Retrospektivna analiza pojavnosti potencialnih in klinično izraženih interakcij med zdravili pri bolnikih z latentno okužbo z Mycobacterium tuberculosis

Brežan, Meta (author), Kerec - Kos, Mojca (mentor), Svetina, Petra (comentor)

Latentna tuberkulozna okužba (LTBO) je okužba z bakterijo iz skupine Mycobacterium tuberculosis complex, za katero je značilna odsotnost kliničnih simptomov in znakov bolezni. Pri osebah z LTBO in visokimi dejavniki tveganja za razvoj tuberkuloze je smiselno preventivno zdravljenje, pri čemer se v Sloveniji najpogosteje uporablja kombinacija rifampicina in izoniazida, ki lahko, zaradi delovanja na metabolizem sočasno apliciranih zdravil, povzroča interakcije med zdravili. Z raziskavo smo želeli ugotoviti pojavnost potencialnih in klinično izraženih interakcij pri bolnikih z LTBO, identificirati dejavnike, ki povečajo tveganje za klinično izražanje interakcij ter določiti časovni okvir izražanja interakcij. V raziskavo smo vključili bolnike, ki so se v obdobju med 1. 1. 2013 in 31. 12. 2015 ambulantno zdravili za LTBO na Univerzitetni kliniki za pljučne bolezni in alergijo Golnik ter prejemali sočasno sistemsko terapijo. Pregledali smo zdravstveno dokumentacijo bolnikov ter iz nje pridobili demografske podatke, podatke o poteku preventivnega zdravljenja ter podatke o klinično izraženih interakcijah. Potencialne interakcije smo identificirali s pomočjo programa Lexicomp®. V primeru klinično izraženih interakcij smo izračunali čas, v katerem so se te izrazile. Potencialne interakcije so bile prisotne pri 84,3 % (118/140) bolnikov zajetih v raziskavi in se klinično izrazile pri 18,6 % (22/118) bolnikov s potencialnimi interakcijami. Pri vseh klinično izraženih interakcijah je šlo za učinek rifampicina. Izrazile so se interakcije med rifampicinom in učinkovinami s protivnetnim in protibolečinskim delovanjem, antihipertenzivnimi učinkovinami ter zaviralci protonske črpalke. Največje število klinično izraženih interakcij je bilo z metilprednizolonom (7), metotreksatom (6) in paracetamolom (4). Starost in spol bolnikov, dolžina zdravljenja LTBO ter število sočasnih diagnoz in sočasno predpisanih učinkovin niso značilno vplivali na pogostost kliničnega izražanja interakcij. Od bolnikov z izraženimi interakcijami je imelo 72,7 % bolnikov postavljeno diagnozo bolezni vnetnega značaja. Mediana časa do nastopa klinično izraženih interakcij je bila 19,5 dni. Pri bolnikih z LTBO so potencialne interakcije pogoste, klinično pa so se izrazile le pri 18,6 % bolnikov. Pri bolnikih, ki se zdravijo za LTBO in prejemajo zdravila za zdravljenje vnetnih bolezni, kot so revmatoidni artritis, ankilozirajoči spondilitis, luskavica, artropatija in ulcerozni kolitis, bi bilo priporočljivo opraviti farmakoterapijski pregled pri kliničnem farmacevtu z namenom preprečevanja kliničnih posledic interakcij.

• Language: Slovenian
• Keywords: latentna tuberkulozna okužba, interakcije med zdravili, klinična izraženost, rifampicin, farmakoterapijski pregled
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-106892
• Publication date in RUL: 25.03.2019

Secondary language

• Language: English
• Title: Retrospective analysis of potential and actual drug - drug interactions incidence in patients with latent Mycobacterium tuberculosis infection

Abstract

Latent tuberculosis infection (LTBI) is infection with bacteria from Mycobacterium tuberculosis complex group with no clinical signs and symptoms. Due to the possibility of disease progression to an active state, individuals with high-risk factors should be treated for LTBI. In Slovenia a combination of rifampicin and isoniazid is usually used. These drugs affect metabolism of concomitant drug therapy and can cause drug-drug interactions. The aim of the study was to determine the incidence of potential and actual drug-drug interactions in out-patients with LTBI, to identify predictors of actual drug interactions and to determine a time frame of actual interaction manifestation. The study included out-patients who were treated for LTBI at the University Clinic of Respiratory and Allergic Diseases Golnik between 1. 1. 2013 and 31. 12. 2015 and were receiving concomitant systemic therapy. We examined patients’ medical documentation and collected their demographic data, data of their LTBI treatment and data on clinical manifestation of interactions. We identified potential drug interactions using Lexicomp®. In case of actual drug interactions, we calculated time in which they clinically manifested. Potential drug interactions were present in 84.3 % (118/140) of patients and were clinically manifested in 18.6 % (22/118) of patients with potential drug interactions. All actual drug interactions were due to rifampicin activity. Anti-inflammatory and analgesic drugs, antihypertensive drugs, and proton pump inhibitors were involved in actual drug interactions with rifampicin. Most of actual drug interactions included methylprednisolone (7), methotrexate (6), and paracetamol (4). Patients’ age and sex, duration of LTBI treatment, the number of concomitant diagnosis and the number of concomitant drugs did not statistically affect the prevalence of actual drug interactions. Among patients with actual drug interactions 72.7 % had a diagnosis of chronic inflammatory disease. Median time for clinical onset of actual drug interaction was 19.5 days. In out-patients with LTBI potential drug interactions are common, but were clinically manifested only in 18.6 % of patients. For patients treated for LTBI and at the same time receiving drugs for chronic inflammatory diseases, such as rheumatoid arthritis, ankylosing spondilitis, psoriasis, arthropathy and ulcerative colitis, a pharmacotherapy review at a clinical pharmacist would be recommended to prevent clinical consequences of drug-drug interactions.

• Keywords: latent tuberculosis infection, drug-drug interactions, clinical manifestation, rifampicin, pharmacotherapy review