Potentially harmful drug-drug interactions in the elderly: a review.

Center for Health Outcomes and PharmacoEconomic Research, University of Arizona College of Pharmacy, Tucson, USA.
The American journal of geriatric pharmacotherapy 11/2011; 9(6):364-77. DOI: 10.1016/j.amjopharm.2011.10.004
Source: PubMed

ABSTRACT Elderly patients are vulnerable to drug interactions because of age-related physiologic changes, an increased risk for disease associated with aging, and the consequent increase in medication use.
The purpose of this narrative review was to describe findings from rigorously designed observational cohort and case-control studies that have assessed specific drug interactions in elderly patients.
The PubMed and International Pharmaceutical Abstracts databases were searched for studies published in English over the past 10 years (December 2000-December 2010) using relevant Medical Subject Headings terms (aged; aged, 80 and over; and drug interactions) and search terms (drug interaction and elderly). Search strategies were saved and repeated through September 2011 to ensure that the most recent relevant published articles were identified. Additional articles were found using a search of review articles and reference lists of the identified studies. Studies were included if they were observational cohort or case-control studies that reported specific adverse drug interactions, included patients aged ≥65 years, and evaluated clinically meaningful end points. Studies were excluded if they used less rigorous observational designs, assessed pharmacokinetic/pharmacodynamic properties, evaluated drug-nutrient or drug-disease interactions or interactions of drug combinations used for therapeutic benefit (eg, dual antiplatelet therapy), or had inconclusive evidence.
Seventeen studies met the inclusion criteria. Sixteen studies reported an elevated risk for hospitalization in older adults associated with adverse drug interactions. The drug interactions included: angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics, ACE inhibitors or angiotensin receptor blockers and sulfamethoxazole/trimethoprim, benzodiazepines or zolpidem and interacting medications, calcium channel blockers and macrolide antibiotics, digoxin and macrolide antibiotics, lithium and loop diuretics or ACE inhibitors, phenytoin and sulfamethoxazole/trimethoprim, sulfonylureas and antimicrobial agents, theophylline and ciprofloxacin, and warfarin and antimicrobial agents or nonsteroidal anti-inflammatory drugs. One study reported the risk for breast cancer-related death as a function of paroxetine exposure among women treated with tamoxifen.
Several population-based studies have reported significant harm associated drug interactions in elderly patients. Increased awareness and interventions aimed at reducing exposure and minimizing the risks associated with potentially harmful drug combinations are needed.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As a result of the chronic nature of epilepsy, patients often need concurrent therapy for other diseases. The benzodiazepines are frequently prescribed as anxiolytics, sedatives and hypnotics and these agents may interact with other drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as anti inflammatory, analgesic and antipyretic agents. They prescribed and used with diazepam in many clinical cases. In this study, convulsions were chemically induced in Albino mice by given picrotoxin (6 mg/kg). The animals were divided into several groups as following: picrotoxin, diazepam (1 mg/kg), aspirin (10, 100 & 200 mg/kg), diclofenac (10 & 20 mg/kg) and Celecoxib 20 mg/kg. All drugs were given intra peritoneally 30 minute before picrotoxin intake. In combination treatment, the NSAIDs were administrated 30 minute before diazepam; the latter was given 30 minute before picrotoxin. The following parameters were recorded: onset time in minutes, number of seizures (attacks) in each group and death occurrence within 24 hours after treatments. Administration of NSAIDs with diazepam showed that aspirin 200 mg/kg, diclofenac (in both doses) and celecoxib potentiated the effect of diazepam (p ≤ 0.001) while aspirin 10 mg/kg showed no effect on diazepam but aspirin 100 mg/kg reduced the anticonvulsant’s effect of diazepam (p ≤ 0.05). Thus, these findings may suggest that acute use of NSAIDs, of selective COX-2 inhibitors, but not nonselective COX inhibitors potentiate the effect of diazepam’s anticonvulsant effect and this interaction could be of pharmacodynamic type.
    Pharmacy & Pharmacology International Journal. 12/2014; 1(1):1-5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of Helicobacter pylori (H. pylori) infection and its complications increase with age. The majority of infected individuals remain asymptomatic throughout the life but 10%-20% develops peptic ulcer disease and 1% gastric malignancies. The incidence of ulcers and their complications are more common in the older population resulting in higher hospitalization and mortality rates. The increased use of medications causing gastric mucosal damage and the decreased secretion of protective prostaglandins in elderly are major factors increasing gastric mucosal sensitivity to the destructive effects of H. pylori. Due to higher prevalence of gastrointestinal (GI) malignancies, upper GI endoscopy is mostly preferred in elderly for the diagnosis of infection. Therefore, "endoscopy and treat" strategy may be more appropriate instead of "test and treat" strategy for dyspeptic patients in older age. Urea breath test and stool antigen test can be used for control of eradication, except for special cases requiring follow-up with endoscopy. The indications for treatment and suggested eradication regimens are similar with other age groups; however, the eradication failure may be a more significant problem due to high antibiotic resistance and low compliance rate in elderly. Multidrug usage and drug interactions should always be considered before starting the treatment. This paper reviews briefly the epidemiology, diagnosis, disease manifestations, and treatment options of H. pylori in the geriatric population.
    World journal of gastrointestinal pharmacology and therapeutics. 08/2014; 5(3):139-47.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs). A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer's disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities. Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and >2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications. Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.
    Clinical Interventions in Aging 01/2015; 10:269-75. · 2.65 Impact Factor

Full-text (3 Sources)

Available from
Jun 6, 2014