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. Separate administration by at least 2 hours.

Study

▶ Oral magnesium decreases the absorption of bisphosphonates

(sodium clodronate). Avoid magnesium for 2 hours before or

1 hour after sodium clodronate.oStudy

▶ Intravenous magnesium potentially increases the risk of

hypotension when given with calcium channel blockers

(amlodipine, clevidipine, felodipine, lacidipine, lercanidipine,

nicardipine, nifedipine, nimodipine, verapamil) (in pregnant

women).rAnecdotal

▶ Intravenous magnesium increases the effects of neuromuscular

blocking drugs, non-depolarising.oStudy

▶ Intravenous magnesium is predicted to increase the effects of

suxamethonium.oStudy

Magnesium carbonate → see antacids

Magnesium trisilicate → see antacids

Maraviroc

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to maraviroc. Adjust dose.rStudy

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

predicted to markedly increase the exposure to maraviroc.

Adjust dose.rStudy

▶ Apalutamide is predicted to decrease the exposure to

maraviroc. Avoid or monitor.oStudy

▶ Aprepitant

o

is predicted to increase the exposure to maraviroc.

Study

▶ Bosentan is predicted to decrease the exposure to maraviroc.

Avoid.oTheoretical

▶ Cobicistat markedly increases the exposure to maraviroc. Refer

to specialist literature.rStudy

▶ Efavirenz decreases the exposure to maraviroc. Refer to

specialist literature.rTheoretical

▶ Enzalutamide is predicted to decrease the exposure to

maraviroc. Adjust dose.rStudy

▶ Etravirine (with a boosted protease inhibitor) increases the

exposure to maraviroc. Avoid or adjust dose.oStudy

▶ HIV-protease inhibitors (atazanavir, saquinavir) moderately to

markedly increase the exposure to maraviroc. Refer to

specialist literature.rStudy

▶ HIV-protease inhibitors (darunavir boosted with ritonavir)

markedly increase the exposure to maraviroc. Refer to

specialist literature.rStudy

▶ HIV-protease inhibitors (lopinavir boosted with ritonavir)

moderately increase the exposure to maraviroc. Refer to

specialist literature.rStudy

▶ HIV-protease inhibitors (ritonavir) markedly increase the

exposure to

Study

maraviroc. Refer to specialist literature.r

▶ Maraviroc potentially decreases the exposure to HIV-protease

inhibitors (fosamprenavir) and HIV-protease inhibitors

(fosamprenavir) potentially decrease the exposure to

maraviroc. Avoid.rStudy

▶ Idelalisib markedly increases the exposure to maraviroc.

Adjust dose.rTheoretical

▶ Macrolides (clarithromycin) are predicted to markedly increase

the exposure to maraviroc. Adjust dose.rStudy

▶ Mitotane is predicted to decrease the exposure to maraviroc.

Adjust dose.rStudy

▶ Netupitant

o

is predicted to increase the exposure to maraviroc.

Study

▶ Rifampicin is predicted to decrease the exposure to maraviroc.

Adjust dose.rStudy

▶ St John’s Wort is predicted to decrease the exposure to

maraviroc. Avoid.rTheoretical

Measles, mumps and rubella vaccine, live → see live vaccines

Mebendazole

▶ H2 receptor antagonists (cimetidine) increase the concentration

of mebendazole.oStudy

Medroxyprogesterone

▶ Sugammadex is predicted to decrease the exposure to

medroxyprogesterone. Use additional contraceptive

precautions.rTheoretical

Mefenamic acid → see NSAIDs

Mefloquine → see antimalarials

Melatonin → see TABLE 11 p. 1377 (CNS depressant effects)

▶ Antiepileptics (phenytoin) are predicted to decrease the

exposure to melatonin.oTheoretical

▶ Combined hormonal contraceptives are predicted to increase

the exposure to melatonin.oTheoretical

▶ HIV-protease inhibitors (ritonavir) are predicted to decrease the

exposure to melatonin.oTheoretical

1488 Macrolides — Melatonin BNF 78

Interactions | Appendix 1

A1

▶ Leflunomide is predicted to decrease the exposure to

melatonin.oTheoretical

▶ Mexiletine

o

is predicted to increase the exposure to melatonin.

Theoretical

▶ Quinolones (ciprofloxacin) are predicted to increase the

exposure to melatonin.oTheoretical

▶ Rifampicin

o

is predicted to decrease the exposure to melatonin.

Theoretical

▶ SSRIs (fluvoxamine) very markedly increase the exposure to

melatonin. Avoid.rStudy

▶ Teriflunomide is predicted to decrease the exposure to

melatonin.oTheoretical

Meloxicam → see NSAIDs

Melphalan → see alkylating agents

Memantine

▶ Dopamine receptor agonists (amantadine) increase the risk of

CNS toxicity when given with memantine. Use with caution or

avoid.rTheoretical

▶ Memantine is predicted to increase the effects of dopamine

receptor agonists (apomorphine, bromocriptine, cabergoline,

pergolide, pramipexole, quinagolide, ropinirole, rotigotine)

o .

Theoretical

▶ Memantine is predicted to increase the risk of CNS side-effects

when given with ketamine. Avoid.rTheoretical

▶ Memantine

o

is predicted to increase the effects of levodopa.

Theoretical

Mepacrine

▶ Mepacrine is predicted to increase the concentration of

antimalarials (primaquine). Avoid.oTheoretical

Mepivacaine → see anaesthetics, local

Meprobamate → see TABLE 11 p. 1377 (CNS depressant effects)

Meptazinol → see opioids

Mercaptopurine → see TABLE 1 p. 1375 (hepatotoxicity), TABLE 15

p. 1378 (myelosuppression)

▶ Allopurinol potentially increases the risk of haematological

toxicity when given with mercaptopurine. Adjust

mercaptopurine dose, p. 912.rStudy

▶ Mercaptopurine decreases the anticoagulant effect of

coumarins.oAnecdotal

▶ Febuxostat is predicted to increase the exposure to

mercaptopurine. Avoid.rTheoretical

▶ Live vaccines are predicted to increase the risk of generalised

infection (possibly life-threatening) when given with

mercaptopurine (high-dose). Public Health England advises

avoid (refer to Green Book).rTheoretical

Meropenem → see carbapenems

Mesalazine

ROUTE-SPECIFIC INFORMATION The manufacturers of some

mesalazine gastro-resistant and modified-release medicines

(Asacol MR tablets, Ipocol, Salofalk granules) suggest that

preparations that lower stool pH (e.g. lactulose) might

prevent the release of mesalazine.

Metaraminol → see sympathomimetics, vasoconstrictor

Metformin → see TABLE 14 p. 1378 (antidiabetic drugs)

▶ Alcohol (beverage)(excessive consumption) potentially

increases the risk of lactic acidosis when given with

metformin

Theoretical

. Avoid excessive alcohol consumption.o ▶ Bictegravir

o

slightly increases the exposure to metformin.

Study

▶ Dolutegravir increases the exposure to metformin. Use with

caution and adjust dose.rStudy

▶ Guanfacine is predicted to increase the concentration of

metformin.oTheoretical

▶ H2 receptor antagonists (cimetidine) increase the exposure to

metformin. Monitor and adjust dose.oStudy

▶ Mexiletine

q

is predicted to affect the exposure to metformin.

Theoretical

▶ Pitolisant is predicted to increase the exposure to metformin.

nTheoretical

▶ Ribociclib

o

is predicted to increase the exposure to metformin.

Theoretical

▶ Vandetanib increases the exposure to metformin. Monitor and

adjust dose.oStudy

Methadone → see opioids

Methenamine

▶ Acetazolamide is predicted to decrease the efficacy of

methenamine. Avoid.oTheoretical

▶ Potassium citrate is predicted to decrease the efficacy of

methenamine. Avoid.oTheoretical

▶ Sodium bicarbonate is predicted to decrease the efficacy of

methenamine. Avoid.oTheoretical

▶ Sodium citrate is predicted to decrease the efficacy of

methenamine. Avoid.oTheoretical

Methocarbamol → see TABLE 11 p. 1377 (CNS depressant effects)

Methotrexate → see TABLE 1 p. 1375 (hepatotoxicity), TABLE 15 p. 1378

(myelosuppression), TABLE 2 p. 1375 (nephrotoxicity), TABLE 5 p. 1375

(thromboembolism)

▶ Acetazolamide increases the urinary excretion of

methotrexate.oStudy

▶ Methotrexate is predicted to decrease the clearance of

aminophylline.oTheoretical

▶ Antiepileptics (levetiracetam) decrease the clearance of

methotrexate.rAnecdotal

▶ Antimalarials (pyrimethamine) are predicted to increase the risk

of side-effects when given with

Theoretical → Also see TABLE 15 p. 1378

methotrexate.r

▶ Apalutamide is predicted to decrease the exposure to

methotrexate.nStudy

▶ Asparaginase

Anecdotal → Also see

affects the ef

TABLE 1 p. 1375

ficacy of

→ Also see

methotrexate

TABLE 15

.r

p. 1378

▶ Aspirin (high-dose) is predicted to increase the risk of toxicity

when given with methotrexate.rStudy

▶ Brigatinib potentially increases the concentration of

methotrexate.oTheoretical

▶ Crisantaspase

Anecdotal → Also see

affects the ef

TABLE 1 p. 1375

ficacy of

→ Also see

methotrexate

TABLE 15

.r

p. 1378

▶ Eltrombopag is predicted to increase the concentration of

methotrexate.oTheoretical

▶ Methotrexate potentially increases the risk of severe skin

reaction when given with topical

Anecdotal → Also see TABLE 15 p. 1378

fluorouracil

→ Also see TABLE 5

.r

p. 1375

▶ Leflunomide is predicted to increase the exposure to

methotrexate.oTheoretical → Also see TABLE 1 p. 1375 →

Also see TABLE 15 p. 1378

▶ Live vaccines are predicted to increase the risk of generalised

infection (possibly life-threatening) when given with

methotrexate (high-dose). Public Health England advises

avoid (refer to Green Book).rTheoretical

▶ Nitrous oxide potentially increases the risk of methotrexate

toxicity when given with methotrexate. Avoid.rStudy

▶ NSAIDs are predicted to increase the risk of toxicity when

given with methotrexate.rStudy → Also see TABLE 2 p. 1375

▶ Pegaspargase

Anecdotal → Also see

affects the ef

TABLE 1 p. 1375

ficacy of

→ Also see

methotrexate

TABLE 15

.r

p. 1378

▶ Penicillins are predicted to increase the risk of toxicity when

given with methotrexate.rAnecdotal → Also see TABLE 1

p. 1375

▶ Potassium aminobenzoate increases the concentration of

methotrexate.oTheoretical

▶ Proton pump inhibitors decrease the clearance of methotrexate

(high-dose). Use with caution or avoid.rStudy

▶ Quinolones (ciprofloxacin) potentially increase the risk of

toxicity when given with methotrexate.rAnecdotal

▶ Regorafenib is predicted to increase the exposure to

methotrexate.oTheoretical → Also see TABLE 15 p. 1378

▶ Retinoids (acitretin) are predicted to increase the

concentration of methotrexate. Avoid.oAnecdotal

▶ Rolapitant is predicted to increase the exposure to

methotrexate. Avoid or monitor.oStudy

▶ Methotrexate is predicted to decrease the efficacy of

sapropterin.oTheoretical

▶ Sulfonamides are predicted to increase the exposure to

methotrexate. Use with caution or avoid.rTheoretical →

Also see TABLE 15 p. 1378

▶ Tedizolid is predicted to increase the exposure to

methotrexate. Avoid.oTheoretical

▶ Methotrexate is predicted to increase the risk of toxicity when

given with tegafur.rTheoretical

BNF 78 Melatonin — Methotrexate 1489

Interactions | Appendix 1

A1

Methotrexate (continued)

▶ Teriflunomide is predicted to increase the exposure to

methotrexate.oStudy

▶ Methotrexate

o

decreases the clearance of theophylline.

Study

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

when given with methotrexate. Avoid.rTheoretical → Also

see TABLE 2 p. 1375

Methoxyflurane → see volatile halogenated anaesthetics

Methyldopa → see TABLE 8 p. 1376 (hypotension)

▶ Entacapone is predicted to increase the exposure to

methyldopa.oTheoretical

▶ Iron (oral) decreases the effects of methyldopa.oStudy

▶ Methyldopa increases the risk of neurotoxicity when given

with lithium.rAnecdotal

▶ Monoamine-oxidase A and B inhibitors, irreversible are

predicted to alter the antihypertensive effects of methyldopa.

Avoid.rTheoretical → Also see TABLE 8 p. 1376

Methylphenidate

▶ Methylphenidate is predicted to decrease the effects of

apraclonidine. Avoid.rTheoretical

▶ Methylphenidate is predicted to increase the risk of elevated

blood pressure when given with

Theoretical

linezolid. Avoid.r

▶ Methylphenidate is predicted to increase the risk of a

hypertensive crisis when given with

Theoretical

moclobemide.r

▶ Methylphenidate is predicted to increase the risk of a

hypertensive crisis when given with monoamine-oxidase A and

B inhibitors, irreversible. Avoid and for 14 days after stopping

the MAOI.rTheoretical

▶ Monoamine-oxidase B inhibitors (rasagiline, selegiline) are

predicted to increase the risk of a hypertensive crisis when

given with methylphenidate. Avoid.rTheoretical

▶ Methylphenidate increases the risk of dyskinesias when given

with paliperidone.rTheoretical

▶ Risperidone increases the risk of dyskinesias when given with

methylphenidate.rAnecdotal

Methylprednisolone → see corticosteroids

Methylthioninium chloride → see TABLE 13 p. 1378 (serotonin

syndrome)

▶ Methylthioninium chloride is predicted to increase the risk of

r

severe hypertension when given with bupropion. Avoid.

Theoretical → Also see TABLE 13 p. 1378

Metoclopramide

▶ Metoclopramide is predicted to increase the risk of

methaemoglobinaemia when given with topical anaesthetics,

local (prilocaine). Avoid.rTheoretical

▶ Metoclopramide potentially decreases the absorption of

antifungals, azoles

Study

(posaconazole) (oral suspension).o ▶ Metoclopramide decreases the concentration of antimalarials

(atovaquone). Avoid.oStudy

▶ Metoclopramide is predicted to decrease the effects of

dopamine receptor agonists (apomorphine, bromocriptine,

cabergoline, pergolide, pramipexole, quinagolide, ropinirole,

rotigotine). Avoid.oStudy

▶ Metoclopramide

o

decreases the effects of levodopa. Avoid.

Study

▶ Metoclopramide is predicted to increase the effects of

neuromuscular blocking drugs, non-depolarising

Theoretical

.o ▶ Metoclopramide

o

increases the effects of suxamethonium.

Study

Metolazone → see thiazide diuretics

Metoprolol → see beta blockers, selective

Metronidazole → see TABLE 12 p. 1378 (peripheral neuropathy)

ROUTE-SPECIFIC INFORMATION Since systemic absorption can

follow topical application, the possibility of interactions

should be borne in mind.

▶ Alcohol (beverage) potentially causes a disulfiram-like

reaction when given with metronidazole. Avoid for at least

48 hours stopping treatment.oStudy

▶ Metronidazole increases the risk of toxicity when given with

alkylating agents (busulfan).rStudy

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the exposure to metronidazole.oStudy

▶ Metronidazole is predicted to increase the risk of capecitabine

toxicity when given with capecitabine.rTheoretical

▶ Metronidazole increases the anticoagulant effect of coumarins.

Monitor INR and adjust dose.rStudy

▶ Disulfiram increases the risk of acute psychoses when given

with metronidazole.rStudy → Also see TABLE 12 p. 1378

▶ Metronidazole increases the risk of toxicity when given with

fluorouracil.rStudy

Metyrapone

▶ Antiepileptics (fosphenytoin, phenobarbital, phenytoin,

primidone) are predicted to decrease the effects of

metyrapone. Avoid.oStudy

▶ Antihistamines, sedating (cyproheptadine) decrease the effects of

metyrapone. Avoid.oStudy

▶ Carbimazole

o

decreases the effects of metyrapone. Avoid.

Theoretical

▶ Combined hormonal contraceptives decrease the effects of

metyrapone. Avoid.oTheoretical

▶ Phenothiazines (chlorpromazine) decrease the effects of

metyrapone. Avoid.oTheoretical

▶ Propylthiouracil is predicted to decrease the effects of

metyrapone. Avoid.oTheoretical

▶ Tricyclic antidepressants (amitriptyline) decrease the effects of

metyrapone. Avoid.oTheoretical

Mexiletine

FOOD AND LIFESTYLE Dose adjustment might be necessary if

smoking started or stopped during treatment.

▶ Mexiletine is predicted to increase the exposure to

agomelatine.oStudy

▶ Mexiletine is predicted to increase the exposure to

aminophylline. Adjust dose.oTheoretical

▶ Mexiletine

o

is predicted to increase the exposure to anagrelide.

Theoretical

▶ Mexiletine increases the risk of torsade de pointes when given

with antiarrhythmics. Avoid.rTheoretical

▶ Antiepileptics (phenytoin) are predicted to increase the

clearance of

Study

mexiletine. Monitor and adjust dose.o ▶ Mexiletine potentially increases the risk of cardiovascular

side-effects when given with beta blockers, non-selective.

Avoid or monitor.rTheoretical

▶ Mexiletine potentially increases the risk of cardiovascular

side-effects when given with beta blockers, selective. Avoid or

monitor.rTheoretical

▶ Bupropion

o

is predicted to increase the exposure to mexiletine.

Study

▶ Mexiletine increases the risk of cardiovascular side-effects

when given with calcium channel blockers (diltiazem). Avoid or

monitor.rTheoretical

▶ Mexiletine potentially increases the risk of cardiovascular

side-effects when given with calcium channel blockers

(verapamil). Avoid or monitor.rTheoretical

▶ Cinacalcet

o

is predicted to increase the exposure to mexiletine.

Study

▶ Mexiletine increases the concentration of clozapine. Monitor

side effects and adjust dose.rStudy

▶ Cobicistat

r

potentially increases the exposure to mexiletine.

Theoretical

▶ Mexiletine potentially affects the exposure to coumarins

(warfarin). Avoid.qTheoretical

▶ Mexiletine is predicted to increase the exposure to dopamine

receptor agonists (ropinirole). Adjust dose.oStudy

▶ Mexiletine slightly increases the exposure to erlotinib. Monitor

side effects and adjust dose.oStudy

▶ HIV-protease inhibitors (ritonavir) are predicted to increase the

clearance of

Study

mexiletine. Monitor and adjust dose.o ▶ Leflunomide is predicted to increase the clearance of

mexiletine. Monitor and adjust dose.oStudy

▶ Mexiletine

q

potentially affects the exposure to lithium. Avoid.

Theoretical

▶ Mexiletine is predicted to increase the exposure to loxapine.

Avoid.qTheoretical

1490 Methotrexate — Mexiletine BNF 78

Interactions | Appendix 1

A1

▶ Mexiletine

o

is predicted to increase the exposure to melatonin.

Theoretical

▶ Mexiletine

q

is predicted to affect the exposure to metformin.

Theoretical

▶ Mexiletine slightly increases the exposure to monoamineoxidase B inhibitors (rasagiline).oStudy

▶ Mexiletine is predicted to increase the exposure to olanzapine.

Adjust dose.oAnecdotal

▶ Opioids

o

potentially decrease the absorption of oral mexiletine.

Study

▶ Mexiletine is predicted to increase the exposure to pirfenidone.

Use with caution and adjust dose.oStudy

▶ Rifampicin is predicted to increase the clearance of mexiletine.

Monitor and adjust dose.oStudy

▶ Mexiletine

o

is predicted to increase the exposure to riluzole.

Theoretical

▶ Mexiletine

o

is predicted to increase the exposure to roflumilast.

Theoretical

▶ SSRIs (fluoxetine, fluvoxamine, paroxetine) are predicted to

increase the exposure to mexiletine.oStudy

▶ Terbinafine

o

is predicted to increase the exposure to mexiletine.

Study

▶ Teriflunomide is predicted to increase the clearance of

mexiletine. Monitor and adjust dose.oStudy

▶ Mexiletine is predicted to increase the exposure to

theophylline. Monitor and adjust dose.oTheoretical

▶ Mexiletine

o

increases the exposure to tizanidine. Avoid.

Study

▶ Mexiletine is predicted to increase the exposure to

zolmitriptan

Theoretical

. Adjust zolmitriptan dose, p. 482.o

Mianserin → see TABLE 13 p. 1378 (serotonin syndrome), TABLE 11 p. 1377

(CNS depressant effects)

▶ Antiepileptics (carbamazepine) markedly decrease the exposure

to mianserin. Adjust dose.oStudy

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the exposure to mianserin.oStudy → Also see

TABLE 11 p. 1377

▶ Mianserin is predicted to increase the risk of toxicity when

given with moclobemide. Avoid and for 1 week after stopping

mianserin.rTheoretical → Also see TABLE 13 p. 1378

▶ Mianserin is predicted to increase the risk of toxicity when

given with monoamine-oxidase A and B inhibitors, irreversible.

Avoid and for 14 days after stopping the MAOI.

Theoretical → Also see TABLE 13 p. 1378

r

▶ Mianserin

o

is predicted to decrease the efficacy of pitolisant.

Theoretical

▶ Mianserin decreases the effects of sympathomimetics,

vasoconstrictor (ephedrine).rAnecdotal

Micafungin → see TABLE 1 p. 1375 (hepatotoxicity)

▶ Micafungin slightly increases the exposure to amphotericin.

Avoid or monitor toxicity.oStudy

Miconazole → see antifungals, azoles

Midazolam → see TABLE 11 p. 1377 (CNS depressant effects)

▶ Antiarrhythmics (dronedarone) are predicted to increase the

exposure to

r

midazolam. Monitor side effects and adjust dose.

Study

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to midazolam. Monitor and adjust dose.oStudy → Also

see TABLE 11 p. 1377

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to midazolam. Monitor

side effects and adjust dose.rStudy

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

predicted to markedly to very markedly increase the exposure

to midazolam. Avoid or adjust dose.rStudy

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

exposure to intravenous midazolam. Use with caution and

adjust dose.oTheoretical

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

exposure to oral midazolam. Avoid.oTheoretical

▶ Apalutamide markedly decreases the exposure to midazolam.

Avoid or monitor.rStudy

▶ Aprepitant is predicted to increase the exposure to midazolam.

Monitor side effects and adjust dose.rStudy

▶ Bosentan is predicted to decrease the concentration of

midazolam. Monitor and adjust dose.oTheoretical

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

increase the exposure to midazolam. Monitor side effects and

adjust dose.rStudy

▶ Cobicistat is predicted to markedly to very markedly increase

the exposure to midazolam. Avoid or adjust dose.rStudy

▶ Crizotinib is predicted to increase the exposure to midazolam.

Monitor side effects and adjust dose.rStudy

▶ Dabrafenib decreases the exposure to midazolam. Monitor and

adjust dose.oStudy

▶ Efavirenz

o

is predicted to alter the effects of midazolam. Avoid.

Theoretical

▶ Enzalutamide is predicted to decrease the exposure to

midazolam. Monitor and adjust dose.oStudy

▶ Fosaprepitant

o

slightly increases the exposure to midazolam.

Study

▶ HIV-protease inhibitors are predicted to markedly to very

markedly increase the exposure to midazolam. Avoid or adjust

dose.rStudy

▶ Idelalisib is predicted to markedly to very markedly increase

the exposure to midazolam. Avoid or adjust dose.rStudy

▶ Imatinib is predicted to increase the exposure to midazolam.

Monitor side effects and adjust dose.rStudy

▶ Letermovir slightly to moderately increases the exposure to

midazolam. Monitor and adjust dose.oStudy

▶ Lumacaftor is predicted to decrease the exposure to

midazolam. Avoid.rTheoretical

▶ Macrolides (clarithromycin) are predicted to markedly to very

markedly increase the exposure to midazolam. Avoid or adjust

dose.rStudy

▶ Macrolides (erythromycin) are predicted to increase the

exposure to

r

midazolam. Monitor side effects and adjust dose.

Study

▶ Mitotane is predicted to decrease the exposure to midazolam.

Monitor and adjust dose.oStudy

▶ Monoclonal antibodies (tocilizumab) are predicted to decrease

the exposure to

Theoretical

midazolam. Monitor and adjust dose.o ▶ Netupitant is predicted to increase the exposure to midazolam.

Monitor side effects and adjust dose.rStudy

▶ Nevirapine decreases the concentration of midazolam. Monitor

and adjust dose.oStudy

▶ Nilotinib is predicted to increase the exposure to midazolam.

Monitor side effects and adjust dose.rStudy

▶ Palbociclib

Study

increases the exposure to midazolam.o ▶ Ribociclib moderately increases the exposure to midazolam.

Avoid.oStudy

▶ Rifampicin is predicted to decrease the exposure to midazolam.

Monitor and adjust dose.oStudy

▶ Rucaparib slightly increases the exposure to midazolam.

Monitor and adjust dose.rStudy

▶ St John’s Wort moderately decreases the exposure to

midazolam. Monitor and adjust dose.oStudy

▶ Telotristat ethyl

o

decreases the exposure to midazolam.

Study

Midodrine → see sympathomimetics, vasoconstrictor

Midostaurin

▶ Antiarrhythmics (dronedarone) are predicted to increase the

exposure to midostaurin.oTheoretical

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to midostaurin. Avoid.rStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to

o

midostaurin.

Theoretical

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

predicted to very markedly increase the exposure to

midostaurin. Avoid or monitor for toxicity.rStudy

▶ Aprepitant is predicted to increase the exposure to

midostaurin.oTheoretical

BNF 78 Mexiletine — Midostaurin 1491

Interactions | Appendix 1

A1

Midostaurin (continued)

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

increase the exposure to midostaurin.oTheoretical

▶ Cobicistat is predicted to very markedly increase the exposure

to midostaurin. Avoid or monitor for toxicity.rStudy

▶ Crizotinib

o

is predicted to increase the exposure to midostaurin.

Theoretical

▶ Enzalutamide is predicted to decrease the exposure to

midostaurin. Avoid.rStudy

▶ HIV-protease inhibitors are predicted to very markedly increase

the exposure to

r

midostaurin. Avoid or monitor for toxicity.

Study

▶ Idelalisib is predicted to very markedly increase the exposure

to midostaurin. Avoid or monitor for toxicity.rStudy

▶ Imatinib

o

is predicted to increase the exposure to midostaurin.

Theoretical

▶ Macrolides (clarithromycin) are predicted to very markedly

increase the exposure to midostaurin. Avoid or monitor for

toxicity.rStudy

▶ Macrolides (erythromycin) are predicted to increase the

exposure to midostaurin.oTheoretical

▶ Mitotane is predicted to decrease the exposure to midostaurin.

Avoid.rStudy

▶ Netupitant is predicted to increase the exposure to

midostaurin.oTheoretical

▶ Nilotinib

o

is predicted to increase the exposure to midostaurin.

Theoretical

▶ Rifampicin is predicted to decrease the exposure to

midostaurin. Avoid.rStudy

▶ St John’s Wort is predicted to decrease the exposure to

midostaurin. Avoid.rTheoretical

Mifamurtide

▶ Ciclosporin is predicted to decrease the efficacy of

mifamurtide. Avoid.rTheoretical

▶ Corticosteroids are predicted to decrease the efficacy of

mifamurtide. Avoid.rTheoretical

▶ NSAIDs (high-dose) are predicted to decrease the efficacy of

mifamurtide. Avoid.rTheoretical

▶ Pimecrolimus is predicted to decrease the efficacy of

mifamurtide. Avoid.rTheoretical

▶ Sirolimus is predicted to decrease the efficacy of mifamurtide.

Avoid.rTheoretical

▶ Tacrolimus is predicted to affect the efficacy of mifamurtide.

Avoid.rTheoretical

Mifepristone

▶ Mifepristone is predicted to decrease the efficacy of

corticosteroids

Theoretical

. Use with caution and adjust dose.o

Minocycline → see tetracyclines

Minoxidil → see TABLE 8 p. 1376 (hypotension)

ROUTE-SPECIFIC INFORMATION Since systemic absorption can

follow topical application, the possibility of interactions

should be borne in mind.

Mirabegron

▶ Mirabegron is predicted to increase the exposure to aliskiren.

nTheoretical

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

predicted to increase the exposure to mirabegron. Adjust

mirabegron

o

dose in hepatic and renal impairment, p. 781.

Study

▶ Mirabegron is predicted to increase the exposure to

antihistamines, non-sedating (fexofenadine).nTheoretical

▶ Mirabegron is predicted to increase the exposure to beta

blockers, selective (metoprolol).oStudy

▶ Cobicistat is predicted to increase the exposure to mirabegron.

Adjust mirabegron dose in hepatic and renal impairment,

p. 781.oStudy

▶ Mirabegron is predicted to increase the exposure to colchicine.

nTheoretical

▶ Mirabegron is predicted to increase the exposure to

dabigatran.rTheoretical

▶ Mirabegron slightly increases the exposure to digoxin. Monitor

concentration and adjust dose.rStudy

▶ Mirabegron is predicted to increase the exposure to edoxaban.

nTheoretical

▶ Mirabegron is predicted to increase the exposure to eliglustat.

Avoid or adjust dose—consult product literature.rStudy

▶ Mirabegron is predicted to increase the exposure to

everolimus.nTheoretical

▶ HIV-protease inhibitors are predicted to increase the exposure

to mirabegron. Adjust mirabegron dose in hepatic and renal

impairment, p. 781.oStudy

▶ Idelalisib is predicted to increase the exposure to mirabegron.

Adjust mirabegron dose in hepatic and renal impairment,

p. 781.oStudy

▶ Mirabegron is predicted to increase the exposure to

loperamide.nTheoretical

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to mirabegron. Adjust mirabegron dose in hepatic

and renal impairment, p. 781.oStudy

▶ Mirabegron is predicted to increase the exposure to sirolimus.

nTheoretical

▶ Mirabegron is predicted to increase the exposure to taxanes

(paclitaxel).nTheoretical

▶ Mirabegron is predicted to increase the exposure to topotecan.

nTheoretical

Mirtazapine → see TABLE 13 p. 1378 (serotonin syndrome), TABLE 11

p. 1377 (CNS depressant effects)

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

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

p. 1377

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

predicted to increase the exposure to

Study

mirtazapine.o ▶ Cobicistat

o

is predicted to increase the exposure to mirtazapine.

Study

▶ Enzalutamide is predicted to decrease the exposure to

mirtazapine. Adjust dose.oStudy

▶ H2 receptor antagonists (cimetidine) slightly increase the

exposure to

o

mirtazapine. Use with caution and adjust dose.

Theoretical

▶ HIV-protease inhibitors are predicted to increase the exposure

to mirtazapine.oStudy

▶ Idelalisib

o

is predicted to increase the exposure to mirtazapine.

Study

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to mirtazapine.oStudy

▶ Mitotane is predicted to decrease the exposure to mirtazapine.

Adjust dose.oStudy

▶ Mirtazapine

o

is predicted to decrease the efficacy of pitolisant.

Theoretical

▶ Rifampicin is predicted to decrease the exposure to

mirtazapine. Adjust dose.oStudy

Mitomycin → see TABLE 15 p. 1378 (myelosuppression), TABLE 5 p. 1375

(thromboembolism)

▶ Live vaccines are predicted to increase the risk of generalised

infection (possibly life-threatening) when given with

mitomycin. Public Health England advises avoid (refer to

Green Book).rTheoretical

Mitotane → see TABLE 15 p. 1378 (myelosuppression)

▶ Mitotane is predicted to markedly decrease the exposure to

abemaciclib. Avoid.rStudy

▶ Mitotane is predicted to decrease the exposure to abiraterone.

Avoid.rStudy

▶ Aldosterone antagonists (spironolactone) are predicted to

decrease the effects of mitotane. Avoid.rAnecdotal

▶ Mitotane is predicted to decrease the exposure to aldosterone

antagonists (eplerenone). Avoid.oTheoretical

▶ Mitotane is predicted to decrease the exposure to alprazolam.

Adjust dose.oTheoretical

▶ Mitotane is predicted to decrease the exposure to

antiarrhythmics

Study

(disopyramide, dronedarone). Avoid.r

▶ Mitotane is predicted to decrease the efficacy of antiarrhythmics

(propafenone).oStudy

▶ Mitotane is predicted to decrease the exposure to

anticholinesterases, centrally acting (donepezil).nStudy

▶ Mitotane is predicted to decrease the exposure to antiepileptics

(perampanel). Monitor and adjust dose.oStudy

1492 Midostaurin — Mitotane BNF 78

Interactions | Appendix 1

A1

▶ Mitotane is predicted to decrease the exposure to antifungals,

azoles (isavuconazole). Avoid.rStudy

▶ Mitotane is predicted to decrease the exposure to antimalarials

(artemether) (with lumefantrine). Avoid.rStudy

▶ Mitotane is predicted to decrease the concentration of

antimalarials (piperaquine). Avoid.oTheoretical

▶ Mitotane is predicted to moderately decrease the exposure to

apixaban. Use with caution or avoid.rStudy

▶ Mitotane moderately decreases the exposure to apremilast.

Avoid.rStudy

▶ Mitotane is predicted to markedly decrease the exposure to

aprepitant. Avoid.oStudy

▶ Mitotane is predicted to moderately decrease the exposure to

aripiprazole. Adjust aripiprazole dose, p. 395.oStudy

▶ Mitotane is predicted to decrease the exposure to axitinib.

Avoid or adjust dose.oStudy → Also see TABLE 15 p. 1378

▶ Mitotane

Study

decreases the exposure to bedaquiline. Avoid.r

▶ Mitotane is predicted to decrease the exposure to bictegravir.

Avoid.oStudy

▶ Mitotane

r

slightly decreases the exposure to bortezomib. Avoid.

Study → Also see TABLE 15 p. 1378

▶ Mitotane affects the exposure to bosentan. Avoid.rStudy

▶ Mitotane is predicted to very markedly decrease the exposure

to bosutinib. Avoid.rStudy → Also see TABLE 15 p. 1378

▶ Mitotane is predicted to decrease the exposure to brigatinib.

Avoid.rStudy

▶ Mitotane is predicted to decrease the exposure to buspirone.

Use with caution and adjust dose.rStudy

▶ Mitotane moderately decreases the exposure to cabozantinib.

Avoid.oStudy → Also see TABLE 15 p. 1378

▶ Mitotane is predicted to decrease the exposure to calcium

channel blockers (amlodipine, felodipine, lacidipine,

lercanidipine, nicardipine, nimodipine). Monitor and adjust

dose.oStudy

▶ Mitotane is predicted to decrease the exposure to cannabis

extract. Avoid.rTheoretical

▶ Mitotane is predicted to decrease the exposure to cariprazine.

Avoid.rTheoretical

▶ Mitotane is predicted to decrease the exposure to ceritinib.

Avoid.rStudy → Also see TABLE 15 p. 1378

▶ Mitotane

Study

decreases the concentration of ciclosporin.r

▶ Mitotane

Theoretical

is predicted to alter the effects of cilostazol.o ▶ Mitotane is predicted to decrease the exposure to cinacalcet.

Monitor and adjust dose.oStudy

▶ Mitotane decreases the exposure to clomethiazole. Monitor

and adjust dose.oStudy

▶ Mitotane is predicted to decrease the exposure to cobicistat.

Avoid.rTheoretical

▶ Mitotane is predicted to decrease the exposure to cobimetinib.

Avoid.rTheoretical

▶ Mitotane is predicted to decrease the exposure to

corticosteroids (budesonide, deflazacort, dexamethasone,

fludrocortisone, hydrocortisone, methylprednisolone,

prednisolone, triamcinolone)

o

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