Prevalence and typology of potential drug interactions occurring in primary care patients

Figures & data

Table I. Presence of potential interactions according to different patient-dependent factors. Ratio of adjusted prevalence and confidence interval.

	Presence of interactions (%)
	Exposed	Non-exposed	Prevalence ratio	95% Confidence interval	Significance (P)
Number of medications prescribed^a	39.7	7.5	4.70	4.56–4.86	<0.0001
Presence of a chronic disease	26.8	11.8	1.54	1.49–1.60	<0.0001
Advanced age (over 65 years)	28.5	14.4	1.19	1.15–1.23	<0.0001
Gender, females	21.3	19.3	1.07	1.04–1.10	<0.0001

^aNumber of medications prescribed: exposed and non-exposed groups are differentiated according to their median (four prescriptions).

Table II. Number and type of potential interactions identified.

			Remedial action
			0Avoid association	1Patient surveillance	2Increase time interval	Total
Relevance	A	Relevant	6 227	9 949	2 366	18 542	55.1%
	B	Relevant in special circumstances	1 020	2 143	0	3 163	9.4%
	C	Potentially relevant	1 298	3 545	39	4 882	14.5%
	D	Low relevance	978	6 073	0	7 051	21.0%
		Total	9 523	21 710	2 405	33 638
			28.3%	64.5%	7.1%

Table III. Potential operational interactions with a frequency >1%.

Interaction: Operational type	%	% Ac.	Comments
NSAIDs + diuretics—D1	10.0	10.0	Decrease of the diurectic/antihypertensive effect due to inhibition of renal cyclooxygenase. The NSAIDs involved have limited affinity for this enzyme (for example, selective inhibitors of COX2), and/or are combined with a diuretic producing an interaction with no clinical relevance evidence.
Calcium + bisphosphonates—A2	6.0	15.9	Their concurrent administration may reduce bisphosphonate serum levels due to a decrease of it's oral absorption. These medications should be taken with at least one-hour margin between them.
NSAIDs + ACEI—D1	5.3	21.3	Decrease of the antihypertensive effect of ACEI by inhibition of prostaglandin synthesis at renal level. Excludes associations of NSAIDs and ACEIs with significant and well-documented interaction, for example with indomethacin or ibuprofen with captopril.
Inhaled selective beta-2 agonists + diuretics—A1adrenergic	4.7	26.0	Reinforcement of the hypokalaemic action of beta-2 drugs by non-potassium sparing diuretics, with risk of tachycardia and other dysrhythmias.
Clopidogrel + ASA (cardio)—C1	3.8	29.8	Possible reinforcement of the collagen-induced platelet-aggregation inhibitory effect of ASA. Although no clinical evidence is available, the safety of the concurrent administration of these medications has not been established, and caution is recommended when used concomitantly.
Benzodiazepines + Omeprazole—A0^a	3.4	33.2	Omeprazole inhibits the hepatic metabolism of benzodiazepines at the P450 cytochrome level. When used in association with benzodiazepines requiring this metabolic step(diazepam, bipotassic chlorazepate, etc.), it leads to an increase in serum levels and possible intoxication.
Diuretics + digoxin—A1	2.8	36.0	Possible increase in digoxin toxicity when combined with non-potassium sparing diuretics, leading to a decrease in potassium serum levels.
Calcium + thiazides and analogues—A0^a	2.3	38.3	Possible accumulation of calcium in the body due to inhibition of its urinary excretion that may lead to toxic effects.
Acenocoumarol + Omeprazole—A1	2.3	40.6	Possible reinforcement of the anticoagulant effect due to inhibition of hepatic metabolism.
NSAIDs + diuretics—A0^a	2.1	42.7	Loss of the diuretic/antihypertensive effect due to renal cyclooxygenase inhibition. There is extensive clinical evidence of interaction with the NSAIDs involved (for example, indomethacin) and/or combined with potent diuretics (for example, loop diuretics).
Inhaled selective beta-2 agonists + glucocorticoids—A1	2.1	44.8	Reinforcement of the hypokalaemic action of beta-2 adrenergic drugs by glucocorticoids, with risk of tachycardia and other dysrhythmias.
Sulfonylurea + thiazide and analogues—B1	2.1	46.9	Decrease of the hypoglycaemic effect of sulfonylureas, and risk of hyperglycemia due to a diminished insulin release as a consequence of the hypokalaemic effect of thiazides.
Allopurinol + thiazides and analogues—A1	1.8	48.7	Occasional occurrence of significant allergic reactions of unknown mechanism.
Angiotensin II antagonists + potassium sparing diuretics—D1	1.3	50.1	Possible occurrence of toxicity due to hyperkalaemia, by addition of the potassium-sparing effect of both drug classes.
Digoxin + proton pump inhibitors—C1	1.3	51.4	Possible accumulation in the body and toxicity of digoxin that may be due to increased gastrointestinal absorption as a consequence of the increased gastric pH produced by proton pump inhibitors.
Acenocoumarol + ASA (cardio)—A0^a	1.2	52.5	Reinforced anticoagulant effect with risk of bleeding. The association must be avoided, except in selected patients for whom a consensus has been reached, for example those with cardiac prosthesis and suffering CVA in spite of an adequate INR.
Benzodiazepines + serotonin selective reuptake inhibitors—A1	1.1	53.7	Possible increase of plasma levels and benzodiazepine toxicity due to inhibition of the hepatic metabolism when associated with certain serotonin selective reuptake inhibitors, included fluoxetine or fluvoxamine.

^aA0 type interactions.

% Ac: accumulated percentage.

NSAIDs, non-steroidal anti-inflammatory drugs; ACEIs, angiotensin converter enzyme inhibitors; ASA (cardio), anti-aggregative doses of acetylsalicylic acid.