Potential drug interactions in cancer patients receiving supportive care exclusively

Cancer patients at the end of life often take many medications and are at risk for drug interactions. The purpose of this study was to describe the epidemiology of potential drug interactions in cancer patients receiving supportive care exclusively. We retrospectively reviewed the charts of consecutive adult cancer outpatients attending palliative care clinics at the Princess Margaret Hospital, Toronto, Canada. Drugs were screened for interactions by the Drug Interaction Facts software, which classifies interactions by levels of severity (major, moderate, and minor) and scientific evidence (1–5, with 1 = the strongest level of evidence). Among 372 eligible patients, 250 potential drug interactions were identified in 115 patients (31%, 95% confidence interval 26%–36%). The most common involved warfarin and phenytoin. Most interactions were classified as being of moderate severity (59%) and 42% of them were supported by Levels 1–3 of evidence. In multivariable analysis, increasing age (P < 0.001), presence of comorbidity (P = 0.001), cancer type (brain tumors, P < 0.001), and increasing number of drugs (P < 0.001) were associated with risk of drug interactions. Potential drug interactions are common in palliative care and mostly involve warfarin and anticonvulsants. Older patients, those with comorbid conditions, brain tumor patients, and those taking many medications are at greater risk of drug interactions.     

Pain in ambulatory HIV-infected patients with and without intravenous drug use

The prevalence of pain in 211 HIV-infected patients with and without intravenous drug use was assessed and the prognostic information inherent in pain reporting was evaluated, using a questionnaire on pain and HIV-related symptoms combined with data on disease classification, route of HIV transmission, CD4+ lymphocyte counts in blood (CD4) and mortality rates at 15 months after completing the questionnaire. The pain prevalence was significantly higher among intravenous drug users (IDUs) compared with non-IDUs [76/89 (85%) vs 87/122 (71%);p<0.05], especially among the patients classified as asymptomatic [43/53 (81%) vs 35/59 (59%);p = 0.01]. No significant difference was found among AIDS patients. In non-IDUs, a strong correlation was found between HIV disease stages according to the Centers for Disease Control classification (CDC) and pain prevalence (CDC A: 59%vs B: 74%vs C: 96%, p<0.001), and between the number of concurrent pain sites and both the CD4 levels (no pains: CD4 0.26 × 10⁹/l vs 1–2 pain sites: CD4 0.22 vs>2 pain sites: CD4 0.09;r = 0.35, p<0.001), and the mortality rate [no pains: 2/35 (6%) vs 1–2 pain sites: 8/45 (18%) vs> 2 pain sites: 12/42 (29%), p<0.01]. In IDUs, no such correlations were found. Our data demonstrates differences in the development, prevalence and prognostic value of pain among HIV-infected patients, with and without intravenous drug use, clearly indicating the need to differentiate risk groups in pain related studies.     

Potential drug-drug interactions in elderly patients presenting with syncope

Adverse drug reactions and interactions are a common cause of iatrogenic disease. Although there are resources available that have been developed for assessing potential drug-drug interactions (DDIs), one must first consider the possibility in order to apply these tools. This cross-sectional analysis of elderly patients evaluates Emergency Physician documentation of potential DDIs and assesses the utility of computer software recognition of interactions that can lead to syncope. In this study, lack of documentation of a patient's past medical history and medications suggests that Emergency Physicians are not evaluating DDIs as a possible source of their patient's symptoms. The computer resources evaluated were found to be easy to use and reliable. Rectifying and preventing potential DDIs can be an indispensible service provided by the Emergency Physician.     

Pharmacokinetic mechanisms of drug interactions.

Many patients require multiple-drug therapy, often under the supervision of several physicians, this increasing the risk of adverse drug effects. While drug interactions cannot always be conveniently categorized, familiarity with basic pharmacologic and pharmacokinetic principles permits the clinician to anticipate and avoid many of the more common and serious drug interactions. Most serious drug interactions involve one of the four pharmacokinetic processes governing drug behavior within the body: absorption, distribution, metabolism, and renal clearance. Knowledge of whether a drug is a weak acid or a weak base is clinically useful because it can alert the physician to the propensity for certain types of drug interactions.     

Urate excretion: drug interactions.

A derivative of probenecid, 2-nitroprobenecid, was studied in chimpanzees and Cebus monkeys. The uricosuria induced by the drug could be diminished by the infusion of p-aminohippurate (chimpanzee) or hippurate (monkey). Both hippurates inhibited the secretion of the drug and it is likely that the diminished response was the result of decreased access of 2-nitroprobenecid to its site of action. In contrast, pyrazinoate diminished the response to 2-nitroprobenecid without disturbing its renal disposition (both species). This action of pyrazinoate is attributed to its ability to inhibit the secretory flux of urate. The effect of pyrazinoate is diminished at high levels of 2-nitroprobenecid, i.e., it appears as if pyrazinoate causes a shift to the right of the concentration-response curve of 2-nitroprobenecid. A mathematical model is developed which seems to explain this apparent shift in the concentration-response curve. This model requires that the transepithelial fluxes for urate be very large. In the chimpanzee the action of salicylate resembles that of pyrazinoate but it is less prominent.     

Methotrexate and nonsteroidal antiinflammatory drug interactions.

OBJECTIVE: To determine if the coadministration of methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAIDs) results in a clinically significant drug interaction. DATA SOURCES: A case report of hematologic toxicity following the administration of MTX and flurbiprofen at our institution is presented. Six previously published case reports and five pharmacokinetic studies regarding MTX and NSAID interactions are available to assist in the evaluation of this potential interaction. DATA SYNTHESIS: Cases of various clinical manifestations during concomitant MTX and NSAID administration, including acute renal failure and pancytopenia, have been reported. The exact mechanism of the interaction has not been fully elucidated. Suggested theories to explain the mechanism of MTX toxicity include reduction in MTX clearance secondary to renal capillary constriction induced by NSAIDs, displacement of MTX or its metabolite from plasma proteins, competition between MTX and NSAIDs for renal tubular excretion, or impairment of hepatic metabolism of MTX by NSAIDs. Studies comparing MTX pharmacokinetics with or without concurrent NSAID therapy have not shown statistical differences in the parameters evaluated. However, one study did demonstrate differences in the pharmacokinetics of 7-hydroxy-methotrexate, the active metabolite of MTX, when MTX was administered with aspirin. CONCLUSIONS: Although a clinically significant interaction does not occur in all patients, numerous case reports are available that demonstrate possible problems following the coadministration of MTX and NSAIDs. To date, the specific circumstances during which the reaction may occur have not been well defined.