PRACTICE RECOMMENDATIONS
Be sure to inquire about over-the-counter drugs, herbal remedies, vitamins, and supplements when taking a medication history. A
Use an electronic prescribing software system that flags potential drug-drug interactions. A
Consider adjusting a dosing regimen or temporarily discontinuing a maintenance medication if the drug you are about to prescribe is likely to interact with another agent the patient is taking (and there are no alternatives you can prescribe). B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE John L, a 63-year-old man taking lovastatin (40 mg/d) and ramipril (5 mg/d) for hypercholesterolemia and arterial hypertension was hospitalized with atrial fibrillation. Three days later, he was discharged, with a prescription for amiodarone (200 mg/d). After a month, he was readmitted to the hospital with dark urine and intensifying thigh weakness and achiness. Laboratory testing revealed aspartate aminotransferase and alanine aminotransferase levels 10 times the upper limit of normal, and elevated urine and serum myoglobin.
Drug-drug interactions (DDIs) like the one John experienced between lovastatin and amiodarone are a common cause of readmissions, as well as emergency department visits and hospitalizations, for everything from myopathy to electrolyte imbalance, gastrointestinal (GI) bleeding, hepatotoxicity, renal dysfunction, and changes in blood pressure and heart rate.1-3
Yet many, if not most, DDIs can be avoided. With diligence and the right tools, you can do much to reduce the incidence of such interactions and adverse outcomes.
Polypharmacy and age pose the highest risks
The more medications a patient is taking, of course, the greater the likelihood of a clinically significant DDI. According to 1 study, 13% of patients taking 2 drugs develop a DDI; the incidence approaches 40% for patients taking 5 drugs, and exceeds 80% for patients taking 7 or more medications.4
In addition to polypharmacy, age alone is a key risk factor for DDIs.5 Pharmacokinetics and pharmacodynamics are frequently altered in older people, who may have slower intestinal transit time; diminished absorption capacity; decreased liver metabolism, mitochondrial function, and renal excretion; and alterations in volemia and body fat distribution.6 Although the speed at which these changes occur varies, aging is associated with a progressive deficiency in the regulation of most homeo-static mechanisms and an altered response to receptor stimulation.7
Whether age, multiple medications, or both are to blame, the impact on the elderly is striking. One recent retrospective study found 25% of elderly outpatients to be at risk for DDIs.8
Very young patients (<5 years) are also at risk for DDIs because of the immaturity of their enzymatic metabolic system.5,9,10 Additional risk factors, detailed in TABLE 1, include the presence of an infection or other acute medical condition, a metabolic or endocrine disorder, and taking 1 or more drugs with a narrow therapeutic range. Women are also at higher risk for DDIs than their male counterparts, the result of a slower metabolic capacity and interference with sex hormones.3-5,8,9 Pharmacogenetics may also play a big part in DDIs, and more and more studies are focusing on identifying patients at greatest risk.
TABLE 1
Risk factors for drug-drug interactions3-5,8,9
| Risk factor | Potential result |
|---|---|
| Acute medical condition (eg, dehydration, infection, alcoholism) | Augmented risk of elevated plasma drug concentration, increased catabolism, inhibition of hepatic drug metabolism |
| Age (very young [<5 years] and elderly) | Reduced metabolic capacity (greater accumulation of drugs) |
| Decreased renal and/or hepatic function | Decreased drug clearance/elimination; greater accumulation of drugs or their metabolites |
| Drug(s) with narrow therapeutic range | Increased risk for dose-related side effects |
| Female sex | Reduced metabolic capacity, interference with sex hormones |
| Metabolic or endocrine conditions (eg, fatty liver, obesity, hypothyroidism) | Altered hepatic metabolism, increased body distribution volumes, augmented risk of accumulation for hydrophobic molecules |
| Polypharmacy (≥3 medications) | Increased risk of metabolic and/or pharmacodynamic interference |
| Pharmacogenetics | Altered metabolic capacity (greater accumulation of drugs or their metabolites) |
Lack of coordinated care also increases risk
Another risk factor involves the use of multiple providers.9 A woman may be treated by—and receive prescriptions from—an endocrinolo-gist, a gynecologist, and a family physician (FP), for instance, and get medications from a local pharmacy, a nationwide discount chain, and a mail order pharmacy. As with the number of medications being taken, the greater the number of health care professionals a patient sees, the higher the risk.
To mitigate the risk, encourage your patients to fill all their prescriptions at the same pharmacy—and for your part, take a complete medication history before writing a new prescription.
Medication history in doubt? Schedule a “brown bag review”
Ask patients to provide the name and dose of every medication they’re taking. Inquire specifically about over-the-counter (OTC) cough and cold remedies and complementary and alternative medicines, including herbal remedies, vitamins, and supplements. Patients often neglect to mention nonprescription remedies and may not even think of them as medicine, but OTC products with the potential to interact adversely with prescription drugs may otherwise remain undetected.11-13