Table 1.

Queries relating to potential drug interactions involving bilastine fielded by the Medical Information Specialists at Faes Farma.

Drug	Potential interaction		Advice
Conventional anticoagulants
Acenocoumarol (ACN)	Interaction mainly via CYP 450; through displacement of ACN from its strong binding (98.7%) to plasma proteins; or through a reduction in vitamin K bioavailability.	BIL does not inhibit or induce CYP 450. No information is available regarding effects on plasma binding or vitamin K bioavailability.	SmPC for ACN notes that there is only a small risk of clinically significant DIs, but caution is always advised. The SmPC for BIL does not specify any risk of an interaction.
Novel Oral Anticoagulants (NOACs) and Antiplatelet Drugs
Dabigatran (DAB)	DAB is a substrate for the efflux P-gp transporter, which can be inhibited/induced by concomitant drug therapy.	BIL does not inhibit or induce P-gp. Like digoxin it acts as a P-gp substrate.	As for digoxin it is not expected that BIL will be associated with any relevant changes in exposure to DAB.
Rivaroxaban (RIV)	RIV is metabolised via CYP 3A4 or P-gp pathways, and inhibition of these is expected to increase RIV plasma levels.	BIL is not metabolised and does not inhibit or induce CYP 450.	It is not expected that BIL will be associated with any relevant changes in exposure to RIV.
Apixaban (API)	API is metabolised via CYP 3A4 or P-gp pathways, and inhibition of these is expected to increase API plasma levels.	The SmPC recommends that API should not be coadministered with strong inhibitors of CYP 3A4 or P-gp, such as azole antimycotics and HIV protease inhibitors. Strong inducers of CYP 3A4 or P-gp should be coadministered with caution.	It is not expected that BIL will be associated with any relevant changes in exposure to API.
Clopidogrel (CLO)	CLO is metabolised via CYP 2C19 to its active metabolite.	Whilst the clinical significance of this interaction is uncertain, concomitant treatment with moderate to strong inhibitors of CYP 2C19 should be avoided in patients receiving CLO.	Since BIL does not affect CYP 450 pathways it will be associated with any relevant changes in exposure to CLO.
Drugs used in the treatment of asthma or rhinitis
Chlorphenamine (CHL)	CHL is a first-generation sedating antihistamine, and the SmPC has a specific warning that it should not be used with other antihistamines.		There is no scientific evidence to support combining CHL and BIL, and if greater antihistamine effects are required (e.g. urticaria), then increasing the dose of BIL is recommended.
Steroids	Corticosteroids undergo very rapid metabolism in the liver.	BIL does not inhibit or induce CYP 450.	There are no apparent reasons to preclude the coadministration of BIL and corticosteroids if deemed appropriate by the physician.
Other drugs
Digoxin (DIG)	DIG is a cardiac glycoside used in the treatment of heart failure, and it has a narrow therapeutic window. It is a substrate for P-gp, the membrane-bound transporter enzyme. Drugs which inhibit P-gp will decrease the renal tubular elimination of DIG.	BIL is also a substrate for P-gp, but it does not inhibit its action. There is no scientific rationale why BIL would affect the bioavailability of DIG.	In the absence of clinical data, caution should be exercised when coadministering BIL and DIG, but the probability of an interaction seems low.
Antituberculosis drugs	Classically, drugs such as rifampicin, isoniazid, pyrazinamide, and ethambutol have been used in different combinations as first-line therapy. Second-and third-line treatments include aminoglycosides, quinolones, rifabutin and others. Many of these agents induce the efflux P-gp transporter and/or are eliminated via renal pathways.	The potential for these drugs to reduce the elimination of BIL and increase plasma levels cannot be ruled out.	Since pharmacokinetic data for BIL in combination with antitubercular drugs is not currently available, the doctor needs to carefully assess the overall risk-benefit if such treatment is being considered.
Antiretrovirals	There are a large number of available antiretroviral drugs, and they are used in different combinations. They have a narrow therapeutic window, and DIs may be important.	If metabolism is via CYP 450, then BIL will not usually have an effect. If combined with a P-gp inhibitor, there may be an increase in the bioavailability of bilastine, which is generally not clinically significant, but caution should be exercised in patients with renal impairment.	To make an informed choice based on a risk-benefit assessment, the doctor needs to know the precise antiretroviral regimen the patient is receiving. BIL should not be administered when they have renal impairment and are receiving a drug which is a P-gp inhibitor.
Proton pump inhibitors (PPIs)	PPIs are inhibitors of CYP 450, and this explains many of their drug-drug interactions. Furthermore, PPIs also inhibit P-gp, but this effect does not appear to be clinically relevant.	BIL is not metabolised and is unlikely to be affected by concomitant PPI therapy.	No interaction between BIL and PPIs is anticipated.
Oral contraceptives (OCs)	OCs are metabolised by CYP 450, and this explains many of their drug-drug interactions and the potential risk of an unwanted pregnancy. In addition, OCs inhibit CYP 450, and this might interfere with the metabolism of other drugs.	BIL does not inhibit or induce CYP 450. Furthermore, BIL is not metabolised, and so OCs cannot interfere with their elimination.	No interaction between BIL and OCs is anticipated. Women included in the clinical trials’ programme were required to use an effective contraceptive method, including OCs, and no interactions were observed.

Abbreviations: ACN = acenocoumarol; API = apixaban; BIL = Bilastine; CHL = chlorphenamine; CLO = clopidogrel; CYP 450 = cytochrome 450; DAB = dabigatran; DI = drug interactions; DIG = digoxin; NOACs = Novel Oral Anticoagulants; OCs = oral contraceptives; PPIs = proton pump inhibitors; P-gp = p-glycoprotein; RIV = rivaroxaban; SmPC = summary of product characteristics.