Interaction between Alendronic acid and Mefenamic acid
Moderate Synergy

ID DDInter42 and DDInter1139
Interaction Theoretical concerns exist regarding the potential for increased risk and severity of gastrointestinal toxicity during coadministration of oral bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) due to additive or synergistic irritant effects on the gastrointestinal mucosa. Because NSAIDs reduce the rate of ulcer healing in the stomach and duodenum, it is also possible that NSAIDs may delay healing and exaggerate the mucosal injury caused by oral bisphosphonates. Theoretical concerns exist regarding the potential for increased risk and severity of renal impairment during coadministration of bisphosphonates with high dosages or chronic use of NSAIDs due to additive or synergistic nephrotoxic effects on the kidney. The use of bisphosphonates has been associated with nephrotoxicity manifested as deterioration of renal function and renal failure. Cases have primarily involved intravenous formulations of the drugs such as pamidronic acid and zoledronic acid, especially when they are administered too rapidly. The risk of hypocalcemia may also be increased, as drug-induced renal tubular damage can lead to renal loss of calcium and other electrolytes such as magnesium. Bisphosphonates alone often cause mild, asymptomatic hypocalcemia via inhibitive effects on bone resorption and possibly chelation of blood calcium. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with renal toxicities including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure.
Management Caution is advised if bisphosphonates are prescribed in combination with NSAIDs. Patients receiving oral bisphosphonates should be closely monitored for the development of gastrointestinal toxicity and advised to immediately report potential signs and symptoms such as severe abdominal pain, nausea, vomiting, diarrhea, loss of appetite, dizziness, lightheadedness, and/or black, tarry stools. Patients receiving intravenous formulations of bisphosphonates should have renal function and serum electrolytes closely monitored.
References
Alternative for Alendronic acid M05B
Burosumab
Denosumab
Cholecalciferol
Romosozumab
Alternative for Mefenamic acid M01A
Flurbiprofen (ophthalmic)
Chondroitin sulfate
Esomeprazole
Glucosamine
Suprofen (ophthalmic)
Diclofenac (ophthalmic)
Ketorolac (ophthalmic)
Diclofenac (topical)

Potential Metabolism Interactions

Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.