Drug-drug combination | Effect |
ACE inhibitors + potassium supplements | Hyperkalemia |
ACE inhibitors + spironolactone | Hyperkalemia |
Digoxin + amiodarone | Digoxin toxicity |
Digoxin + verapamil | Bradycardia, heart block, digoxin toxicity |
Theophylline + quinolones | Theophylline toxicity, seizures |
Warfarin + macrolides/quinolones/sulfa antibiotics | Bleeding |
Warfarin + NSAIDs | Gastrointestinal bleeding |
Warfarin + phenytoin | Warfarin toxicity, phenytoin toxicity |
Simvastatin + fluconazole | Increased simvastatin levels, liver toxicity |
Levothyroxine + omeprazole | Decreased absorption of levothyroxine |
Metronidazole + alcohol | Nausea, vomiting, flushing, headache |
A specific situation where a medicine, procedure, or surgery should not be used because it may harm the person. Drugs may be contraindicated due to underlying disease, such as liver or kidney failure, underlying conditions, like pregnancy or old age, or severe interactions with other medications.
There are two types of contraindications:
Relative contraindication: This means that there is a severe risk of harm if the medication(s) is used. However, it can be beneficial in specific circumstances and can be used with risk-minimizing actions like increased monitoring for drug levels or adverse effects. For example, warfarin is not combined with aspirin as it may cause bleeding.
Absolute contraindication: This means that the medication could cause a life-threatening situation. Hence, the medication must be avoided. Examples are isotretinoin, which is contraindicated in pregnancy due to the high risk of birth defects; sildenafil, which is contraindicated with nitrates due to severe hypotension; cisapride, which is contraindicated with multiple drugs, including macrolides like erythromycin, antifungals like fluconazole, and protease inhibitors like ritonavir; and MAO inhibitors, which are contraindicated with SSRIs.
Drugs contraindicated in pregnancy: Many medications may cause birth defects and fetal loss if used during pregnancy especially during the first trimester. They include isotretinoin, blood pressure medications like ACE inhibitors and ARBs, antiepileptics like sodium valproate and valproic acid, phenytoin, carbamazepine, phenobarbital and topiramate, benzodiazepines, thalidomide,oral contraceptives, warfarin and ibuprofen.
Drugs contraindicated in old age: With old age organs like liver and kidney are not functioning optimally which increases the risk of adverse effects as these organs are major sites of drug metabolism and excretion. Changes in body fat, water and muscle mass with age also affect the distribution of drugs in the body. Beer’s criteria is used to determine safety of a medication in the elderly. Such medications may be OTC or prescription medications e.g. antipsychotics like haloperidol and risperidone, anticholinergics like amitriptyline, imipramine, dicyclomine and trihexyphenidyl, sleeping pills like zolpidem, zaleplon, benzodiazepines, muscle relaxants and OTC products containing diphenhydramine (Benadryl) and chlorpheniramine. Blood thinners like aspirin and antidiabetics like glyburide and glipizide must be used with caution as risk of adverse effects like bleeding and hypoglycemia are very high.
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