Dangerous drug combos that can be deadly

By Naveed Saleh, MD, MS
Published January 7, 2021

Key Takeaways

Millions of Americans purchase over-the-counter (OTC) medications without a second thought. But just because a drug can be obtained without a prescription doesn’t mean it is necessarily safe—especially if it’s taken in combination with prescription medications. 

According to an article in the Merck Manual, certain populations are highly susceptible to drug-drug interactions—in particular, those who are elderly, very young, ill, or pregnant. As such, physicians should closely monitor all drugs taken in these populations, including medications that don’t require a prescription.

Adverse drug effects can occur in any patient, but older adults are especially susceptible. They often take multiple drugs and have age-related changes in pharmacodynamics and pharmacokinetics—both of which increase the risk of adverse effects. And for elderly people, these effects can be serious: oversedation, confusion, hallucinations, falls, and bleeding.  

Increasingly, prescription drug labels specify whether different doses are needed for older people, pregnant women, children, or other vulnerable populations, but this information is rarely included on OTC drug labels. Because information on drug-drug interaction involving OTC medications is less publicized, it may be a good idea to consult with a pharmacist when in doubt.

Here are 10 notable interactions between OTC and prescription drugs. In the extreme, these interactions might be deadly.

Bismuth plus furosemide

Bismuth subsalicylate is an ingredient in OTC medications commonly used to treat diarrhea, upset stomach, heartburn, and nausea. Furosemide is used to treat hypertension, as well as edema in those with congestive heart failure, liver disease, and certain kidney disorders. When taken together, the adverse effects of bismuth and furosemide potentiate. Be on the lookout for bilateral lower extremity edema—particularly in those with pre-existing edema and cirrhosis. Clinicians should adjust dosages accordingly.

Thiazide diuretics and calcium salts

Thiazide diuretics are a commonly used hypertension treatment. Calcium salts (eg, calcium carbonate, calcium citrate) are used to supplement calcium in the diet, to prevent osteoporosis, and to treat cardiac arrest and hyperkalemia. This drug combination can result in hypercalcemia. Clinicians should monitor blood calcium levels and watch out for clinical indications of hypercalcemia including polydipsia, polyurea, abdominal pain, depression, fatigue, and muscle weakness. Patients should avoid excessive or prolonged intake of calcium salts.

NSAIDs and thiazide diuretics

NSAIDs, used to reduce pain, fever, and inflammation, can decrease the antihypertensive effects of thiazide diuretics by inducing sodium/water retention and inhibiting renal prostaglandin. Clinicians should keep an eye on blood pressure and adjust drug dosages accordingly.

Magnesium salts and sulfonylureas

Magnesium salts—also known as magnesium aluminum hydroxide—are commonly used for stomach upset, heartburn, and acid indigestion. They can boost absorption of sulfonylurea, used to treat type 2 diabetes, thus resulting in hypoglycemia. Blood sugar should be monitored with drug dosages adjusted accordingly.

Salicylates and insulin/sulfonylureas

Salicylates (aspirin) can boost insulin secretion and increase the efficacy of sulfonylureas. Clinicians should closely monitor serum glucose levels and adjust drug dosages as necessary.

Cimetidine or other H2 blockers, plus sulfonylureas

Cimetidine is a gastric acid reducer used in the treatment of ulcers. The combination of cimetidine and histamine 2 (H2) blockers, could result in lower liver metabolism of sulfonylureas, which, in addition to changes in gastric pH levels, could boost the effects of sulfonylurea. Blood glucose levels should be closely monitored, with drug dosages adjusted as needed.

Cimetidine and metformin

Cimetidine boosts concentrations of metformin, a type 2 diabetes treatment, by decreasing renal clearance, thus heightening the ability of metformin to clear glucose. Blood glucose levels should be monitored with either drug dosages adjusted or switching to an H2 blocker other than cimetidine.

Salicylates and niacin

Prescription niacin is used to treat high cholesterol, and aspirin is often taken with it to reduce the cutaneous flushing that can occur with niacin. However, aspirin can boost plasma concentrations of niacin, resulting in side effects, and niacin has been linked to liver damage and strokes, so physicians should monitor patients carefully.  

Antibiotics and antacids

Tetracyclines chelate with the metal ions in various antacids to form insoluble compounds, thus decreasing antibiotic absorption by more than 90%. With respect to the fluoroquinolones, ciprofloxacin, and ofloxacin, absorption is reduced by 50%-90% when paired with aluminum or magnesium hydroxide-containing antacids.

Warfarin and salicylates

Warfarin is an anticoagulant used to treat or prevent blood clots, which can reduce the risk of stroke, heart attack, or other serious conditions. Combining warfarin and salicylates (aspirin) can lead to increased bleeding compared with treatment with warfarin alone. But, that doesn’t mean that this combo should be avoided in all patients.

In a cross-sectional study, investigators publishing in the Anatolian Journal of Cardiology examined the co-administration of aspirin in patients with atrial fibrillation (AF) or mechanical-heart valves (MHV) on chronic warfarin therapy (>3 months).

“Although there is no doubt that every patient must be evaluated individually, the warfarin-aspirin combination appeared to be significantly overused in patients with AF, [the] main purpose being the prevention of cardiovascular events, and underused in patients with MHV, especially in patients with known arterial disease,” the authors concluded.

“Clinicians should be aware of additional antiplatelet therapy in patients using [oral anticoagulants] OACs. The need for combined anticoagulant-antiplatelet therapy should be questioned (or considered) in patients under OAC therapy based on individual thromboembolic and bleeding risks,” they added.

To read more about other types of drug-drug interactions, click here.

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