even leading to fatal consequences; Concerning pharmacokinetics, drug absorption, distribution, metabolism, and excretion (ADME cycle) variations may result in a plasma concentration fluctuation, influencing drug bioavailability. Interactions between drugs at the metabolic level can modify the metabolic enzymes altering drug activation or inactivation. If the metabolism is inhibited, it will remain longer in the body, so its concentration will increase, potentially causing secondary toxic effects. Conversely, metabolism enhancement can decrease plasma concentration and hence its bioavailability [48]. Pharmacodynamically, drugs can interact by binding to the same receptor. Two receptor agonists or two antagonists would increase the pharmacological actions of both, whereas an agonist and an antagonist would decrease each other’s pharmacological effects. In some interactions, drugs may produce biochemical changes that alter the sensitivity to toxicities produced by other drugs. Finally, whereas in the majority of cases, drug-drug interactions can cause toxic adverse effects (e.g., beta-blockers and bronchodilators; diuretics and steroids or digoxin; rifampicin and verapamil or carbamazepine), there are also several therapeutically beneficial drug interactions (e.g., docetaxel and piperine; resveratrol and diclofenac; ivermectin and lopinavir or saquinavir) [49].
Our study focuses on exploring the interaction profile of Gastric irritant drugs (NSAIDs, Iron supplements and Antibiotics) and drugs used in the treatment of Gastric irritation using online software (drugs.com).
Many drugs can cause gastric irritation, including [44]:
Some common medications used to treat gastrointestinal (GI) side effects include [45]:
These are available in liquid and pill forms and can treat heartburn, sour stomach, and acid indigestion. Common antacids include:
These can reduce stomach acid production and help heal inflammation and ulcers in the GI tract. Examples include omeprazole, lansoprazole, and pantoprazole
These can help with heartburn and sour stomach, and can also reduce pain from ulcers. Examples include cimetidine, ranitidine hydrochloride, and famotidine
These include metoclopramide
Interactions of Gastric irritant drugs (NSAIDs, Iron supplements and Antibiotics) and drugs used in the treatment of Gastric irritation (Table 1)
Interaction between Aspirin (Salicylates) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
Interaction type: Moderate
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 [1, 2, 3].
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 [1, 2, 3].
Interactions between Aspirin (Salicylates) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
Interaction type: Minor
Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats [4,5,6]. Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates [4,5,6].
Interactions between Aspirin (Salicylates) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
No drug interactions were found.
Interactions between Aspirin (Salicylates) and Metoclopramide (Promotility agents)
Interaction type: Minor
Coadministration with metoclopramide may enhance the rate and extent of absorption of drugs that are mainly absorbed in the small intestine, such as paracetamol, aspirin, and tetracycline. The proposed mechanism is a metoclopramide-mediated increase in gastric emptying. Clinical and laboratory monitoring should be considered and the dose adjusted as appropriate. The clinical significance of this interaction is unknown [7,8,9].
Interactions between Ibuprofen (NSAIDs) and Aluminum Hydroxide, Calcium Carbonate (Antacids)
No drug interactions were found.
Interactions between Ibuprofen (NSAIDs) and Magnesium Hydroxide (Antacids)
Interaction type: Minor
One study has suggested that coadministration of magnesium hydroxide and ibuprofen may significantly increase the area under the plasma concentration-time curve for ibuprofen. This increase may be clinically beneficial in circumstances in which a rapid response to ibuprofen is desirable [10].
Interactions between Ibuprofen (NSAIDs) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
No drug interactions were found.
Interactions between Ibuprofen (NSAIDs) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
Interaction type: Minor
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data are varied, even for the same NSAID. The mechanism may be related to inhibition of metabolism, changes in gastric pH that decrease absorption, and/or reduced urinary elimination. Statistically significant changes have been small and of limited clinical significance. Clinical monitoring of patient response and tolerance is recommended [11, 12, 13].
Interactions between Ibuprofen (NSAIDs) and Metoclopramide (Promotility agents)
No drug interactions were found.
Interactions between Naproxen (NSAIDs) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
Interaction type: Minor
Antacids and some oral aluminum, calcium, or magnesium containing preparations may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) produced by antacids. In patients treated with antacids, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered. Concomitant use of these drugs is generally not recommended. Aluminum hydroxide and some magnesium-containing antacids have also been reported to reduce the absorption of regular naproxen. The interaction may be minimized by separating the times of administration by at least 2 hours [14,15].
Interactions between Naproxen (NSAIDs) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
Interaction type: Minor
Monitor: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered [16].
Management: Concomitant use of these drugs is generally not recommended [16].
Interactions between Naproxen (NSAIDs) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
Interaction type: Minor
Monitor: The concomitant administration of H2 blockers may increase the dissolution rate of enteric-coated naproxen, causing the drug to be released in the stomach instead of the small intestine[16].
Management: H2 antagonists should be avoided in patients taking enteric-coated formulations of naproxen [16].
Interactions between Naproxen (NSAIDs) and Metoclopramide (Promotility agents)
No drug interactions were found.
Interactions between Ketoprofen (NSAIDs) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
No drug interactions were found.
Interactions between Ketoprofen (NSAIDs) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
No drug interactions were found.
Interactions between Ketoprofen (NSAIDs) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
Interaction type: Minor
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data are varied, even for the same NSAID. The mechanism may be related to inhibition of metabolism, changes in gastric pH that decrease absorption, and/or reduced urinary elimination. Statistically significant changes have been small and of limited clinical significance. Clinical monitoring of patient response and tolerance is recommended [11,12,13].
Interactions between Ketoprofen (NSAIDs) and Metoclopramide (Promotility agents)
No drug interactions were found.
Interactions between Etodolac (NSAIDs) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
No drug interactions were found.
Interactions between Etodolac (NSAIDs) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
No drug interactions were found.
Interactions between Etodolac (NSAIDs) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
Interaction type: Minor
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data are varied, even for the same NSAID. The mechanism may be related to inhibition of metabolism, changes in gastric pH that decrease absorption, and/or reduced urinary elimination. Statistically significant changes have been small and of limited clinical significance. Clinical monitoring of patient response and tolerance is recommended [11,12,13].
Interactions between Etodolac (NSAIDs) and Metoclopramide (Promotility agents)
No drug interactions were found.
Interactions between Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
Interaction type: Moderate
Adjust Dosing Interval: The bioavailability of orally administered iron may be reduced by concomitant administration of antacids or other agents with acid-neutralizing effects. The exact mechanism is unknown but may involve reduced iron solubility due to increase in gastric pH and/or reduced absorption due to complexation or precipitation of the iron. Based on existing data, sodium bicarbonate and calcium carbonate appear to have greater effects than antacids containing magnesium and aluminum hydroxides. In a study of patients with mild iron deficiency anemia, coadministration of ferrous sulfate with sodium bicarbonate 1 gram and calcium carbonate 500 mg reduced iron absorption by 50% and 67%, respectively, while 5 mL of an antacid containing magnesium and aluminum hydroxides had little effect. Another study also found no effect on iron absorption when ferrous sulfate (equivalent to 10 mg/kg of elemental iron) was coadministered with magnesium hydroxide (1 mg for every 5 mg of elemental iron ingested) in a group of healthy, fasting male subjects. In contrast, absorption of iron from ferrous sulfate and ferrous fumarate tablets was reduced by 37% and 31%, respectively, following administration of an antacid containing magnesium carbonate, magnesium hydroxide, and aluminum hydroxide in a study of healthy, iron-replete volunteers. Similarly, in a study of nine patients, coadministration of 5 mg of ferrous sulfate with a 35 gram dose of magnesium trisilicate was found to reduce iron absorption by an average of more than 70%. The interaction reportedly does not occur in the presence of ascorbic acid, which may competitively bind with iron and prevent the interference with iron absorption [17,18,19].
Management: To minimize the potential for interaction, it may be appropriate to administer oral iron preparations at least two hours apart from antacids or other agents with acid-neutralizing effects [17,18,19].
Interactions between Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) and Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
Interaction type: Moderate
Monitor: Inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may impair the gastrointestinal absorption of nonheme iron, a process that is dependent on an acidic environment. The interaction was suspected in two patients with iron deficiency anemia due to gastrointestinal blood loss that were unresponsive to oral iron replacement therapy, even after the bleeding had apparently stopped. Both patients had been on omeprazole for six months while being treated with ferrous sulfate. An iron-loading test was performed on one of the patients and indicated iron malabsorption. Within two months after discontinuation of omeprazole, notable improvements in hemoglobin level and mean corpuscular volume (MCV) were observed in both patients, and iron absorption was significantly increased in the patient who underwent absorption testing. In a case review of patients with hereditary hemochromatosis treated at one institution, investigators observed a reduced requirement for maintenance phlebotomy in seven patients following initiation of PPI therapy (mean 2.5 L blood removed/year before PPI therapy vs. 0.5 L/year during PPI therapy), presumably due to reduced tissue iron accumulation stemming from impaired absorption of dietary nonheme iron. Mean annual phlebotomy requirement during PPI therapy in these patients was also lower than that in controls who had never taken a PPI (mean 2.3 L blood removed/year). The same group of investigators also studied iron absorption in 14 patients fed an iron-loaded meal before and after PPI therapy for one week. PPI therapy was associated with a 51% reduction in area under the serum iron concentration-time curve (AUC 0 to 4 hours); a 55% reduction in maximum increase of serum iron following ingestion of iron-loaded meal; and a 46% reduction in percent recovery of administered iron at peak serum iron concentration. Interestingly, the interaction has not been reported in healthy, iron-replete individuals. In a study of 109 patients with Zollinger-Ellison syndrome who had not undergone gastric resection, omeprazole treatment for an average of 5.7 years did not significantly decrease body iron stores or cause iron deficiency compared to H2-receptor antagonist therapy or no gastric acid-suppressant treatment. It is possible that the interaction may not affect people with healthy iron stores because of compensation by dietary heme iron, which typically comprises only a small fraction of dietary iron but whose absorption is not dependent on gastrointestinal pH. In contrast, dietary heme iron alone may not be sufficient to restore normal iron balance in patients with anemia or those with defective regulatory mechanisms of iron absorption[20,21,22].
Management: Patients with iron deficiency may not respond adequately to oral iron replacement therapy during coadministration of PPIs or PCABs. If an interaction is suspected after ruling out other causes, it may be appropriate to discontinue the PPI or PCAB or consider administering iron parenterally[20,21,22].
Interactions between Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) and Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
Interaction type: Minor
Limited data have suggested that concurrent administration of cimetidine may reduce the bioavailability of orally administered iron. In one study, dose-related reductions in the absorption of iron occurred following single oral doses of cimetidine (300 mg to 900 mg) compared to baseline. There has also been a case report of persistent inadequate response to iron therapy for the treatment of anemia during concomitant use of cimetidine 1 gm and ferrous sulfate 600 mg daily. Hematologic improvement was noted within a month after reducing the cimetidine dosage to 400 mg daily. Some investigators have suggested that cimetidine-induced increases in gastric pH may reduce the solubility of iron salts, which leads to decreased absorption. However, a study in patients with iron deficiency or iron-deficiency anemia found that response to iron therapy (iron succinyl-protein complex 2400 mg twice daily) was not affected by H2-receptor antagonists such as famotidine, nizatidine, or ranitidine. In another study, stable serum iron concentrations were observed in 64 patients receiving chronic therapy with cimetidine 400 mg to 800 mg/day. Based on existing evidence, no intervention (e.g., separating times of administration) appears to be necessary during concomitant use of cimetidine and iron products unless an interaction is suspected [23,24,25].
Interactions between Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) and Metoclopramide (Promotility agents)
No drug interactions were found.
Interactions between Clarithromycin (Macrolides) and Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids)
No drug interactions were found.
Interactions between Clarithromycin (Macrolides) and Omeprazole (Proton Pump Inhibitors)
Interaction type: Minor
Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH [26,27,28].
Interactions between Clarithromycin (Macrolides) and Lansoprazole (Proton Pump Inhibitors)
Interaction type: Moderate
Monitor: Coadministration with clarithromycin may increase the plasma concentrations of lansoprazole. The proposed mechanism is clarithromycin inhibition of intestinal (first-pass) and hepatic metabolism of lansoprazole via CYP450 3A4. Although lansoprazole is primarily metabolized by CYP450 2C19 in the liver, 3A4-mediated metabolism is the predominant pathway in individuals who are 2C19-deficient (approximately 3% to 5% of the Caucasian and 17% to 20% of the Asian population). Additionally, inhibition of P-glycoprotein intestinal efflux transporter by clarithromycin may also contribute to the interaction, resulting in increased bioavailability of lansoprazole. In 18 healthy volunteers--six each of homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs) of CYP450 2C19--clarithromycin (400 mg orally twice a day for 6 days) increased the peak plasma concentration (Cmax) of a single 60 mg oral dose of lansoprazole by 1.47, 1.71- and 1.52-fold, respectively, and area under the concentration-time curve (AUC) by 1.55-, 1.74- and 1.80-fold, respectively, in each of these groups compared to placebo. The AUC ratio of lansoprazole-to-lansoprazole sulphone, which is considered an index of CYP450 3A4 activity, was significantly increased by clarithromycin in all three groups. However, elimination half-life of lansoprazole was prolonged by 1.54-fold only in PMs. Mild diarrhea was reported in two subjects and mild abdominal disturbance in six subjects during clarithromycin coadministration. These side effects continued until day 6 and ameliorated the day after discontinuation of clarithromycin, whereas no adverse events were reported during placebo administration or after lansoprazole plus placebo. In another study, clarithromycin induced dose-dependent increases in the plasma concentration of lansoprazole in a group of 20 patients receiving treatment for H. pylori eradication. Mean 3-hour plasma lansoprazole concentration was 385 ng/mL for the control subjects who received lansoprazole 30 mg and amoxicillin 750 mg twice a day for 7 days; 696 ng/mL for patients coadministered clarithromycin 200 mg twice a day; and 947 ng/mL for patients coadministered clarithromycin 400 mg twice a day [29,30,31].
Management: Although lansoprazole is generally well tolerated, caution may be advised during coadministration with clarithromycin, particularly if higher dosages of one or both drugs are used. Dosage adjustment may be necessary in patients who experience excessive adverse effects of lansoprazole [29,30,31].
Interactions between Clarithromycin (Macrolides) and Pantoprazole (Proton Pump Inhibitors)
No drug interactions were found.
Interactions between Clarithromycin (Macrolides) and Cimetidine (H2 (Histamine)) blockers
Interaction type: Minor
Coadministration of cimetidine (800 mg dosed to steady state) and clarithromycin (500 mg as a single dose) prolonged the absorption of clarithromycin resulting in decreased peak plasma concentration of clarithromycin and its metabolite and significantly increased half-lives. There were no changes in clearance or AUC. The mechanism and clinical significance of this interaction are unknown. Patients receiving this combination should be monitored for possible subtherapeutic effects of the antibiotic [32].
Interactions between Clarithromycin (Macrolides) and Ranitidine (H2 (Histamine)) blockers
No drug interactions were found.
Interactions between Clarithromycin (Macrolides) and Famotidine (H2 (Histamine)) blockers
Interaction type: Moderate
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) [33,34,35].
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 [33,34,35].
Interactions between Clarithromycin (Macrolides) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Cefdinir (Cephalosporins) and Aluminum hydroxide, Magnesium hydroxide (Antacids)
Interaction type: Moderate
Adjust Dosing Interval: Aluminum- or magnesium-containing antacids may interfere with the rate and extent of absorption of cefdinir. The mechanism has not been described but is most likely due to a chelation effect by the antacid or a change in intragastric pH [36].
Management: If an antacid must be administered during cefdinir therapy, separate the times of administration by at least two hours [36].
Interactions between Cefdinir (Cephalosporins) and Calcium Carbonate (Antacids)
No drug interactions were found.
Interactions between Cefdinir (Cephalosporins) and Omeprazole, Lansoprazole, and Pantoprazole (Proton pump inhibitors)
No drug interactions were found.
Interactions between Cefdinir (Cephalosporins) and Cimetidine, Ranitidine hydrochloride, and Famotidine (H2 (Histamine) blockers)
No drug interactions were found.
Interactions between Cefdinir (Cephalosporins) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Cefpodoxime (Cephalosporins) and Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids); Proton pump inhibitors (Omeprazole, Lansoprazole, and Pantoprazole); H2 (Histamine) blockers (Cimetidine, Ranitidine Hydrochloride, and Famotidine)
Interaction type: Moderate
Generally, Avoid: The coadministration with H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH may reduce the oral bioavailability of cefpodoxime proxetil and cefuroxime axetil. The proposed mechanism is a pH-dependent reduction in drug dissolution and absorption. In ten healthy volunteers, famotidine 40 mg administered one hour before the ingestion of cefpodoxime proxetil 200 mg led to an approximately 40% reduction in the cefpodoxime peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) compared to when the drug was given alone. Similar results were reported with ranitidine in another study, where cefpodoxime Cmax and AUC decreased by approximately 30%. Likewise, pretreatment with ranitidine plus sodium bicarbonate decreased the Cmax and AUC of cefuroxime by over 40% in six healthy volunteers. The clinical significance of these effects is unknown, but potentially reduced antibiotic efficacy should be considered[37,38,39].
Management: Until further data are available, patients treated with cefpodoxime proxetil or cefuroxime axetil may want to avoid using H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH. An alternative antibiotic may be considered if these medications cannot be discontinued[37,38,39].
Interactions between Cefpodoxime (Cephalosporins) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Ciprofloxacin, Levofloxacin (Fluoroquinolones) and Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids)
Interaction type: Moderate
Adjust Dosing Interval: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide [40,41,42].
Management: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations[40,41,42].
Interactions between Ciprofloxacin (Fluoroquinolones) and Omeprazole (Proton pump inhibitors)
Interaction type: Minor
According to the product labeling, absorption of the extended-release formulation of ciprofloxacin was slightly diminished (20%) when given concomitantly with omeprazole. The mechanism and clinical significance of this interaction are unknown [43].
Interactions between Ciprofloxacin (Fluoroquinolones) and Lansoprazole, Pantoprazole (Proton pump inhibitors)
No drug interactions were found.
Interactions between Ciprofloxacin (Fluoroquinolones) and Cimetidine, Ranitidine Hydrochloride (H2 (Histamine) blockers)
No drug interactions were found.
Interactions between Ciprofloxacin (Fluoroquinolones) and Famotidine (H2 (Histamine) blockers)
Interaction type: Moderate
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) [33].
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 [33].
Interactions between Ciprofloxacin (Fluoroquinolones) and Metoclopramide Metoclopramide (Prokinetic agents)
Interaction type: Minor
Metoclopramide increases the rate of absorption of oral ciprofloxacin, resulting in a shorter time to reach maximum plasma concentrations. The bioavailability is not affected. The probable mechanism is increased gastric motility by metoclopramide. The clinical significance are unknown [43].
Interactions between Levofloxacin (Fluoroquinolones) and Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids)
No drug interactions were found.
Interactions between Levofloxacin (Fluoroquinolones) and Omeprazole, Lansoprazole, Pantoprazole (Proton pump inhibitors)
No drug interactions were found.
Interactions between Levofloxacin (Fluoroquinolones) and Cimetidine, Ranitidine Hydrochloride, Famotidine (H2 (Histamine) blockers)
No drug interactions were found.
Interactions between Levofloxacin (Fluoroquinolones) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Levofloxacin (Fluoroquinolones) and Cimetidine, Ranitidine Hydrochloride, Famotidine (H2 (Histamine) blockers)
No drug interactions were found.
Interactions between Levofloxacin (Fluoroquinolones) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Amoxicillin (Penicillins) and Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids); Proton pump inhibitors (Omeprazole, Lansoprazole, and Pantoprazole); H2 (Histamine) blockers (Cimetidine, Ranitidine Hydrochloride, and Famotidine) Metoclopramide (Prokinetic agents)
No drug interactions were found.
Interactions between Ampicillin (Penicillins) and Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids)
No drug interactions were found.
Interactions between Ampicillin (Penicillins) and Proton pump inhibitors (Omeprazole, and Pantoprazole)
No drug interactions were found.
Interactions between Ampicillin (Penicillins) and Lansoprazole (Proton pump inhibitors)
Interaction type: Moderate
Generally, Avoid: Because lansoprazole increases gastric pH, it theoretically could decrease absorption of drugs like ampicillin which require an acidic environment[21].
Management: If lansoprazole therapy is required, consideration should be given to alternative antimicrobial agents[21].
Interactions between Ampicillin (Penicillins) and Cimetidine, Ranitidine Hydrochloride, and Famotidine (H2 (Histamine) blockers)
No drug interactions were found.
Interactions between Ampicillin (Penicillins) and Metoclopramide (Prokinetic agents)
No drug interactions were found.
Table 1: Drug Interaction table: Study of Gastric irritant drugs (NSAIDs, Iron supplements and Antibiotics) and drugs used in the treatment of Gastric irritation
|
S. No |
Gastric irritant drugs |
Drugs used in the treatment of Gastric irritation |
Interaction type |
Details |
|
1. |
Aspirin (Salicylates)
|
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Moderate |
Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. 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 [1, 2, 3]. |
|
2. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Minor |
Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates [4,5,6]. |
|
|
3. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers |
Not applicable |
No drug interactions were found. |
|
|
4. |
Metoclopramide (Promotility agents) |
Minor |
Coadministration with metoclopramide may enhance the rate and extent of absorption of drugs that are mainly absorbed in the small intestine, such as paracetamol, aspirin, and tetracycline [7,8,9]. |
|
|
5. |
Ibuprofen (NSAIDs) |
Aluminium Hydroxide, Calcium Carbonate (Antacids) |
Not applicable |
No drug interactions were found. |
|
6. |
Magnesium Hydroxide (Antacids) |
Minor |
One study has suggested that coadministration of magnesium hydroxide and ibuprofen may significantly increase the area under the plasma concentration-time curve for ibuprofen [10]. |
|
|
7. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers |
Minor |
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data are varied, even for the same NSAID [11, 12, 13]. |
|
|
8. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
9. |
Naproxen (NSAIDs) |
Aluminium Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Minor |
Antacids and some oral aluminum, calcium, or magnesium containing preparations may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution [14,15]. |
|
10. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors)
|
Minor |
In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered [16]. Management: Concomitant use of these drugs is generally not recommended [16]. |
|
|
11. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
|
Minor |
The concomitant administration of H2 blockers may increase the dissolution rate of enteric-coated naproxen, causing the drug to be released in the stomach instead of the small intestine [16]. |
|
|
12. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
13. |
Ketoprofen (NSAIDs) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
14. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
15. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers |
Minor |
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations [11,12,13]. |
|
|
16. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
17. |
Etodolac (NSAIDs)
|
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
18. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
19. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
|
Minor |
H2 antagonists may alter the disposition of nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data are varied, even for the same NSAID [11,12,13]. |
|
|
20. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
21. |
Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Moderate |
The bioavailability of orally administered iron may be reduced by concomitant administration of antacids or other agents with acid-neutralizing effects [17,18,19]. |
|
22. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Moderate |
Inhibitors of the proton pump (PPIs or potassium-competitive acid blockers [PCABs]) may impair the gastrointestinal absorption of nonheme iron, a process that is dependent on an acidic environment [20,21,22] . Management: Patients with iron deficiency may not respond adequately to oral iron replacement therapy during coadministration of PPIs or PCABs. If an interaction is suspected after ruling out other causes, it may be appropriate to discontinue the PPI or PCAB or consider administering iron parenterally [20,21,22]. |
|
|
23. |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers
|
Minor |
Limited data have suggested that concurrent administration of cimetidine may reduce the bioavailability of orally administered iron[23,24,25]. |
|
|
24. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
25. |
Clarithromycin (Macrolides) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
26. |
Omeprazole (Proton Pump Inhibitors) |
Minor |
Clarithromycin may increase and prolong the omeprazole plasma concentration [26,27,28]. |
|
|
27. |
Lansoprazole (Proton Pump Inhibitors) |
Moderate |
Coadministration with clarithromycin may increase the plasma concentrations of lansoprazole [29,30,31]. Management: Although lansoprazole is generally well tolerated, caution may be advised during coadministration with clarithromycin, particularly if higher dosages of one or both drugs are used. Dosage adjustment may be necessary in patients who experience excessive adverse effects of lansoprazole [29,30,31].
|
|
|
28. |
Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
29. |
Cimetidine (H2 (Histamine)) blockers |
Minor |
Coadministration of cimetidine (800 mg dosed to steady state) and clarithromycin (500 mg as a single dose) prolonged the absorption of clarithromycin resulting in decreased peak plasma concentration of clarithromycin and its metabolite and significantly increased half-lives [32]. |
|
|
30. |
Ranitidine (H2 (Histamine)) blockers |
Not applicable |
No drug interactions were found. |
|
|
31. |
Famotidine (H2 (Histamine)) blockers |
Moderate |
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 [33,34,35]. 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 [33,34,35]. |
|
|
32. |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
33. |
Cefdinir (Cephalosporins) |
Aluminum hydroxide, Magnesium hydroxide (Antacids)
|
Moderate |
Adjust Dosing Interval: Aluminum- or magnesium-containing antacids may interfere with the rate and extent of absorption of cefdinir. The mechanism has not been described but is most likely due to a chelation effect by the antacid or a change in intragastric pH [36]. |
|
34. |
Calcium Carbonate (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
35. |
Omeprazole, Lansoprazole, and Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
36. |
Cimetidine, Ranitidine hydrochloride, and Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
37. |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
38. |
Cefpodoxime (Cephalosporins) |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids); Proton pump inhibitors (Omeprazole, Lansoprazole, and Pantoprazole); H2 (Histamine) blockers (Cimetidine, Ranitidine Hydrochloride, and Famotidine)
|
Moderate |
Generally, Avoid: The coadministration with H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH may reduce the oral bioavailability of cefpodoxime proxetil and cefuroxime axetil [37,38,39]. Management: Until further data are available, patients treated with cefpodoxime proxetil or cefuroxime axetil may want to avoid using H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH. An alternative antibiotic may be considered if these medications cannot be discontinued[37,38,39]. |
|
39. |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
40. |
Ciprofloxacin, Levofloxacin (Fluoroquinolones) |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids) |
Moderate |
Adjust Dosing Interval: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics[40,41,42] Management: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations[40,41,42]. |
|
41. |
Ciprofloxacin (Fluoroquinolones) |
Omeprazole (Proton pump inhibitors) |
Minor |
According to the product labeling, absorption of the extended-release formulation of ciprofloxacin was slightly diminished (20%) when given concomitantly with omeprazole [43]. |
|
42. |
Lansoprazole, Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
43. |
Cimetidine, Ranitidine Hydrochloride (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
44. |
Famotidine (H2 (Histamine) blockers) |
Moderate |
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 [33]. 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 [33]. |
|
|
45. |
Metoclopramide Metoclopramide (Prokinetic agents) |
Minor |
Metoclopramide increases the rate of absorption of oral ciprofloxacin, resulting in a shorter time to reach maximum plasma concentrations[43]. |
|
|
46. |
Levofloxacin (Fluoroquinolones) |
Cimetidine, Ranitidine Hydrochloride, Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
47. |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
48. |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
49. |
Omeprazole, Lansoprazole, Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
50. |
Amoxicillin (Penicillins) |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids); Proton pump inhibitors (Omeprazole, Lansoprazole, and Pantoprazole); H2 (Histamine) blockers (Cimetidine, Ranitidine Hydrochloride, and Famotidine) Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
51. |
Ampicillin (Penicillins) |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
52. |
Proton pump inhibitors (Omeprazole, and Pantoprazole) |
Not applicable |
No drug interactions were found. |
|
|
53. |
Lansoprazole (Proton pump inhibitors) |
Moderate |
Generally, Avoid: Because lansoprazole increases gastric pH, it theoretically could decrease absorption of drugs like ampicillin which require an acidic environment[21]. |
|
|
54. |
Cimetidine, Ranitidine Hydrochloride, and Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
55. |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
RESULTS AND DISCUSSION
Usually NSAIDs, Iron supplements and Antibiotics are concomitantly given with gastric acid suppressants (Antacids, Proton pump inhibitors, H2 blockers, Prokinetic agents) to tackle their gastric side effects.
Our study helped to find out the drug interactions from the above-mentioned combination of drugs (Table 2).
Here we list the combination of the drugs without any interactions.
Table 2: List of NSAIDs, Iron supplements and Antibiotics and gastric acid suppressants combinations without drug interactions
|
S. No |
Gastric irritant drugs |
Drugs used in the treatment of Gastric irritation |
Interaction type |
Details |
|
1. |
Aspirin (Salicylates) |
Cimetidine, Ranitidine, and Famotidine (H2 (Histamine)) blockers |
Not applicable |
No drug interactions were found. |
|
2. |
Ibuprofen (NSAIDs) |
Aluminum Hydroxide, Calcium Carbonate (Antacids) |
Not applicable |
No drug interactions were found. |
|
3. |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
4. |
Naproxen (NSAIDs) |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
5. |
Ketoprofen (NSAIDs) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
|
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
|
6. |
Etodolac (NSAIDs) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
Omeprazole, Lansoprazole, and Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
7. |
Ferrous Sulfate, Ferrous Gluconate, Ferrous Fumarate (Iron supplements) |
Metoclopramide (Promotility agents) |
Not applicable |
No drug interactions were found. |
|
8. |
Clarithromycin (Macrolides) |
Aluminum Hydroxide, Calcium Carbonate, Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
Pantoprazole (Proton Pump Inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
|
Ranitidine (H2 (Histamine)) blockers |
Not applicable |
No drug interactions were found. |
|
|
|
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
9. |
Cefdinir (Cephalosporins) |
Calcium Carbonate (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
Omeprazole, Lansoprazole, and Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
|
Cimetidine, Ranitidine hydrochloride, and Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
|
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
10. |
Cefpodoxime (Cephalosporins) |
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
11. |
Ciprofloxacin (Fluoroquinolones) |
Lansoprazole, Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
Cimetidine, Ranitidine Hydrochloride (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
12. |
Levofloxacin (Fluoroquinolones) |
Cimetidine, Ranitidine Hydrochloride, Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
|
|
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids) |
Not applicable |
No drug interactions were found. |
|
|
|
Omeprazole, Lansoprazole, Pantoprazole (Proton pump inhibitors) |
Not applicable |
No drug interactions were found. |
|
|
13. |
Amoxicillin (Penicillins) |
Aluminum Hydroxide, Calcium Carbonate and Magnesium Hydroxide (Antacids); Proton pump inhibitors (Omeprazole, Lansoprazole, and Pantoprazole); H2 (Histamine) blockers (Cimetidine, Ranitidine Hydrochloride, and Famotidine) Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
|
14. |
Ampicillin (Penicillins) |
Cimetidine, Ranitidine Hydrochloride, and Famotidine (H2 (Histamine) blockers) |
Not applicable |
No drug interactions were found. |
|
|
Metoclopramide (Prokinetic agents) |
Not applicable |
No drug interactions were found. |
Limitations of the study
The drugs in this study were analysed and recommendations of the combinations of NSAIDs, Iron supplements and Antibiotics with gastric acid suppressants are only based on the interaction data but not based on the type and severity of the gastrointestinal side effects.
CONCLUSION
This would serve as a ready reference guide for medical practitioners, pharmacists and other health care professionals to choose combination of NSAIDs, Iron supplements and Antibiotics and gastric acid suppressants to treat or prevent their gastric side effects in a more efficient manner.
The study can be extended by analysing mechanisms of the drug interaction.
REFERENCES
Deepak Venkataraman N.*, Sriraj S., Purushothaman K., Muasolivendhan M., Charumathi P., Bharathwaj J., Lakshminarasimman S., Sudharsan S., Drug Interaction Study of Gastric Irritant Drugs (Nsaids, Iron Supplements and Antibiotics) And Drugs Used in The Treatment of Gastric Irritation Using Online Software, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 1219-1242. https://doi.org/10.5281/zenodo.14363551
10.5281/zenodo.14363551
