Table 3.
Details of the serious drug-drug interactions with steps taken by the treating physicians after reporting
| Offending drugs | Mechanism of serious DDI | Frequency | Steps taken by the treating physicians and explanations |
|---|---|---|---|
| Furosemide and amikacin | Each increases toxicity (ototoxicity and nephrotoxicity) of the other by pharmacodynamic synergism | 5 | Furosemide was stopped in 3 patients with chronic kidney disease and sepsis In 2 patients with pulmonary edema and sepsis, no modification of prescription was done, without further decline in renal function Ototoxicity was not evaluated |
| Rifampin and dexamethasone | Rifampin decreases the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism | 3 | No modification of prescription was done Dexamethasone was continued as all were cases of tubercular meningitis |
| Enoxaparin and warfarin | Both increase anticoagulation | 2 | No modification of prescription was done as both were cases of peripheral venous thrombosis requiring anticoagulant therapyINR was monitored routinely |
| Omeprazole and digoxin | Omeprazole increases the level or effect of digoxin by increasing gastric pH | 1 | Omeprazole and digoxin were dosed 12 h apart |
| Omeprazole and clopidogrel | Omeprazole decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism | 1 | Omeprazole was stopped |
| Tramadol and codeine | Both may reinitiate opiate dependence in patients previously addicted to other opiates and may also provoke withdrawal in opiate-dependent patients | 1 | Codeine-containing cough syrup was stopped |
| Azithromycin and digoxin | Azithromycin increases the level or effect of digoxin by altering intestinal flora | 1 | No modification of prescription was done Azithromycin was stopped after 3 days |
| Artesunate and ondansetron | Both increase QTc interval | 1 | No modification of prescription was done Periodic ECG showed no abnormality |
| Rifampin and hydrocortisone | Rifampin decreases the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism | 1 | No modification of prescription was done Hydrocortisone was continued as it was a case of tubercular meningitis |
| Heparin and warfarin | Both increase anticoagulation | 1 | No modification of prescription was done in this patient with cerebrovascular accidentINR was monitored routinely |
| Aspirin and enalapril | Both cause pharmacodynamic antagonism which can result in a significant decrease in renal function. Aspirin reduces the synthesis of vasodilating renal prostaglandins and thus diminishes the antihypertensive effect of enalapril | 1 | No modification of prescription was done Both the drugs were indicated in this case of coronary arterial disease with hypertension |
| Piperacillin and heparin | Piperacillin increases the level or effect of heparin by anticoagulation; piperacillin can inhibit platelet aggregation | 1 | No modification of prescription was done Both the drugs were indicated in this case of ventilator-associated pneumonia with venous thrombosis |
| Carbamazepine and dexamethasone | Carbamazepine decreases the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism | 1 | No modification of prescription was done |
| Carbamazepine and atorvastatin | Carbamazepine decreases the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism | 1 | No modification of prescription was done |
| Ceftriaxone and calcium gluconate | Both increase the risk of potentially fatal particulate precipitation in lungs and kidneys | 1 | No modification of prescription was done |
| Calcium gluconate and doxycycline | Both decrease levels of the other by inhibition of GI absorption | 1 | No modification of prescription was done |
| Ritonavir and atorvastatin | Ritonavir increases toxicity of atorvastatin, OATP1B1 inhibitors may increase risk of myopathy | 1 | No modification of prescription was done |
CYP=Cytochrome P450 enzyme, DDIs=Drug-drug interactions, ECG=Electrocardiogram, INR=International normalized ratio, OATP=Organic anion-transporting polypeptide, GI=Gastrointestinal