increases the exposure to rupatadine. Avoid.

Study

▶ HIV-protease inhibitors are predicted to increase the exposure

to mizolastine. Avoid.rStudy

▶ HIV-protease inhibitors are predicted to increase the exposure

to rupatadine. Avoid.oStudy

▶ Idelalisib is predicted to increase the exposure to mizolastine.

Avoid.rStudy

▶ Idelalisib is predicted to increase the exposure to rupatadine.

Avoid.oStudy

▶ Imatinib

r

is predicted to increase the exposure to mizolastine.

Theoretical

▶ Imatinib is predicted to increase the exposure to rupatadine.

Avoid.oStudy

▶ Lapatinib is predicted to increase the exposure to

fexofenadine.oTheoretical

▶ Leflunomide is predicted to increase the exposure to

fexofenadine.oStudy

▶ Letermovir is predicted to increase the concentration of

fexofenadine.oTheoretical

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to mizolastine. Avoid.rStudy

▶ Macrolides (clarithromycin, erythromycin) are predicted to

increase the exposure to rupatadine. Avoid.oStudy

▶ Macrolides (erythromycin) are predicted to increase the

exposure to mizolastine.rTheoretical

▶ Mirabegron is predicted to increase the exposure to

fexofenadine.nTheoretical

▶ Monoamine-oxidase A and B inhibitors, irreversible are

predicted to increase the risk of antimuscarinic side-effects

when given with

Theoretical

antihistamines, non-sedating. Avoid.r

▶ Netupitant

r

is predicted to increase the exposure to mizolastine.

Theoretical

▶ Netupitant is predicted to increase the exposure to rupatadine.

Avoid.oStudy

▶ Nilotinib

r

is predicted to increase the exposure to mizolastine.

Theoretical

▶ Nilotinib is predicted to increase the exposure to rupatadine.

Avoid.oStudy

▶ Pibrentasvir (with glecaprevir) is predicted to increase the

exposure to fexofenadine.oStudy

▶ Pitolisant is predicted to decrease the exposure to

fexofenadine.nTheoretical

▶ Rifampicin

o

is predicted to decrease the exposure to bilastine.

Theoretical

▶ Rifampicin

Study

increases the clearance of fexofenadine.o ▶ Teriflunomide is predicted to increase the exposure to

fexofenadine.oStudy

▶ Velpatasvir is predicted to increase the exposure to

fexofenadine.rTheoretical

▶ Venetoclax is predicted to increase the exposure to

fexofenadine.oTheoretical

BNF 78 Antifungals, azoles — Antihistamines, non-sedating 1407

Interactions | Appendix 1

A1

Antihistamines, sedating → see TABLE 9 p. 1377 (QT-interval

prolongation), TABLE 11 p. 1377 (CNS depressant effects), TABLE 10 p. 1377

(antimuscarinics)

GENERAL INFORMATION Drugs with antimuscarinic effects

might reduce the absorption of levodopa, see TABLE 10 p. 1377.

alimemazine . antazoline . buclizine . chlorphenamine . cinnarizine . clemastine . cyclizine . cyproheptadine . doxylamine . hydroxyzine . ketotifen . pizotifen . promethazine.

ROUTE-SPECIFIC INFORMATION Since systemic absorption can

follow topical application of ketotifen, the possibility of

interactions should be borne in mind.

▶ Hydroxyzine potentially increases the risk of overheating and

dehydration when given with antiepileptics (zonisamide). Avoid

in children.rTheoretical

▶ Antihistamines, sedating are predicted to decrease the effects

of betahistine.oTheoretical

▶ Cyproheptadine

o

decreases the effects of metyrapone. Avoid.

Study

▶ Monoamine-oxidase A and B inhibitors, irreversible are

predicted to increase the risk of antimuscarinic side-effects

when given with

Theoretical

antihistamines, sedating. Avoid.r

▶ Antihistamines, sedating are predicted to decrease the efficacy

of pitolisant.oTheoretical

▶ Cyproheptadine

o

potentially decreases the effects of SSRIs.

Anecdotal

Antimalarials → see TABLE 15 p. 1378 (myelosuppression), TABLE 9

p. 1377 (QT-interval prolongation)

artemether. artenimol . atovaquone . chloroquine . lumefantrine . mefloquine . piperaquine . primaquine . proguanil . pyrimethamine . quinine.

PHARMACOLOGY Piperaquine has a long half-life; there is a

potential for drug interactions to occur for up to 3 months

after treatment has been stopped.

▶ Chloroquine is predicted to decrease the effects of agalsidase.

Avoid.oTheoretical

▶ Antimalarials (chloroquine, primaquine) are predicted to

increase the risk of methaemoglobinaemia when given with

topical anaesthetics, local (prilocaine). Use with caution or

avoid.rTheoretical

▶ Antacids decrease the absorption of chloroquine. Separate

administration by at least 4 hours.oStudy

▶ Antacids are predicted to decrease the absorption of proguanil.

Separate administration by at least 2 hours.oStudy

▶ Antiarrhythmics (dronedarone) are predicted to increase the

concentration of piperaquine.rTheoretical

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to artemether (with lumefantrine). Avoid.rStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the

concentration of piperaquine. Avoid.oTheoretical

▶ Antiepileptics (carbamazepine, phenobarbital, primidone)

potentially increase the risk of toxicity when given with

quinine.qStudy

▶ Pyrimethamine increases the risk of haematological toxicity

when given with

Study

antiepileptics (fosphenytoin, phenytoin).r

▶ Pyrimethamine is predicted to increase the risk of

haematological toxicity when given with antiepileptics

(phenobarbital, primidone).rTheoretical

▶ Antifungals, azoles (fluconazole, isavuconazole, itraconazole,

ketoconazole, posaconazole, voriconazole) are predicted to

increase the concentration of piperaquine.rTheoretical

▶ Antifungals, azoles (fluconazole, itraconazole, posaconazole,

voriconazole) are predicted to increase the exposure to

mefloquine.oTheoretical

▶ Antifungals, azoles (ketoconazole) increase the exposure to

mefloquine.oStudy

▶ Antimalarials (proguanil) are predicted to increase the risk of

side-effects when given with

r

antimalarials (pyrimethamine).

Theoretical

▶ Aprepitant is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Mefloquine is predicted to increase the risk of bradycardia

when given with beta blockers, non-selective.rTheoretical

▶ Mefloquine is predicted to increase the risk of bradycardia

when given with beta blockers, selective.rTheoretical

▶ Mefloquine is predicted to increase the risk of bradycardia

when given with calcium channel blockers.rTheoretical

▶ Calcium channel blockers (diltiazem, verapamil) are predicted to

increase the concentration of piperaquine.rTheoretical

▶ Calcium salts (calcium carbonate) decrease the absorption of

chloroquine

o

. Separate administration by at least 4 hours.

Study

▶ Calcium salts (calcium carbonate) are predicted to decrease the

absorption of proguanil. Separate administration by at least

2 hours.oStudy

▶ Chloroquine

o

decreases the efficacy of oral cholera vaccine.

Study

▶ Cobicistat is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Crizotinib is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Antimalarials (chloroquine, primaquine) are predicted to

increase the risk of methaemoglobinaemia when given with

dapsone.rTheoretical

▶ Mefloquine is predicted to increase the risk of bradycardia

when given with digoxin.rTheoretical

▶ Quinine increases the concentration of digoxin. Monitor and

adjust digoxin dose, p. 109.rAnecdotal

▶ Efavirenz

Study → Also see

decreases the concentration of

TABLE 9 p. 1377

artemether.r

▶ Efavirenz moderately decreases the exposure to atovaquone.

Avoid.oStudy

▶ Efavirenz

Study

affects the exposure to proguanil. Avoid.o ▶ Enzalutamide is predicted to decrease the exposure to

artemether (with lumefantrine). Avoid.rStudy

▶ Enzalutamide is predicted to decrease the concentration of

piperaquine. Avoid.oTheoretical

▶ Etravirine

Study

decreases the exposure to artemether.o ▶ Grapefruit juice

q

increases the exposure to artemether.

Study

▶ Grapefruit juice is predicted to increase the concentration of

piperaquine. Avoid.rTheoretical

▶ H2 receptor antagonists (cimetidine) decrease the clearance of

chloroquine.oStudy

▶ H2 receptor antagonists (cimetidine) slightly increase the

exposure to quinine.oStudy

▶ HIV-protease inhibitors decrease the exposure to atovaquone.

Avoid if boosted with ritonavir.oStudy

▶ HIV-protease inhibitors are predicted to increase the

concentration of piperaquine.rTheoretical

▶ HIV-protease inhibitors are predicted to decrease the exposure

to proguanil. Avoid.oStudy

▶ HIV-protease inhibitors are predicted to affect the exposure to

quinine.rStudy → Also see TABLE 9 p. 1377

▶ Idelalisib is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Imatinib is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Lanthanum is predicted to decrease the absorption of

chloroquine

o

. Separate administration by at least 2 hours.

Theoretical

▶ Chloroquine is predicted to decrease the exposure to

laronidase

Theoretical

. Avoid simultaneous administration.r

▶ Macrolides (clarithromycin, erythromycin) are predicted to

increase the concentration of piperaquine.rTheoretical

▶ Mepacrine is predicted to increase the concentration of

primaquine. Avoid.oTheoretical

▶ Pyrimethamine is predicted to increase the risk of side-effects

when given with methotrexate.rTheoretical → Also see

TABLE 15 p. 1378

1408 Antihistamines, sedating — Antimalarials BNF 78

Interactions | Appendix 1

A1

▶ Metoclopramide decreases the concentration of atovaquone.

Avoid.oStudy

▶ Mitotane is predicted to decrease the exposure to artemether

(with lumefantrine). Avoid.rStudy

▶ Mitotane is predicted to decrease the concentration of

piperaquine. Avoid.oTheoretical

▶ Netupitant is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Nilotinib is predicted to increase the concentration of

piperaquine.rTheoretical

▶ Pyrimethamine is predicted to increase the risk of side-effects

when given with pemetrexed.rTheoretical → Also see

TABLE 15 p. 1378

▶ Chloroquine is predicted to increase the risk of haematological

toxicity when given with

Theoretical

penicillamine. Avoid.r

▶ Chloroquine moderately decreases the exposure to

praziquantel. Use with caution and adjust dose.oStudy

▶ Chloroquine

o

decreases the efficacy of rabies vaccine. Avoid.

Study

▶ Rifabutin slightly decreases the exposure to atovaquone.

Avoid.oStudy

▶ Rifampicin is predicted to decrease the exposure to artemether

(with lumefantrine). Avoid.rStudy

▶ Rifampicin moderately decreases the exposure to atovaquone

and atovaquone slightly increases the exposure to rifampicin.

Avoid.oStudy

▶ Rifampicin

r

moderately decreases the exposure to mefloquine.

Study

▶ Rifampicin is predicted to decrease the concentration of

piperaquine. Avoid.oTheoretical

▶ Rifampicin decreases the exposure to quinine.rStudy

▶ St John’s Wort is predicted to decrease the concentration of

piperaquine. Avoid.oTheoretical

▶ Pyrimethamine increases the risk of side-effects when given

with sulfonamides.rStudy → Also see TABLE 15 p. 1378

▶ Tetracyclines (tetracycline) decrease the concentration of

atovaquone.oStudy

▶ Pyrimethamine increases the risk of side-effects when given

with trimethoprim.rStudy

▶ Pyrimethamine is predicted to increase the risk of side-effects

when given with zidovudine.rTheoretical → Also see

TABLE 15 p. 1378

Antithymocyte immunoglobulin (rabbit) → see immunoglobulins

Apalutamide → see TABLE 9 p. 1377 (QT-interval prolongation)

▶ Apalutamide is predicted to decrease the exposure to

aldosterone antagonists

o

(eplerenone). Avoid or monitor.

Study

▶ Apalutamide potentially decreases the exposure to

antiepileptics (valproate).nTheoretical

▶ Antifungals, azoles (itraconazole, ketoconazole, voriconazole) are

predicted to increase the exposure to apalutamide.n

Study → Also see TABLE 9 p. 1377

▶ Apalutamide slightly decreases the exposure to antihistamines,

non-sedating (fexofenadine).nStudy

▶ Apalutamide is predicted to decrease the exposure to beta2

agonists (salmeterol). Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

bosutinib. Avoid or monitor.oStudy → Also see TABLE 9

p. 1377

▶ Apalutamide is predicted to decrease the exposure to

buspirone. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to calcium

channel blockers

o

(felodipine, lercanidipine). Avoid or monitor.

Study

▶ Clopidogrel is predicted to increase the exposure to

apalutamide.nStudy

▶ Cobicistat is predicted to increase the exposure to

apalutamide.nStudy

▶ Apalutamide is predicted to decrease the exposure to

colchicine.nStudy

▶ Apalutamide is predicted to decrease the exposure to

corticosteroids

o

(budesonide, fluticasone). Avoid or monitor.

Study

▶ Apalutamide is predicted to decrease the exposure to

coumarins. Avoid or monitor.nStudy

▶ Apalutamide is predicted to decrease the exposure to

dabigatran.nStudy

▶ Apalutamide is predicted to decrease the exposure to

darifenacin. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

dasatinib. Avoid or monitor.oStudy → Also see TABLE 9

p. 1377

▶ Apalutamide is predicted to decrease the exposure to

diazepam. Avoid or monitor.nStudy

▶ Apalutamide is predicted to decrease the exposure to digoxin.

nStudy

▶ Apalutamide is predicted to decrease the exposure to

everolimus. Avoid or monitor.oStudy

▶ Fibrates (gemfibrozil) are predicted to increase the exposure to

apalutamide.nStudy

▶ HIV-protease inhibitors are predicted to increase the exposure

to apalutamide.nStudy → Also see TABLE 9 p. 1377

▶ Idelalisib is predicted to increase the exposure to apalutamide.

nStudy

▶ Apalutamide is predicted to decrease the exposure to ivacaftor.

Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

lomitapide. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

lurasidone. Avoid or monitor.oStudy

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to apalutamide.nStudy → Also see TABLE 9 p. 1377

▶ Apalutamide is predicted to decrease the exposure to

maraviroc. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

methotrexate.nStudy

▶ Apalutamide markedly decreases the exposure to midazolam.

Avoid or monitor.rStudy

▶ Apalutamide is predicted to decrease the exposure to

moclobemide. Avoid or monitor.nStudy

▶ Apalutamide is predicted to decrease the exposure to

naloxegol. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to opioids

(alfentanil). Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

phosphodiesterase type-5 inhibitors (avanafil, sildenafil,

vardenafil). Avoid or monitor.oStudy → Also see TABLE 9

p. 1377

▶ Apalutamide is predicted to decrease the exposure to proton

pump inhibitors (lansoprazole, rabeprazole). Avoid or monitor.

nStudy

▶ Apalutamide markedly decreases the exposure to proton pump

inhibitors (omeprazole). Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

quetiapine. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to

sirolimus. Avoid or monitor.oStudy

▶ Apalutamide is predicted to decrease the exposure to SSRIs

(citalopram). Avoid or monitor.nStudy → Also see TABLE 9

p. 1377

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