theophylline. Monitor and adjust dose.

Theoretical

▶ Obeticholic acid is predicted to increase the exposure to

theophylline.rTheoretical

▶ Pentoxifylline increases the concentration of theophylline.

Monitor and adjust dose.rStudy

▶ Quinolones (ciprofloxacin) are predicted to increase the

exposure to

Theoretical

theophylline. Monitor and adjust dose.o ▶ Rifampicin is predicted to decrease the exposure to

theophylline. Adjust dose.oStudy

▶ Theophylline is predicted to slightly increase the exposure to

roflumilast. Avoid.oTheoretical

▶ Rucaparib is predicted to increase the exposure to

theophylline. Monitor and adjust dose.oStudy

▶ SSRIs (fluvoxamine) moderately to markedly increase the

exposure to theophylline. Avoid.rStudy

▶ St John’s Wort potentially decreases the exposure to

theophylline.rAnecdotal

▶ Sucralfate potentially decreases the absorption of

theophylline

o

. Separate administration by at least 2 hours.

Study

▶ Sympathomimetics, vasoconstrictor (ephedrine) increase the risk

of side-effects when given with theophylline. Avoid in

children.oStudy

▶ Teriflunomide is predicted to decrease the exposure to

theophylline. Adjust dose.oStudy

▶ Valaciclovir is predicted to increase the exposure to

theophylline.rTheoretical

Thiazide diuretics → see TABLE 18 p. 1379 (hyponatraemia), TABLE 8

p. 1376 (hypotension), TABLE 17 p. 1379 (reduced serum potassium)

bendroflumethiazide . chlorothiazide . chlortalidone . hydrochlorothiazide . hydroflumethiazide .indapamide . metolazone . xipamide. ▶ Thiazide diuretics are predicted to increase the risk of

hypersensitivity reactions when given with

Theoretical

allopurinol.r

▶ Aspirin (high-dose) increases the risk of acute renal failure

when given with thiazide diuretics.rTheoretical

▶ Thiazide diuretics increase the risk of hypercalcaemia when

given with calcium salts.rAnecdotal

▶ Thiazide diuretics increase the concentration of lithium. Avoid

or adjust dose and monitor concentration.rStudy

▶ NSAIDs increase the risk of acute renal failure when given with

thiazide diuretics.rTheoretical → Also see TABLE 18 p. 1379

▶ Reboxetine is predicted to increase the risk of hypokalaemia

when given with thiazide diuretics.oAnecdotal

▶ Thiazide diuretics are predicted to increase the risk of

hypercalcaemia when given with toremifene.rTheoretical

▶ Thiazide diuretics increase the risk of hypercalcaemia when

given with vitamin D substances.oTheoretical

Thiopental → see TABLE 8 p. 1376 (hypotension), TABLE 11 p. 1377 (CNS

depressant effects)

▶ Sulfonamides are predicted to increase the effects of

thiopental.oTheoretical

▶ Tricyclic antidepressants increase the risk of cardiac

arrhythmias and hypotension when given with

o

thiopental.

Study → Also see TABLE 8 p. 1376

Thiotepa → see alkylating agents

Thyroid hormones

levothyroxine . liothyronine. ▶ Antacids are predicted to decrease the absorption of

levothyroxine

o

. Separate administration by at least 4 hours.

Anecdotal

▶ Antiarrhythmics (amiodarone) are predicted to increase the risk

of thyroid dysfunction when given with thyroid hormones.

Avoid.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenytoin) are

predicted to increase the risk of hypothyroidism when given

with thyroid hormones.oStudy

▶ Antiepileptics (phenobarbital, primidone) are predicted to

decrease the effects of thyroid hormones.oTheoretical

▶ Apalutamide potentially decreases the exposure to

levothyroxine.nTheoretical

▶ Oral calcium salts are predicted to decrease the absorption of

levothyroxine

o

. Separate administration by at least 4 hours.

Anecdotal

▶ Thyroid hormones are predicted to affect the concentration of

digoxin. Monitor and adjust dose.oTheoretical

▶ HIV-protease inhibitors (ritonavir) decrease the concentration of

levothyroxine. MHRA advises monitor TSH for at least one

month after starting or stopping ritonavir.oAnecdotal

▶ Oral hormone replacement therapy is predicted to decrease the

effects of thyroid hormones.oTheoretical

▶ Iron (oral) decreases the absorption of levothyroxine. Separate

administration by at least 4 hours.oStudy

▶ Lanthanum decreases the absorption of thyroid hormones.

Separate administration by 2 hours.oStudy

▶ Paritaprevir (with ritonavir and ombitasvir) is predicted to

increase the exposure to levothyroxine. Monitor and adjust

dose.oTheoretical

▶ Sucralfate decreases the absorption of levothyroxine. Separate

administration by at least 4 hours.oStudy

Tiagabine → see antiepileptics

Tiaprofenic acid → see NSAIDs

Tibolone → see TABLE 5 p. 1375 (thromboembolism)

Ticagrelor → see TABLE 4 p. 1375 (antiplatelet effects)

▶ Antiarrhythmics (amiodarone) are predicted to increase the

exposure to ticagrelor. Use with caution or avoid.rStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to markedly decrease the

exposure to ticagrelor. Avoid.rStudy

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

predicted to markedly increase the exposure to ticagrelor.

Avoid.rStudy

▶ Apalutamide is predicted to decrease the exposure to

ticagrelor. Monitor and adjust dose.oStudy

▶ Bosentan

o

is predicted to decrease the exposure to ticagrelor.

Theoretical

▶ Ciclosporin is predicted to increase the exposure to ticagrelor.

Use with caution or avoid.rStudy

▶ Cobicistat is predicted to markedly increase the exposure to

ticagrelor. Avoid.rStudy

▶ Ticagrelor

Study

increases the concentration of digoxin.o ▶ Efavirenz

o

is predicted to decrease the exposure to ticagrelor.

Theoretical

▶ Enzalutamide is predicted to markedly decrease the exposure

to ticagrelor. Avoid.rStudy

▶ Ticagrelor is predicted to increase the exposure to ergotamine.

Avoid.rTheoretical

▶ Grapefruit juice moderately increases the exposure to

ticagrelor.oStudy

1544 Theophylline —Ticagrelor BNF 78

Interactions | Appendix 1

A1

▶ HIV-protease inhibitors are predicted to markedly increase the

exposure to ticagrelor. Avoid.rStudy

▶ Idelalisib is predicted to markedly increase the exposure to

ticagrelor. Avoid.rStudy

▶ Ticagrelor is predicted to increase the exposure to lomitapide.

Separate administration by 12 hours.oTheoretical

▶ Macrolides (azithromycin) are predicted to increase the

exposure to ticagrelor. Use with caution or avoid.rStudy

▶ Macrolides (clarithromycin) are predicted to markedly increase

the exposure to ticagrelor. Avoid.rStudy

▶ Mitotane is predicted to markedly decrease the exposure to

ticagrelor. Avoid.rStudy

▶ Nevirapine

o

is predicted to decrease the exposure to ticagrelor.

Theoretical

▶ Ranolazine is predicted to increase the exposure to ticagrelor.

Use with caution or avoid.rStudy

▶ Rifampicin is predicted to markedly decrease the exposure to

ticagrelor. Avoid.rStudy

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

ticagrelor.oTheoretical

▶ Ticagrelor slightly increases the exposure to statins

(simvastatin). Adjust simvastatin dose, p. 205.oStudy

▶ Vemurafenib is predicted to increase the exposure to

ticagrelor. Use with caution or avoid.rStudy

Ticarcillin → see penicillins

Tigecycline → see tetracyclines

Tildrakizumab → see monoclonal antibodies

Timolol → see beta blockers, non-selective

Tinidazole

▶ Alcohol (beverage) potentially causes a disulfiram-like

reaction when given with tinidazole. Avoid for 72 hours

stopping treatment.oTheoretical

▶ Tinidazole is predicted to increase the anticoagulant effect of

coumarins. Monitor INR and adjust dose.rTheoretical

Tinzaparin → see low molecular-weight heparins

Tioguanine → see TABLE 15 p. 1378 (myelosuppression)

▶ Live vaccines are predicted to increase the risk of generalised

infection (possibly life-threatening) when given with

tioguanine. Public Health England advises avoid (refer to

Green Book).rTheoretical

Tiotropium → see TABLE 10 p. 1377 (antimuscarinics)

Tipranavir → see HIV-protease inhibitors

Tirofiban → see TABLE 4 p. 1375 (antiplatelet effects)

Tivozanib

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to tivozanib.rStudy

▶ Enzalutamide is predicted to decrease the exposure to

tivozanib.rStudy

▶ Mitotane

r

is predicted to decrease the exposure to tivozanib.

Study

▶ Rifampicin

r

is predicted to decrease the exposure to tivozanib.

Study

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

tivozanib. Avoid.rStudy

▶ Tivozanib is predicted to decrease the exposure to statins

(rosuvastatin).oTheoretical

Tizanidine → see TABLE 6 p. 1376 (bradycardia), TABLE 8 p. 1376

(hypotension), TABLE 9 p. 1377 (QT-interval prolongation), TABLE 11

p. 1377 (CNS depressant effects)

▶ Antiepileptics (fosphenytoin, phenytoin) moderately decrease

the exposure to tizanidine.nStudy

▶ Combined hormonal contraceptives increase the exposure to

tizanidine. Avoid.oStudy

▶ HIV-protease inhibitors (ritonavir) moderately decrease the

exposure to tizanidine.nStudy

▶ Iron chelators (deferasirox) are predicted to increase the

exposure to tizanidine. Avoid.oTheoretical

▶ Leflunomide moderately decreases the exposure to tizanidine.

nStudy

▶ Mexiletine

o

increases the exposure to tizanidine. Avoid.

Study

▶ Obeticholic acid is predicted to increase the exposure to

tizanidine.rTheoretical

▶ Quinolones (ciprofloxacin) increase the exposure to tizanidine.

Avoid.oStudy

▶ Rifampicin moderately decreases the exposure to tizanidine.

nStudy

▶ Rucaparib is predicted to increase the exposure to tizanidine.

Monitor and adjust dose.oStudy

▶ SSRIs (fluvoxamine) very markedly increase the exposure to

tizanidine. Avoid.rStudy

▶ Teriflunomide moderately decreases the exposure to

tizanidine.nStudy

Tobramycin → see aminoglycosides

Tocilizumab → see monoclonal antibodies

Tofacitinib

▶ Antiarrhythmics (dronedarone) given with a potent CYP2C19

inhibitor are predicted to increase the exposure to tofacitinib.

Adjust tofacitinib dose, p. 1105.oStudy

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to tofacitinib. Avoid.rStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

given with a potent CYP2C19 inhibitor are predicted to

increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

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

predicted to increase the exposure to tofacitinib. Adjust

tofacitinib dose, p. 1105.oStudy

▶ Aprepitant given with a potent CYP2C19 inhibitor is predicted

to increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

▶ Bosentan

o

is predicted to decrease the exposure to tofacitinib.

Study

▶ Calcium channel blockers (diltiazem, verapamil) given with a

potent CYP2C19 inhibitor are predicted to increase the

exposure to

o

tofacitinib. Adjust tofacitinib dose, p. 1105.

Study

▶ Ciclosporin

Study

increases the exposure to tofacitinib. Avoid.r

▶ Cobicistat is predicted to increase the exposure to tofacitinib.

Adjust tofacitinib dose, p. 1105.oStudy

▶ Crizotinib given with a potent CYP2C19 inhibitor is predicted

to increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

▶ Efavirenz

o

is predicted to decrease the exposure to tofacitinib.

Study

▶ Enzalutamide is predicted to decrease the exposure to

tofacitinib. Avoid.rStudy

▶ HIV-protease inhibitors are predicted to increase the exposure

to tofacitinib. Adjust tofacitinib dose, p. 1105.oStudy

▶ Idelalisib is predicted to increase the exposure to tofacitinib.

Adjust tofacitinib dose, p. 1105.oStudy

▶ Imatinib given with a potent CYP2C19 inhibitor is predicted to

increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

▶ Live vaccines potentially increase the risk of generalised

infection (possibly life-threatening) when given with

tofacitinib. Avoid.rTheoretical

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to

o

tofacitinib. Adjust tofacitinib dose, p. 1105.

Study

▶ Macrolides (erythromycin) given with a potent CYP2C19

inhibitor are predicted to increase the exposure to tofacitinib.

Adjust tofacitinib dose, p. 1105.oStudy

▶ Mitotane is predicted to decrease the exposure to tofacitinib.

Avoid.rStudy

▶ Netupitant given with a potent CYP2C19 inhibitor is predicted

to increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

▶ Nevirapine

o

is predicted to decrease the exposure to tofacitinib.

Study

▶ Nilotinib given with a potent CYP2C19 inhibitor is predicted to

increase the exposure to tofacitinib. Adjust tofacitinib dose,

p. 1105.oStudy

▶ Rifampicin is predicted to decrease the exposure to tofacitinib.

Avoid.rStudy

BNF 78 Ticagrelor —Tofacitinib 1545

Interactions | Appendix 1

A1

Tofacitinib (continued)

▶ SSRIs (fluoxetine, fluvoxamine) given with a moderate CYP3A4

inhibitor are predicted to increase the exposure to tofacitinib.

Adjust tofacitinib dose, p. 1105.oStudy

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

tofacitinib.oStudy

▶ Tacrolimus

Study

increases the exposure to tofacitinib. Avoid.r

Tolbutamide → see sulfonylureas

Tolcapone

▶ Tolcapone increases the exposure to levodopa. Monitor and

adjust dose.oStudy

▶ Tolcapone is predicted to increase the effects of monoamineoxidase A and B inhibitors, irreversible. Avoid.rTheoretical

▶ Tolcapone is predicted to increase the risk of cardiovascular

o

side-effects when given with sympathomimetics, inotropic.

Theoretical

▶ Tolcapone is predicted to increase the effects of

sympathomimetics, vasoconstrictor (adrenaline/epinephrine,

noradrenaline/norepinephrine).oTheoretical

Tolfenamic acid → see NSAIDs

Tolterodine → see TABLE 9 p. 1377 (QT-interval prolongation), TABLE 10

p. 1377 (antimuscarinics)

▶ Antiarrhythmics (dronedarone) are predicted to increase the

exposure to tolterodine.nTheoretical → Also see TABLE 9

p. 1377

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to tolterodine.n Theoretical → Also see TABLE 9 p. 1377

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

predicted to increase the exposure to

r

tolterodine. Avoid.

Study → Also see TABLE 9 p. 1377

▶ Aprepitant is predicted to increase the exposure to tolterodine.

nTheoretical

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

increase the exposure to tolterodine.nTheoretical

▶ Cobicistat is predicted to increase the exposure to tolterodine.

Avoid.rStudy

▶ Crizotinib is predicted to increase the exposure to tolterodine.

nTheoretical → Also see TABLE 9 p. 1377

▶ Eliglustat is predicted to increase the exposure to tolterodine.

Adjust dose.oTheoretical

▶ HIV-protease inhibitors are predicted to increase the exposure

to tolterodine. Avoid.rStudy → Also see TABLE 9 p. 1377

▶ Idelalisib is predicted to increase the exposure to tolterodine.

Avoid.rStudy

▶ Imatinib is predicted to increase the exposure to tolterodine.

nTheoretical

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to tolterodine. Avoid.rStudy → Also see TABLE 9

p. 1377

▶ Macrolides (erythromycin) are predicted to increase the

exposure to tolterodine.nTheoretical → Also see TABLE 9

p. 1377

▶ Netupitant is predicted to increase the exposure to tolterodine.

nTheoretical

▶ Nilotinib is predicted to increase the exposure to tolterodine.

nTheoretical → Also see TABLE 9 p. 1377

Tolvaptan → see TABLE 16 p. 1379 (increased serum potassium)

GENERAL INFORMATION Avoid concurrent use of drugs that

increase serum-sodium concentrations.

▶ Antiarrhythmics (dronedarone) are predicted to increase the

exposure to tolvaptan. Manufacturer advises caution or adjust

tolvaptan

o

dose with moderate inhibitors of CYP3A4, p. 669.

Study

▶ Antiepileptics (carbamazepine, fosphenytoin, phenobarbital,

phenytoin, primidone) are predicted to decrease the exposure

to tolvaptan. Use with caution or avoid depending on

indication.rStudy

▶ Antifungals, azoles (fluconazole, isavuconazole, posaconazole)

are predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

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

predicted to increase the exposure to tolvaptan. Manufacturer

advises caution or adjust tolvaptan dose with potent inhibitors

of CYP3A4, p. 669.rStudy

▶ Apalutamide is predicted to decrease the exposure to

tolvaptan. Avoid or monitor.oStudy

▶ Aprepitant is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

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

increase the exposure to tolvaptan. Manufacturer advises

caution or adjust tolvaptan dose with moderate inhibitors of

CYP3A4, p. 669.oStudy

▶ Cobicistat is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

potent inhibitors of CYP3A4, p. 669.rStudy

▶ Crizotinib is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

▶ Tolvaptan increases the concentration of digoxin.nStudy

▶ Enzalutamide is predicted to decrease the exposure to

tolvaptan

r

. Use with caution or avoid depending on indication.

Study

▶ Grapefruit juice

o

increases the exposure to tolvaptan. Avoid.

Study

▶ HIV-protease inhibitors are predicted to increase the exposure

to tolvaptan. Manufacturer advises caution or adjust tolvaptan

dose with potent inhibitors of CYP3A4, p. 669.rStudy

▶ Idelalisib is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

potent inhibitors of CYP3A4, p. 669.rStudy

▶ Imatinib is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

▶ Tolvaptan is predicted to increase the exposure to lomitapide.

Separate administration by 12 hours.oTheoretical

▶ Macrolides (clarithromycin) are predicted to increase the

exposure to tolvaptan. Manufacturer advises caution or adjust

tolvaptan

Study

dose with potent inhibitors of CYP3A4, p. 669.r

▶ Macrolides (erythromycin) are predicted to increase the

exposure to tolvaptan. Manufacturer advises caution or adjust

tolvaptan

o

dose with moderate inhibitors of CYP3A4, p. 669.

Study

▶ Mitotane is predicted to decrease the exposure to tolvaptan.

Use with caution or avoid depending on indication.

Study

r

▶ Netupitant is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

▶ Nilotinib is predicted to increase the exposure to tolvaptan.

Manufacturer advises caution or adjust tolvaptan dose with

moderate inhibitors of CYP3A4, p. 669.oStudy

▶ Quinolones (ciprofloxacin) are predicted to increase the

exposure to tolvaptan. Use with caution and adjust tolvaptan

dose, p. 669.oTheoretical

▶ Rifampicin is predicted to decrease the exposure to tolvaptan.

Use with caution or avoid depending on indication.

Study

r

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

tolvaptan. Avoid.oTheoretical

Topiramate → see antiepileptics

Topotecan → see TABLE 15 p. 1378 (myelosuppression)

▶ Antiarrhythmics (amiodarone, dronedarone) are predicted to

increase the exposure to topotecan.rStudy

▶ Antiepileptics (fosphenytoin, phenytoin) increase the clearance

of topotecan.oStudy

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

exposure to topotecan.oTheoretical

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

increase the exposure to topotecan.rStudy

▶ Calcium channel blockers (verapamil) are predicted to increase

the exposure to topotecan.rStudy

▶ Ceritinib

o

is predicted to increase the exposure to topotecan.

Theoretical → Also see TABLE 15 p. 1378

▶ Ciclosporin

r

is predicted to increase the exposure to topotecan.

Study

1546 Tofacitinib —Topotecan BNF 78

Interactions | Appendix 1

A1

▶ Eliglustat is predicted to increase the exposure to topotecan.

Adjust dose.oStudy

▶ HIV-protease inhibitors (lopinavir, ritonavir, saquinavir) are

predicted to increase the exposure to topotecan.rStudy

▶ Lapatinib

r

is predicted to increase the exposure to topotecan.

Study

▶ Leflunomide is predicted to increase the exposure to

topotecan.oStudy → Also see TABLE 15 p. 1378

▶ Live vaccines are predicted to increase the risk of generalised

infection (possibly life-threatening) when given with

topotecan. Public Health England advises avoid (refer to Green

Book).rTheoretical

▶ Macrolides are predicted to increase the exposure to

topotecan.rStudy

▶ Mirabegron is predicted to increase the exposure to topotecan.

nTheoretical

▶ Paritaprevir (with ritonavir and ombitasvir) is predicted to

increase the exposure to topotecan.oStudy

▶ Pibrentasvir (with glecaprevir) is predicted to increase the

exposure to topotecan.oStudy

▶ Pitolisant is predicted to decrease the exposure to topotecan.

nTheoretical

▶ Ranolazine

r

is predicted to increase the exposure to topotecan.

Study

▶ Regorafenib

o

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