Associated factors of potential drug-drug interactions and drug-food interactions in patients with multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is the most common immune-mediated demyelinating disease in younger adults. Patients with MS (PwMS) are vulnerable to the presence of potential drug-drug interactions (pDDIs) and potential drug-food interactions (pDFIs) as they take numerous medications to treat MS, associated symptoms and comorbidities. Knowledge about pDDIs and pDFIs can increase treatment success and reduce side effects.

Objective: We aimed at determining the frequency and severity of pDDIs and pDFIs in PwMS, with regard to polypharmacy.

Methods: In the cross-sectional study, we analysed pDDIs and pDFIs of 627 PwMS aged ⩾18 years. Data collection was performed through patient record reviews, clinical examinations and structured patient interviews. pDDIs and pDFIs were identified using two DDI databases: Drugs.com Interactions Checker and Stockley's Interactions Checker.

Results: We identified 2587 pDDIs (counted with repetitions). Of 627 PwMS, 408 (65.1%) had ⩾ 1 pDDI. Polypharmacy (concomitant use of ⩾ 5 drugs) was found for 334 patients (53.3%). Patients with polypharmacy (Pw/P) were found to have a 15-fold higher likelihood of having ⩾ 1 severe pDDI compared with patients without polypharmacy (Pw/oP) (OR: 14.920, p < 0.001). The most frequently recorded severe pDDI was between citalopram and fingolimod. Regarding pDFIs, ibuprofen and alcohol was the most frequent severe pDFI.

Conclusion: Pw/P were particularly at risk of severe pDDIs. Age and educational level were found to be factors associated with the occurrence of pDDIs, independent of the number of medications taken. Screening for pDDIs/pDFIs should be routinely done by the clinical physician to increase drug safety and reduce side effects.

Keywords: multiple sclerosis; over-the-counter drugs; polypharmacy; potential drug–drug interactions; potential drug–food interactions.

Figure 1.

Percentage distribution of severity of drug–drug interactions in patients with MS. In this study, 627 MS patients had a total number of 2587 pDDIs. This chart shows the frequencies of the five pDDI severity levels. Most pDDIs were mild (57.1%), while moderate pDDIs had a share of 17.4%. Moderate-severe or severe interactions accounted for 12.9% of all interactions. MS, multiple sclerosis; pDDIs, potential drug–drug interactions.

Figure 2.

Comparison of the prevalence of pDDIs of different severity degrees between MS patients with and without polypharmacy. The proportion of patients having pDDIs was significantly higher in Pw/P versus Pw/oP for each degree of severity (Fisher’s exact test p < 0.001). Pw/P were three times more likely to have ⩾1 pDDI than Pw/oP (93.1% versus 33.1%). The distribution of the severity degrees was skewed towards more severe interactions in Pw/P as compared with Pw/oP (chi-square test p = 0.001). Pw/P had a roughly 10-fold higher risk of severe interactions. pDDIs were determined using Stockley’s Interactions Checker and Drugs.com Interactions Checker. Note that the patients could have several pDDIs of different severities at the same time. MS, multiple sclerosis; pDDIs, potential drug–drug interactions; Pw/oP, patients without polypharmacy; Pw/P, patients with polypharmacy.

Figure 3.

Interaction heatmap of drugs for which moderate-severe or severe pDDIs have been repeatedly noted in patients with MS. Shown is the frequency and severity of pDDIs between drugs involved in moderate-severe or severe pDDIs that were identified in at least three patients with MS (see also Table 4). The active ingredients are listed in alphabetical order. The size of the dots represents the frequency of pDDIs in the patient cohort (N = 627). The colour of the dots indicates the severity of the pDDI. The most common interaction has been recorded between interferon beta-1a and ibuprofen (29 patients). MS, multiple sclerosis; pDDIs, potential drug–drug interactions.

Figure 4.

Network of pDFIs for the top 20 drugs for which the most pDDIs were recorded. Grey dots stand for medications and blue dots represent other substances. The size of the grey dots shows the number of patients taking this drug (e.g. methylprednisolone was taken by 123 patients). The line colour indicates the severity of the interaction: green – mild interaction, yellow – moderate interaction and red – severe interaction. A total of 28 pDFIs were found between the top 20 drugs for which the most pDDIs were identified (Tables 3 and 5). Between those, there are 100 different pDDIs, which are not shown here for simplicity. A severe pDFI was found between ibuprofen and alcohol. Among the top 20 drugs, pantoprazole, torasemide, enoxaparin, hydrochlorothiazide and magnesium showed no interaction with alcohol, food or tobacco smoke. pDDIs, potential drug–drug interactions; pDFIs, potential drug–food interactions.