to tolvaptan. Use with caution or avoid depending on

indication.rStudy

▶ Antiepileptics (fosphenytoin, phenytoin) increase the clearance

of topotecan.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to toremifene. Adjust dose.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to trabectedin. Avoid.rTheoretical → Also see TABLE 1 p. 1375

▶ Carbamazepine decreases the concentration of trazodone.

Adjust dose.oAnecdotal

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the exposure to

Study

tricyclic antidepressants.o ▶ Carbamazepine decreases the exposure to tricyclic

antidepressants. Adjust dose.oStudy → Also see TABLE 18

p. 1379

▶ Tricyclic antidepressants (clomipramine, imipramine) potentially

increase the risk of overheating and dehydration when given

with zonisamide. Avoid in children.rTheoretical

▶ Trimethoprim increases the concentration of antiepileptics

(fosphenytoin, phenytoin).oStudy

▶ Antiepileptics (carbamazepine, eslicarbazepine, fosphenytoin,

oxcarbazepine, perampanel, phenobarbital, phenytoin,

primidone, rufinamide, topiramate) decrease the efficacy of

ulipristal. For FSRH guidance, see Contraceptives,

interactions p. 794.rAnecdotal

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to vandetanib. Avoid.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to moderately decrease

the exposure to velpatasvir. Avoid.rStudy

▶ Oxcarbazepine is predicted to decrease the exposure to

velpatasvir. Avoid.rTheoretical

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to vemurafenib. Avoid.rTheoretical

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to venetoclax. Avoid.rStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to

Theoretical

vinca alkaloids

→ Also see

(vinblastine, vincristine, vindesine)

TABLE 1 p. 1375 → Also see TABLE 12

.r

p. 1378

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to vinca alkaloids (vinflunine). Avoid.rTheoretical → Also see

TABLE 12 p. 1378

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to

r

vinca alkaloids (vinorelbine). Use with caution or avoid.

Theoretical → Also see TABLE 12 p. 1378

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to vismodegib. Avoid.oTheoretical

▶ Antiepileptics (fosphenytoin, phenytoin) decrease the effects of

vitamin D substances.oStudy

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the effects of

Theoretical

vitamin D substances.o ▶ Carbamazepine is predicted to decrease the effects of vitamin D

substances.oStudy

▶ Antiepileptics (phenobarbital, primidone) potentially increase

the risk of nephrotoxicity when given with volatile halogenated

anaesthetics (methoxyflurane). Avoid.rTheoretical → Also

see TABLE 11 p. 1377

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to vortioxetine. Monitor and adjust dose.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the

concentration of voxilaprevir. Avoid.rStudy

▶ Oxcarbazepine is predicted to decrease the concentration of

voxilaprevir. Avoid.rTheoretical

▶ Valproate

o

slightly increases the exposure to zidovudine.

Study

▶ Carbamazepine moderately decreases the exposure to

zolpidem.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to zopiclone. Adjust dose.oStudy → Also see TABLE 11

p. 1377

Antifungals, azoles → see TABLE 1 p. 1375 (hepatotoxicity), TABLE 9

p. 1377 (QT-interval prolongation)

clotrimazole . fluconazole .isavuconazole .itraconazole . ketoconazole . miconazole . posaconazole .voriconazole.

▶ Since systemic absorption can follow topical application,

the possibility of interactions with topical clotrimazole

and ketoconazole should be borne in mind.

▶ In general, fluconazole interactions relate to multiple-dose

treatment.

▶ The use of carbonated drinks, such as cola, improves

itraconazole, ketoconazole and posaconazole

bioavailability.

▶ Interactions of miconazole apply to the oral gel

formulation, as a sufficient quantity can be absorbed to

cause systemic effects. Systemic absorption from

intravaginal and topical formulations might also occur.

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to

o

abemaciclib.

Study

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

predicted to increase the exposure to abemaciclib. Avoid or

adjust abemaciclib dose, p. 967.rStudy

▶ Antifungals, azoles (itraconazole, ketoconazole) are predicted to

increase the exposure to afatinib. Separate administration by

12 hours.oStudy

▶ Alcohol (beverage) potentially causes a disulfiram-like

Anecdotal

reaction when given with ketoconazole. Avoid.o ▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to aldosterone

antagonists

Study

(eplerenone). Adjust eplerenone dose, p. 193.r

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

predicted to markedly increase the exposure to aldosterone

antagonists (eplerenone). Avoid.rStudy

▶ Itraconazole markedly increases the exposure to aliskiren.

Avoid.rStudy

▶ Ketoconazole

o

moderately increases the exposure to aliskiren.

Study

▶ Itraconazole increases the risk of busulfan toxicity when given

with

o

alkylating agents (busulfan). Monitor and adjust dose.

Study

▶ Miconazole is predicted to increase the concentration of

alkylating agents

o

(busulfan). Use with caution and adjust dose.

Theoretical

▶ Isavuconazole is predicted to increase the exposure to

alkylating agents (cyclophosphamide).oStudy

▶ Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

increase the exposure to almotriptan.nStudy

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

predicted to moderately increase the exposure to alpha

blockers

o

(alfuzosin, tamsulosin). Use with caution or avoid.

Study

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

predicted to increase the exposure to alpha blockers

(doxazosin).oStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to alpha blockers

(tamsulosin).oTheoretical

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to

Study

alprazolam.r

BNF 78 Antiepileptics — Antifungals, azoles 1399

Interactions | Appendix 1

A1

Antifungals, azoles (continued)

▶ Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

moderately increase the exposure to

o

alprazolam. Avoid.

Study

▶ Miconazole is predicted to increase the exposure to

alprazolam

Theoretical

. Use with caution and adjust dose.o ▶ Miconazole potentially decreases the exposure to

aminoglycosides (tobramycin).oAnecdotal

▶ Antacids decrease the absorption of itraconazole (capsule).

Antacids should be taken 1 hour before or 2 hours after

itraconazole.oStudy

▶ Antacids decrease the absorption of ketoconazole. Separate

administration by at least 2 hours.oStudy

▶ Miconazole is predicted to increase the exposure to

antiarrhythmics (disopyramide). Use with caution and adjust

dose.rTheoretical

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

predicted to increase the exposure to antiarrhythmics

(disopyramide). Avoid.rTheoretical → Also see TABLE 9

p. 1377

▶ Posaconazole is predicted to increase the exposure to

Theoretical

antiarrhythmics (disopyramide, dronedarone). Avoid.r

▶ Fluconazole is predicted to increase the exposure to

antiarrhythmics (dronedarone).rTheoretical → Also see

TABLE 9 p. 1377

▶ Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

very markedly increase the exposure to antiarrhythmics

(dronedarone). Avoid.rStudy → Also see TABLE 9 p. 1377

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to antiarrhythmics

(propafenone). Monitor and adjust dose.oStudy

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

predicted to increase the exposure to antiarrhythmics

(propafenone). Monitor and adjust dose.rStudy

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

predicted to increase the exposure to anticholinesterases,

centrally acting

o

(galantamine). Monitor and adjust dose.

Study

▶ Antiepileptics (carbamazepine) are predicted to decrease the

efficacy of fluconazole and fluconazole increases the

concentration of antiepileptics (carbamazepine). Avoid or

monitor carbamazepine concentration and adjust dose

accordingly, p. 311.rTheoretical → Also see TABLE 1 p. 1375

▶ Antiepileptics (carbamazepine) are predicted to decrease the

efficacy of ketoconazole and ketoconazole slightly increases

the concentration of antiepileptics (carbamazepine). Avoid or

monitor carbamazepine concentration and adjust dose

accordingly, p. 311.oStudy

▶ Antiepileptics (carbamazepine) are predicted to decrease the

efficacy of posaconazole and posaconazole increases the

concentration of

o

antiepileptics (carbamazepine). Avoid.

Theoretical

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to isavuconazole. Avoid.rStudy

▶ Antiepileptics (fosphenytoin) very markedly decrease the

exposure to itraconazole. Avoid and for 14 days after stopping

fosphenytoin.oStudy

▶ Antiepileptics (fosphenytoin) decrease the exposure to

voriconazole and voriconazole increases the exposure to

antiepileptics (fosphenytoin). Avoid or adjust voriconazole dose

and monitor phenytoin concentration, p. 599.oStudy

▶ Antiepileptics (fosphenytoin, phenytoin) decrease the exposure

to ketoconazole. Avoid.oStudy

▶ Antiepileptics (fosphenytoin, phenytoin) are predicted to

decrease the exposure to posaconazole. Avoid.oStudy

▶ Antiepileptics (phenobarbital) decrease the concentration of

itraconazole. Avoid and for 14 days after stopping

phenobarbital.oStudy

▶ Antiepileptics (phenobarbital) are predicted to decrease the

concentration of ketoconazole. Avoid.oStudy

▶ Antiepileptics (phenobarbital) are predicted to decrease the

concentration of posaconazole. Avoid.oStudy

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the concentration of

Theoretical

voriconazole. Avoid.o ▶ Antiepileptics (phenytoin) very markedly decrease the exposure

to itraconazole. Avoid and for 14 days after stopping

phenytoin.oStudy

▶ Antiepileptics (phenytoin) decrease the exposure to voriconazole

and voriconazole increases the exposure to antiepileptics

(phenytoin). Avoid or adjust voriconazole dose and monitor

phenytoin concentration, p. 599, p. 323.oStudy

▶ Antiepileptics (primidone) are predicted to decrease the

concentration of itraconazole.oTheoretical

▶ Miconazole increases the risk of carbamazepine toxicity when

given with antiepileptics (carbamazepine). Monitor and adjust

dose.rAnecdotal

▶ Miconazole increases the risk of phenytoin toxicity when given

with

r

antiepileptics (fosphenytoin). Monitor and adjust dose.

Anecdotal

▶ Fluconazole increases the concentration of antiepileptics

(fosphenytoin, phenytoin). Monitor concentration and adjust

dose.oStudy

▶ Antiepileptics (carbamazepine) are predicted to decrease the

efficacy of antifungals, azoles (itraconazole, voriconazole) and

antifungals, azoles (itraconazole, voriconazole) increase the

concentration of antiepileptics (carbamazepine). Avoid or

adjust dose.oTheoretical → Also see TABLE 1 p. 1375

▶ Antiepileptics (primidone) are predicted to decrease the

concentration of antifungals, azoles (ketoconazole,

posaconazole). Avoid.oStudy

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

predicted to very slightly increase the exposure to

antiepileptics (perampanel).nStudy

▶ Miconazole increases the risk of phenytoin toxicity when given

with

Anecdotal

antiepileptics (phenytoin). Monitor and adjust dose.r

▶ Antifungals, azoles (fluconazole) are predicted to increase the

exposure to antifungals, azoles (isavuconazole).rTheoretical

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

predicted to increase the exposure to antifungals, azoles

(isavuconazole). Avoid or monitor side effects.rStudy

▶ Antifungals, azoles (posaconazole) are predicted to increase the

exposure to

Theoretical

antifungals, azoles (isavuconazole).o ▶ Miconazole is predicted to increase the exposure to

antihistamines, non-sedating

Theoretical

(mizolastine). Avoid.o ▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to antihistamines, nonsedating (mizolastine).rTheoretical

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

predicted to increase the exposure to antihistamines, nonsedating (mizolastine). Avoid.rStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, itraconazole,

ketoconazole, posaconazole, voriconazole) are predicted to

increase the exposure to antihistamines, non-sedating

(rupatadine). Avoid.oStudy

▶ Ketoconazole increases the exposure to antimalarials

(mefloquine).oStudy

▶ Antifungals, azoles (fluconazole, itraconazole, posaconazole,

voriconazole) are predicted to increase the exposure to

antimalarials (mefloquine).oTheoretical

▶ Antifungals, azoles (fluconazole, isavuconazole, itraconazole,

ketoconazole, posaconazole, voriconazole) are predicted to

increase the concentration of

r

antimalarials (piperaquine).

Theoretical

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

predicted to increase the exposure to apalutamide.n

Study → Also see TABLE 9 p. 1377

▶ Itraconazole is predicted to increase the exposure to apixaban.

Avoid.rTheoretical

▶ Ketoconazole slightly to moderately increases the exposure to

apixaban. Avoid.rStudy

▶ Voriconazole is predicted to increase the exposure to apixaban.

Avoid.oTheoretical

1400 Antifungals, azoles — Antifungals, azoles BNF 78

Interactions | Appendix 1

A1

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

predicted to markedly increase the exposure to

o

aprepitant.

Study

▶ Fluconazole is predicted to increase the exposure to

aprepitant.oTheoretical

▶ Aprepitant is predicted to increase the exposure to

isavuconazole.oTheoretical

▶ Posaconazole is predicted to increase the exposure to

aprepitant.oStudy

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

predicted to slightly increase the exposure to aripiprazole.

Adjust aripiprazole dose, p. 395.oStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to

Theoretical

axitinib.o ▶ Antifungals, azoles (itraconazole, ketoconazole, voriconazole) are

predicted to increase the exposure to axitinib. Avoid or adjust

dose.oStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to bedaquiline. Avoid

prolonged use.nTheoretical → Also see TABLE 1 p. 1375 → Also

see TABLE 9 p. 1377

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

predicted to increase the exposure to bedaquiline. Avoid

prolonged use.nStudy → Also see TABLE 1 p. 1375 → Also see

TABLE 9 p. 1377

▶ Antifungals, azoles (itraconazole, ketoconazole) are predicted to

increase the exposure to

o