Cafergot, Migergot (ergotamine/caffeine) dosing, indications, interactions, adverse effects, and more

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Sections ergotamine/caffeine
Dosing & Uses
Interactions
Adverse Effects
Warnings
Pregnancy
Pharmacology
Administration
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

ergotamine/caffeine

oral tablet (Cafergot)

1mg/100mg

rectal suppository (Migergot)

2mg/100mg

Vascular Headache

Indicated as therapy to abort or prevent vascular headache (eg, migraine, migraine variants, “histaminic cephalalgia”)

Not for chronic daily use

Oral

2 tablets (ergotamine 2 mg/caffeine 200 mg) PO at first sign of attack; may take 1 tablet (ergotamine 1 mg/caffeine 100 mg) q30min prn
Not to exceed 6 tablets/attack
Not to exceed 10 tablets/week

Rectal

Insert 1 suppository rectally at first sign of attack; may repeat once after 1 hr
Not to exceed 2 suppositories/attack
Not to exceed 5 suppositories/week

Short-term prevention

In carefully selected patients, with due consideration of maximum dosage recommendations, administration of the drug at bedtime may be an appropriate short-term preventive measure

Dosage Modifications

Renal or hepatic impairment

Contraindicated

Dosing Considerations

Not effective for other types of headaches; lacks analgesic properties

Safety and efficacy not established

Interaction Checker

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Contraindicated (33)

almotriptan
ergotamine, almotriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
clarithromycin
clarithromycin increases toxicity of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration may result in vasospasm and ischemia of the extremities and other tissues including the CNS.
cobicistat
cobicistat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)
eletriptan
ergotamine, eletriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
fezolinetant
caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
frovatriptan
ergotamine, frovatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
glyceryl trinitrate pr
ergotamine decreases effects of glyceryl trinitrate pr by pharmacodynamic antagonism. Contraindicated.
isocarboxazid
isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
itraconazole
itraconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremities
ketoconazole
ketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
letermovir
letermovir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.
levoketoconazole
levoketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
linezolid
linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
mifepristone
mifepristone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with CYP3A substrates that have a narrow therapeutic index .
naratriptan
ergotamine, naratriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
nirmatrelvir
nirmatrelvir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
nitroglycerin IV
ergotamine decreases effects of nitroglycerin IV by pharmacodynamic antagonism. Contraindicated.
nitroglycerin sublingual
ergotamine decreases effects of nitroglycerin sublingual by pharmacodynamic antagonism. Contraindicated.
nitroglycerin topical
ergotamine decreases effects of nitroglycerin topical by pharmacodynamic antagonism. Contraindicated.
nitroglycerin transdermal
ergotamine decreases effects of nitroglycerin transdermal by pharmacodynamic antagonism. Contraindicated.
nitroglycerin translingual
ergotamine decreases effects of nitroglycerin translingual by pharmacodynamic antagonism. Contraindicated.
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Acute ergot toxicity characterized by vasospasm and tissue ischemia has been associated with coadministration of ritonavir
phenelzine
phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
procarbazine
procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.
pseudoephedrine
ergotamine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.
rizatriptan
ergotamine, rizatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
selegiline transdermal
selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
sumatriptan
ergotamine, sumatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
sumatriptan intranasal
ergotamine, sumatriptan intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.
tranylcypromine
tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.
voriconazole
voriconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

Serious - Use Alternative (122)

abametapir
abametapir will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

abametapir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
amobarbital
amobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
bupropion
caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.
amyl nitrite
amyl nitrite increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
apalutamide
apalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
aprepitant
aprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
armodafinil
armodafinil will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
atazanavir
atazanavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

atazanavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
benzphetamine
ergotamine, benzphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
bosentan
bosentan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
bremelanotide
bremelanotide will decrease the level or effect of ergotamine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
brigatinib
brigatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.
bromocriptine
ergotamine, bromocriptine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. The concomitant use of bromocriptine with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided.
budesonide
budesonide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
butabarbital
butabarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
butalbital
butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
carbamazepine
carbamazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ceritinib
ceritinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose reduction.
cimetidine
cimetidine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
clarithromycin
clarithromycin increases levels of ergotamine by decreasing metabolism. Contraindicated.
conivaptan
conivaptan will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
cortisone
cortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cyclosporine
cyclosporine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
darifenacin
darifenacin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
darunavir
darunavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. "Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. "
dasatinib
dasatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
desvenlafaxine
ergotamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
dexamethasone
dexamethasone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
dexfenfluramine
dexfenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.

ergotamine, dexfenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dexmethylphenidate
ergotamine, dexmethylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dextroamphetamine
ergotamine, dextroamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
DHEA, herbal
DHEA, herbal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
diethylpropion
ergotamine, diethylpropion. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dipyridamole
caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
dobutamine
ergotamine, dobutamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dopamine
ergotamine, dopamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dronedarone
dronedarone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
efavirenz
efavirenz will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

efavirenz increases levels of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.
enzalutamide
enzalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ephedrine
ergotamine, ephedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
epinephrine
ergotamine, epinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
erythromycin base
erythromycin base will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin stearate
erythromycin stearate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
etravirine
etravirine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fenfluramine
fenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.

ergotamine, fenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
fexinidazole
fexinidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
fluconazole
fluconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fludrocortisone
fludrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
fluvoxamine
fluvoxamine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fosamprenavir
fosamprenavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

fosamprenavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
fosaprepitant
fosaprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fosphenytoin
fosphenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
givosiran
givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
glyceryl trinitrate pr
glyceryl trinitrate pr increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
grapefruit
grapefruit will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
griseofulvin
griseofulvin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
hydrocortisone
hydrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
idelalisib
idelalisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
indinavir
indinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

indinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
iobenguane I 131
caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
isocarboxazid
isocarboxazid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
isoniazid
isoniazid will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
isoproterenol
ergotamine, isoproterenol. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
isosorbide dinitrate
isosorbide dinitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
isosorbide mononitrate
isosorbide mononitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
lapatinib
lapatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
lenacapavir
lenacapavir will increase the level or effect of ergotamine by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Coadministration of lenacapavir with dihydroergotamine, ergotamine or methylergonovine is not recommended.

lenacapavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
linezolid
linezolid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
lisdexamfetamine
ergotamine, lisdexamfetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
lonafarnib
ergotamine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
lopinavir
lopinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
lorlatinib
lorlatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.
lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.
lumefantrine
lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
marijuana
marijuana will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
methamphetamine
ergotamine, methamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methylene blue
methylene blue and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
methylenedioxymethamphetamine
ergotamine, methylenedioxymethamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methylphenidate
ergotamine, methylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methylprednisolone
methylprednisolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
metronidazole
metronidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
miconazole vaginal
miconazole vaginal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
midodrine
ergotamine, midodrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
mobocertinib
mobocertinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.
nefazodone
nefazodone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
nelfinavir
nelfinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

nelfinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
nevirapine
nevirapine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
nicorandil
nicorandil increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nifedipine
nifedipine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
nilotinib
nilotinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
nitroglycerin IV
nitroglycerin IV increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin PO
nitroglycerin PO increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin sublingual
nitroglycerin sublingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin topical
nitroglycerin topical increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin transdermal
nitroglycerin transdermal increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin translingual
nitroglycerin translingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
norepinephrine
ergotamine, norepinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
olutasidenib
olutasidenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
oxcarbazepine
oxcarbazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ozanimod
ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
pacritinib
pacritinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
pentobarbital
pentobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
pexidartinib
pexidartinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.
phendimetrazine
ergotamine, phendimetrazine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenelzine
phenelzine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
phenobarbital
phenobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phentermine
ergotamine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenylephrine
ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenylephrine PO
ergotamine, phenylephrine PO. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenytoin
phenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
posaconazole
posaconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
prednisone
prednisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
primidone
primidone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
procarbazine
procarbazine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
propylhexedrine
ergotamine, propylhexedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
regadenoson
caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.
rifabutin
rifabutin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

Monitor Closely (254)

5-HTP
5-HTP and ergotamine both increase serotonin levels. Use Caution/Monitor.
albuterol
albuterol and caffeine both decrease sedation. Use Caution/Monitor.
alfentanil
alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
almotriptan
almotriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
alprazolam
alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
amitriptyline
amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
amobarbital
amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
amoxapine
amoxapine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
amoxapine
amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
arformoterol
arformoterol and caffeine both decrease sedation. Use Caution/Monitor.
aripiprazole
aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
armodafinil
armodafinil and caffeine both decrease sedation. Use Caution/Monitor.
asenapine
ergotamine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
atogepant
ergotamine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
avapritinib
ergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
axitinib
ergotamine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
azelastine
azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
belladonna and opium
belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
belzutifan
belzutifan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
benperidol
benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
benzphetamine
caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.
berotralstat
berotralstat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.
brompheniramine
brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
buprenorphine buccal
buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
buspirone
buspirone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
butabarbital
butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital
butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butorphanol
butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
carbinoxamine
carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cariprazine
ergotamine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
cenobamate
cenobamate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
chloral hydrate
chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlordiazepoxide
chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine
chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpromazine
chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cinnarizine
cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ciprofloxacin
ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.
citalopram
citalopram and ergotamine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
clemastine
clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clomipramine
clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

clomipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
clonazepam
clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clozapine
ergotamine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
clorazepate
clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clozapine
clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cocaine topical
cocaine topical and ergotamine both increase serotonin levels. Use Caution/Monitor.
codeine
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
crizotinib
crizotinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.
crofelemer
crofelemer increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
cyclizine
cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cyproheptadine
cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dabrafenib
dabrafenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
deferasirox
deferasirox will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use ergot alkaloids with caution with less potent CYP3A4 inhibitors.

deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
desipramine
desipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexchlorpheniramine
dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexfenfluramine
dexfenfluramine and ergotamine both increase serotonin levels. Use Caution/Monitor.
dexfenfluramine
caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.
dexmedetomidine
dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexmethylphenidate
caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.
dextroamphetamine
dextroamphetamine and ergotamine both increase serotonin levels. Use Caution/Monitor.

caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.
dextromethorphan
dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
dextromoramide
dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diamorphine
diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diethylpropion
caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.
difenoxin hcl
difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dihydroergotamine
dihydroergotamine and ergotamine both increase serotonin levels. Use Caution/Monitor.
dihydroergotamine intranasal
dihydroergotamine intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.
diltiazem
diltiazem will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
dimenhydrinate
dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diphenhydramine
diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diphenoxylate hcl
diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dipipanone
dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dobutamine
dobutamine and caffeine both decrease sedation. Use Caution/Monitor.
dopamine
caffeine and dopamine both decrease sedation. Use Caution/Monitor.
dopexamine
dopexamine and caffeine both decrease sedation. Use Caution/Monitor.
doxepin
doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

doxepin and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
droperidol
droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
duloxetine
duloxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
droxidopa
caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension
duvelisib
duvelisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
elagolix
elagolix will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered.
eletriptan
eletriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
eluxadoline
eluxadoline increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.
ephedrine
ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
epinephrine
epinephrine and caffeine both decrease sedation. Use Caution/Monitor.
epinephrine inhaled
caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
epinephrine racemic
epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.
escitalopram
escitalopram and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
esketamine intranasal
esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
estazolam
estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ethanol
ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ethinylestradiol
ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
fedratinib
fedratinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
fenfluramine
ergotamine and fenfluramine both increase serotonin levels. Use Caution/Monitor.

ergotamine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.

caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.
ferric maltol
ferric maltol, ergotamine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).
fexinidazole
fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
finerenone
ergotamine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.
flibanserin
ergotamine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
fluoxetine
fluoxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
fluphenazine
fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
flurazepam
flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
fluvoxamine
fluvoxamine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
fluvoxamine
fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
formoterol
formoterol and caffeine both decrease sedation. Use Caution/Monitor.
frovatriptan
frovatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
glycerol phenylbutyrate
glycerol phenylbutyrate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.
green tea
green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.
guselkumab
guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
haloperidol
haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
hydromorphone
hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
iloperidone
iloperidone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

ergotamine, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
hydroxyzine
hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
iloperidone
iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
imipramine
imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

imipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
isavuconazonium sulfate
ergotamine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

isavuconazonium sulfate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
isoproterenol
isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.
isoniazid
ergotamine and isoniazid both increase serotonin levels. Use Caution/Monitor.
istradefylline
istradefylline will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
L-tryptophan
ergotamine and L-tryptophan both increase serotonin levels. Use Caution/Monitor.
ketotifen, ophthalmic
ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
larotrectinib
larotrectinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
lemborexant
ergotamine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
letermovir
letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
levalbuterol
levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.
levomilnacipran
levomilnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
levorphanol
levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
levothyroxine
caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.
lisdexamfetamine
caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.
lithium
ergotamine and lithium both increase serotonin levels. Use Caution/Monitor.
lofepramine
lofepramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lofexidine
lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lomitapide
ergotamine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
loprazolam
loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lorazepam
lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lormetazepam
lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
loxapine
ergotamine, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
loxapine inhaled
loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
lsd
ergotamine and lsd both increase serotonin levels. Use Caution/Monitor.
maprotiline
maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lurasidone
ergotamine, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
maprotiline
maprotiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
marijuana
marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
melatonin
melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
meperidine
ergotamine and meperidine both increase serotonin levels. Modify Therapy/Monitor Closely.

meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
meprobamate
meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
midazolam intranasal
ergotamine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
metaproterenol
metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
methadone
methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
methamphetamine
caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.
methotrexate
caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.
methylenedioxymethamphetamine
caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.
methylphenidate
caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.
midazolam
midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
midodrine
caffeine and midodrine both decrease sedation. Use Caution/Monitor.
milnacipran
milnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
minocycline
minocycline, ergotamine. Either increases toxicity of the other by Mechanism: unknown. Use Caution/Monitor. coadministration of ergot alkaloids and tetracyclines increases risk of ergotism.
mirtazapine
ergotamine and mirtazapine both increase serotonin levels. Use Caution/Monitor.

mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
mitotane
mitotane decreases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
modafinil
caffeine and modafinil both decrease sedation. Use Caution/Monitor.
molindone
ergotamine, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
morphine
ergotamine and morphine both increase serotonin levels. Use Caution/Monitor.

morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
motherwort
motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
naratriptan
naratriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
moxonidine
moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
nabilone
nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
nalbuphine
nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
nefazodone
nefazodone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
nitroglycerin rectal
nitroglycerin rectal will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and consequently increases its oral bioavailability. Ergotamine is known to precipitate angina pectoris. Therefore the possibility of ergotism in patients receiving nitroglycerin should be considered.
norepinephrine
norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
nortriptyline
nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

nortriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
olanzapine
olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
omaveloxolone
omaveloxolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.
opium tincture
opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxazepam
oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxycodone
oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxymorphone
oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
palbociclib
palbociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib
paliperidone
ergotamine, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
papaveretum
papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
paroxetine
paroxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
pefloxacin
pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
pentazocine
pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine and pentazocine both increase serotonin levels. Use Caution/Monitor.
pentobarbital
pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
perphenazine
ergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
perphenazine
perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
phendimetrazine
caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.
phenobarbital
phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
phentermine
caffeine and phentermine both decrease sedation. Use Caution/Monitor.
phenylephrine
caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.
phenylephrine PO
caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
pholcodine
pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pimavanserin
ergotamine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
pimozide
ergotamine, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pirbuterol
pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.
pitolisant
pitolisant will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.
primidone
primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
prochlorperazine
prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine
promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
propylhexedrine
caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.
protriptyline
protriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
quazepam
quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
quetiapine
ergotamine, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
quetiapine
quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
rasagiline
rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

rasagiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
ribociclib
ribociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.
risperidone
risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
risperidone
ergotamine, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
rizatriptan
rizatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
ropeginterferon alfa 2b
ropeginterferon alfa 2b will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.
rucaparib
rucaparib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.
SAMe
ergotamine and SAMe both increase serotonin levels. Use Caution/Monitor.
salmeterol
salmeterol and caffeine both decrease sedation. Use Caution/Monitor.
schisandra
schisandra will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
scullcap
scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
secobarbital
secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
selegiline
selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

selegiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
selegiline transdermal
selegiline transdermal and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
shepherd's purse
shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
sertraline
sertraline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
sofosbuvir/velpatasvir
sofosbuvir/velpatasvir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.
St John's Wort
ergotamine and St John's Wort both increase serotonin levels. Modify Therapy/Monitor Closely.
solriamfetol
caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
stiripentol
stiripentol, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.
sufentanil
sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
sumatriptan
sumatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
sumatriptan intranasal
sumatriptan intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.
tapentadol
tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
tazemetostat
tazemetostat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

ergotamine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
teclistamab
teclistamab will increase the level or effect of ergotamine by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.
tecovirimat
tecovirimat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
telotristat ethyl
telotristat ethyl will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
temazepam
temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
terbutaline
terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
teriflunomide
teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
thioridazine
thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
thiothixene
ergotamine, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
tinidazole
ergotamine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
topiramate
topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
tramadol
ergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trazodone
trazodone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
triazolam
triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trifluoperazine
ergotamine, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
triclofos
triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trifluoperazine
trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trimipramine
trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

trimipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
triprolidine
triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trofinetide
trofinetide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
turmeric
turmeric will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ustekinumab
ustekinumab, ergotamine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
venlafaxine
venlafaxine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
xylometazoline
caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.
yohimbine
caffeine and yohimbine both decrease sedation. Use Caution/Monitor.
ziconotide
ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ziprasidone
ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
zolmitriptan
zolmitriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

Minor (46)

acetazolamide
acetazolamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
adenosine
caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.
amantadine
amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.
American ginseng
American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
amobarbital
amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
anastrozole
anastrozole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
armodafinil
armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
azithromycin
azithromycin increases levels of ergotamine by unknown mechanism. Minor/Significance Unknown.
butabarbital
butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
butalbital
butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
calcium acetate
caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.
calcium carbonate
caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.
calcium chloride
caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.
calcium citrate
caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.
calcium gluconate
caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.
carbamazepine
carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
cigarette smoking
cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
cimetidine
cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
clotrimazole
clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
cyclophosphamide
cyclophosphamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
erythromycin base
erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
erythromycin stearate
erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
eucalyptus
eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
fluconazole
fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
grapefruit
grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
green tea
green tea increases levels of ergotamine by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Due to caffeine content.
guarana
guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
isoniazid
isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
itraconazole
itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
ketoconazole
ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
levoketoconazole
levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
mexiletine
mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
miconazole vaginal
miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
modafinil
modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
peginterferon alfa 2a
peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
pentobarbital
pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
phenobarbital
phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
pipemidic acid
pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
posaconazole
posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
primidone
primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
rifampin
rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
ruxolitinib
ergotamine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
ruxolitinib topical
ergotamine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
sage
sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

5-HTP
Monitor Closely (1)5-HTP and ergotamine both increase serotonin levels. Use Caution/Monitor.
abametapir
Serious - Use Alternative (2)abametapir will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

abametapir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
acetazolamide
Minor (1)acetazolamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
adenosine
Minor (1)caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.
albuterol
Monitor Closely (1)albuterol and caffeine both decrease sedation. Use Caution/Monitor.
alfentanil
Monitor Closely (1)alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
almotriptan
Contraindicated (1)ergotamine, almotriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)almotriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
alprazolam
Monitor Closely (1)alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
amantadine
Minor (1)amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.
American ginseng
Minor (1)American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
amitriptyline
Monitor Closely (2)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
amobarbital
Monitor Closely (1)amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)amobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
amoxapine
Monitor Closely (2)amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

amoxapine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
amyl nitrite
Serious - Use Alternative (1)amyl nitrite increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
anastrozole
Minor (1)anastrozole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
apalutamide
Serious - Use Alternative (1)apalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
aprepitant
Serious - Use Alternative (1)aprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
arformoterol
Monitor Closely (1)arformoterol and caffeine both decrease sedation. Use Caution/Monitor.
aripiprazole
Monitor Closely (2)aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
armodafinil
Monitor Closely (1)armodafinil and caffeine both decrease sedation. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)armodafinil will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
artemether/lumefantrine
Serious - Use Alternative (1)artemether/lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
asenapine
Monitor Closely (1)ergotamine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
atazanavir
Serious - Use Alternative (2)atazanavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

atazanavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
atogepant
Monitor Closely (1)ergotamine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
avapritinib
Monitor Closely (1)ergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
axitinib
Monitor Closely (1)ergotamine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
azelastine
Monitor Closely (1)azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
azithromycin
Minor (1)azithromycin increases levels of ergotamine by unknown mechanism. Minor/Significance Unknown.
belladonna and opium
Monitor Closely (1)belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
belzutifan
Monitor Closely (1)belzutifan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
benperidol
Monitor Closely (1)benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
benzphetamine
Monitor Closely (1)caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, benzphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
berotralstat
Monitor Closely (1)berotralstat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.
bosentan
Serious - Use Alternative (1)bosentan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
bremelanotide
Serious - Use Alternative (1)bremelanotide will decrease the level or effect of ergotamine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
brigatinib
Serious - Use Alternative (1)brigatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.
bromocriptine
Serious - Use Alternative (1)ergotamine, bromocriptine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. The concomitant use of bromocriptine with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided.
brompheniramine
Monitor Closely (1)brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
budesonide
Serious - Use Alternative (1)budesonide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
buprenorphine buccal
Monitor Closely (1)buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
bupropion
Serious - Use Alternative (1)caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.
buspirone
Monitor Closely (1)buspirone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
butabarbital
Monitor Closely (1)butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)butabarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
butalbital
Monitor Closely (1)butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
butorphanol
Monitor Closely (1)butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
calcium acetate
Minor (1)caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.
calcium carbonate
Minor (1)caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.
calcium chloride
Minor (1)caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.
calcium citrate
Minor (1)caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.
calcium gluconate
Minor (1)caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.
carbamazepine
Minor (1)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)carbamazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
carbinoxamine
Monitor Closely (1)carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cariprazine
Monitor Closely (1)ergotamine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
cenobamate
Monitor Closely (1)cenobamate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
ceritinib
Serious - Use Alternative (1)ceritinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose reduction.
chloral hydrate
Monitor Closely (1)chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlordiazepoxide
Monitor Closely (1)chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpheniramine
Monitor Closely (1)chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
chlorpromazine
Monitor Closely (1)chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cigarette smoking
Minor (1)cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
cimetidine
Minor (1)cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)cimetidine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cinnarizine
Monitor Closely (1)cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ciprofloxacin
Monitor Closely (1)ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.
citalopram
Monitor Closely (1)citalopram and ergotamine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
clarithromycin
Contraindicated (1)clarithromycin increases toxicity of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration may result in vasospasm and ischemia of the extremities and other tissues including the CNS.Serious - Use Alternative (1)clarithromycin increases levels of ergotamine by decreasing metabolism. Contraindicated.
clemastine
Monitor Closely (1)clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clomipramine
Monitor Closely (2)clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

clomipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
clonazepam
Monitor Closely (1)clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clorazepate
Monitor Closely (1)clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clotrimazole
Minor (1)clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
clozapine
Monitor Closely (2)clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
cobicistat
Contraindicated (1)cobicistat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)
cocaine topical
Monitor Closely (1)cocaine topical and ergotamine both increase serotonin levels. Use Caution/Monitor.
codeine
Monitor Closely (1)codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
conivaptan
Serious - Use Alternative (1)conivaptan will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
cortisone
Serious - Use Alternative (1)cortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
crizotinib
Monitor Closely (1)crizotinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.
crofelemer
Monitor Closely (1)crofelemer increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
cyclizine
Monitor Closely (1)cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cyclophosphamide
Minor (1)cyclophosphamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
cyclosporine
Serious - Use Alternative (1)cyclosporine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
cyproheptadine
Monitor Closely (1)cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dabrafenib
Monitor Closely (1)dabrafenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
darifenacin
Serious - Use Alternative (1)darifenacin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
darunavir
Serious - Use Alternative (1)darunavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. "Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. "
dasatinib
Serious - Use Alternative (1)dasatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
deferasirox
Monitor Closely (2)deferasirox will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use ergot alkaloids with caution with less potent CYP3A4 inhibitors.

deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
desipramine
Monitor Closely (2)desipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
desvenlafaxine
Serious - Use Alternative (1)ergotamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
dexamethasone
Serious - Use Alternative (1)dexamethasone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
dexchlorpheniramine
Monitor Closely (1)dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexfenfluramine
Monitor Closely (2)caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

dexfenfluramine and ergotamine both increase serotonin levels. Use Caution/Monitor.Serious - Use Alternative (2)dexfenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.

ergotamine, dexfenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dexmedetomidine
Monitor Closely (1)dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexmethylphenidate
Monitor Closely (1)caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dexmethylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dextroamphetamine
Monitor Closely (2)dextroamphetamine and ergotamine both increase serotonin levels. Use Caution/Monitor.

caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dextroamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dextromethorphan
Monitor Closely (1)dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
dextromoramide
Monitor Closely (1)dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
DHEA, herbal
Serious - Use Alternative (1)DHEA, herbal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
diamorphine
Monitor Closely (1)diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diethylpropion
Monitor Closely (1)caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, diethylpropion. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
difenoxin hcl
Monitor Closely (1)difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dihydroergotamine
Monitor Closely (1)dihydroergotamine and ergotamine both increase serotonin levels. Use Caution/Monitor.
dihydroergotamine intranasal
Monitor Closely (1)dihydroergotamine intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.
diltiazem
Monitor Closely (1)diltiazem will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
dimenhydrinate
Monitor Closely (1)dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diphenhydramine
Monitor Closely (1)diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
diphenoxylate hcl
Monitor Closely (1)diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dipipanone
Monitor Closely (1)dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dipyridamole
Serious - Use Alternative (1)caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
dobutamine
Monitor Closely (1)dobutamine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dobutamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dopamine
Monitor Closely (1)caffeine and dopamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dopamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
dopexamine
Monitor Closely (1)dopexamine and caffeine both decrease sedation. Use Caution/Monitor.
doxepin
Monitor Closely (2)doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

doxepin and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
dronedarone
Serious - Use Alternative (1)dronedarone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
droperidol
Monitor Closely (1)droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
droxidopa
Monitor Closely (1)caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension
duloxetine
Monitor Closely (1)duloxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
duvelisib
Monitor Closely (1)duvelisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
efavirenz
Serious - Use Alternative (2)efavirenz will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

efavirenz increases levels of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.
elagolix
Monitor Closely (1)elagolix will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered.
eletriptan
Contraindicated (1)ergotamine, eletriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)eletriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
eluxadoline
Monitor Closely (1)eluxadoline increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.
elvitegravir/cobicistat/emtricitabine/tenofovir DF
Contraindicated (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
enzalutamide
Serious - Use Alternative (1)enzalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ephedrine
Monitor Closely (1)ephedrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, ephedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
epinephrine
Monitor Closely (1)epinephrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, epinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
epinephrine inhaled
Monitor Closely (1)caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
epinephrine racemic
Monitor Closely (1)epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.
erythromycin base
Minor (1)erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)erythromycin base will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin ethylsuccinate
Minor (1)erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin lactobionate
Minor (1)erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
erythromycin stearate
Minor (1)erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
escitalopram
Monitor Closely (1)escitalopram and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
esketamine intranasal
Monitor Closely (1)esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
eslicarbazepine acetate
Serious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
estazolam
Monitor Closely (1)estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ethanol
Monitor Closely (1)ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ethinylestradiol
Monitor Closely (1)ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
etravirine
Serious - Use Alternative (1)etravirine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
eucalyptus
Minor (1)eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
fedratinib
Monitor Closely (1)fedratinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
fenfluramine
Monitor Closely (3)ergotamine and fenfluramine both increase serotonin levels. Use Caution/Monitor.

caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.

ergotamine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.Serious - Use Alternative (2)fenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.

ergotamine, fenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
ferric maltol
Monitor Closely (1)ferric maltol, ergotamine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).
fexinidazole
Monitor Closely (1)fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fexinidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
fezolinetant
Contraindicated (1)caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
finerenone
Monitor Closely (1)ergotamine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.
flibanserin
Monitor Closely (1)ergotamine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
fluconazole
Minor (1)fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)fluconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fludrocortisone
Serious - Use Alternative (1)fludrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
fluoxetine
Monitor Closely (1)fluoxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
fluphenazine
Monitor Closely (2)fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
flurazepam
Monitor Closely (1)flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
fluvoxamine
Monitor Closely (2)fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

fluvoxamine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
formoterol
Monitor Closely (1)formoterol and caffeine both decrease sedation. Use Caution/Monitor.
fosamprenavir
Serious - Use Alternative (2)fosamprenavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

fosamprenavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
fosaprepitant
Serious - Use Alternative (1)fosaprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
fosphenytoin
Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
frovatriptan
Contraindicated (1)ergotamine, frovatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)frovatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
givosiran
Serious - Use Alternative (1)givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
glycerol phenylbutyrate
Monitor Closely (1)glycerol phenylbutyrate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.
glyceryl trinitrate pr
Contraindicated (1)ergotamine decreases effects of glyceryl trinitrate pr by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)glyceryl trinitrate pr increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
grapefruit
Minor (1)grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)grapefruit will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
green tea
Monitor Closely (1)green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.Minor (1)green tea increases levels of ergotamine by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Due to caffeine content.
griseofulvin
Serious - Use Alternative (1)griseofulvin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
guarana
Minor (1)guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
guselkumab
Monitor Closely (1)guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
haloperidol
Monitor Closely (2)haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
hydrocortisone
Serious - Use Alternative (1)hydrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
hydromorphone
Monitor Closely (1)hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
hydroxyzine
Monitor Closely (1)hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
idelalisib
Serious - Use Alternative (1)idelalisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
iloperidone
Monitor Closely (3)iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

iloperidone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
imipramine
Monitor Closely (2)imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

imipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
indinavir
Serious - Use Alternative (2)indinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

indinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
iobenguane I 131
Serious - Use Alternative (1)caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
isavuconazonium sulfate
Monitor Closely (2)ergotamine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

isavuconazonium sulfate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
isocarboxazid
Contraindicated (1)isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)isocarboxazid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
isoniazid
Monitor Closely (1)ergotamine and isoniazid both increase serotonin levels. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)isoniazid will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
isoproterenol
Monitor Closely (1)isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, isoproterenol. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
isosorbide dinitrate
Serious - Use Alternative (1)isosorbide dinitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
isosorbide mononitrate
Serious - Use Alternative (1)isosorbide mononitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
istradefylline
Monitor Closely (1)istradefylline will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
itraconazole
Contraindicated (1)itraconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremitiesMinor (1)itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
ketoconazole
Contraindicated (1)ketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
ketotifen, ophthalmic
Monitor Closely (1)ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
L-tryptophan
Monitor Closely (1)ergotamine and L-tryptophan both increase serotonin levels. Use Caution/Monitor.
lapatinib
Serious - Use Alternative (1)lapatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
larotrectinib
Monitor Closely (1)larotrectinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
lemborexant
Monitor Closely (1)ergotamine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
lenacapavir
Serious - Use Alternative (2)lenacapavir will increase the level or effect of ergotamine by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Coadministration of lenacapavir with dihydroergotamine, ergotamine or methylergonovine is not recommended.

lenacapavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
letermovir
Contraindicated (1)letermovir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.Monitor Closely (1)letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
levalbuterol
Monitor Closely (1)levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.
levoketoconazole
Contraindicated (1)levoketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
levomilnacipran
Monitor Closely (1)levomilnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
levorphanol
Monitor Closely (1)levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
levothyroxine
Monitor Closely (1)caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.
linezolid
Contraindicated (1)linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)linezolid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
lisdexamfetamine
Monitor Closely (1)caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, lisdexamfetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
lithium
Monitor Closely (1)ergotamine and lithium both increase serotonin levels. Use Caution/Monitor.
lofepramine
Monitor Closely (2)lofepramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lofexidine
Monitor Closely (1)lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lomitapide
Monitor Closely (1)ergotamine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
lonafarnib
Serious - Use Alternative (1)ergotamine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
lopinavir
Serious - Use Alternative (1)lopinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
loprazolam
Monitor Closely (1)loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lorazepam
Monitor Closely (1)lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lorlatinib
Serious - Use Alternative (1)lorlatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.
lormetazepam
Monitor Closely (1)lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
loxapine
Monitor Closely (2)ergotamine, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
loxapine inhaled
Monitor Closely (2)loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
lsd
Monitor Closely (1)ergotamine and lsd both increase serotonin levels. Use Caution/Monitor.
lumacaftor/ivacaftor
Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.
lumefantrine
Serious - Use Alternative (1)lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
lurasidone
Monitor Closely (1)ergotamine, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
maprotiline
Monitor Closely (2)maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

maprotiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
marijuana
Monitor Closely (1)marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)marijuana will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
melatonin
Monitor Closely (1)melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
meperidine
Monitor Closely (2)ergotamine and meperidine both increase serotonin levels. Modify Therapy/Monitor Closely.

meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
meprobamate
Monitor Closely (1)meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
metaproterenol
Monitor Closely (1)metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
methadone
Monitor Closely (1)methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
methamphetamine
Monitor Closely (1)caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, methamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methotrexate
Monitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.
methylene blue
Serious - Use Alternative (1)methylene blue and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
methylenedioxymethamphetamine
Monitor Closely (1)caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, methylenedioxymethamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methylphenidate
Monitor Closely (1)caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.Serious - Use Alternative (1)ergotamine, methylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
methylprednisolone
Serious - Use Alternative (1)methylprednisolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
metronidazole
Serious - Use Alternative (1)metronidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
mexiletine
Minor (1)mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
miconazole vaginal
Minor (1)miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)miconazole vaginal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
midazolam
Monitor Closely (1)midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
midazolam intranasal
Monitor Closely (1)ergotamine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
midodrine
Monitor Closely (1)caffeine and midodrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, midodrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
mifepristone
Contraindicated (1)mifepristone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with CYP3A substrates that have a narrow therapeutic index .
milnacipran
Monitor Closely (1)milnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
minocycline
Monitor Closely (1)minocycline, ergotamine. Either increases toxicity of the other by Mechanism: unknown. Use Caution/Monitor. coadministration of ergot alkaloids and tetracyclines increases risk of ergotism.
mirtazapine
Monitor Closely (2)ergotamine and mirtazapine both increase serotonin levels. Use Caution/Monitor.

mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
mitotane
Monitor Closely (1)mitotane decreases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
mobocertinib
Serious - Use Alternative (1)mobocertinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.
modafinil
Monitor Closely (1)caffeine and modafinil both decrease sedation. Use Caution/Monitor.Minor (1)modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
molindone
Monitor Closely (1)ergotamine, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
morphine
Monitor Closely (2)morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine and morphine both increase serotonin levels. Use Caution/Monitor.
motherwort
Monitor Closely (1)motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
moxonidine
Monitor Closely (1)moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
nabilone
Monitor Closely (1)nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
nalbuphine
Monitor Closely (1)nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
naratriptan
Contraindicated (1)ergotamine, naratriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)naratriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
nefazodone
Monitor Closely (1)nefazodone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)nefazodone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
nelfinavir
Serious - Use Alternative (2)nelfinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

nelfinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
nevirapine
Serious - Use Alternative (1)nevirapine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
nicorandil
Serious - Use Alternative (1)nicorandil increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nifedipine
Serious - Use Alternative (1)nifedipine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
nilotinib
Serious - Use Alternative (1)nilotinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
nirmatrelvir
Contraindicated (1)nirmatrelvir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
nirmatrelvir/ritonavir
Contraindicated (1)nirmatrelvir/ritonavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.
nitroglycerin IV
Contraindicated (1)ergotamine decreases effects of nitroglycerin IV by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin IV increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin PO
Serious - Use Alternative (1)nitroglycerin PO increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin rectal
Monitor Closely (1)nitroglycerin rectal will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and consequently increases its oral bioavailability. Ergotamine is known to precipitate angina pectoris. Therefore the possibility of ergotism in patients receiving nitroglycerin should be considered.
nitroglycerin sublingual
Contraindicated (1)ergotamine decreases effects of nitroglycerin sublingual by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin sublingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin topical
Contraindicated (1)ergotamine decreases effects of nitroglycerin topical by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin topical increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin transdermal
Contraindicated (1)ergotamine decreases effects of nitroglycerin transdermal by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin transdermal increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
nitroglycerin translingual
Contraindicated (1)ergotamine decreases effects of nitroglycerin translingual by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin translingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.
norepinephrine
Monitor Closely (1)norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, norepinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
nortriptyline
Monitor Closely (2)nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

nortriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
olanzapine
Monitor Closely (2)olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
olutasidenib
Serious - Use Alternative (1)olutasidenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.
omaveloxolone
Monitor Closely (1)omaveloxolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
Contraindicated (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Acute ergot toxicity characterized by vasospasm and tissue ischemia has been associated with coadministration of ritonavir
opium tincture
Monitor Closely (1)opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxazepam
Monitor Closely (1)oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxcarbazepine
Serious - Use Alternative (1)oxcarbazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
oxycodone
Monitor Closely (1)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
oxymorphone
Monitor Closely (1)oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
ozanimod
Serious - Use Alternative (1)ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
pacritinib
Serious - Use Alternative (1)pacritinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
palbociclib
Monitor Closely (1)palbociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib
paliperidone
Monitor Closely (2)paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
papaveretum
Monitor Closely (1)papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
paroxetine
Monitor Closely (1)paroxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
pefloxacin
Monitor Closely (1)pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
peginterferon alfa 2a
Minor (1)peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
pentazocine
Monitor Closely (2)pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine and pentazocine both increase serotonin levels. Use Caution/Monitor.
pentobarbital
Monitor Closely (1)pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)pentobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
perphenazine
Monitor Closely (2)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
pexidartinib
Serious - Use Alternative (1)pexidartinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.
phendimetrazine
Monitor Closely (1)caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phendimetrazine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenelzine
Contraindicated (1)phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)phenelzine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
phenobarbital
Monitor Closely (1)phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phentermine
Monitor Closely (1)caffeine and phentermine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenylephrine
Monitor Closely (1)caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenylephrine PO
Monitor Closely (1)caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phenylephrine PO. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
phenytoin
Serious - Use Alternative (1)phenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
pholcodine
Monitor Closely (1)pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pimavanserin
Monitor Closely (1)ergotamine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
pimozide
Monitor Closely (2)ergotamine, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pipemidic acid
Minor (1)pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
pirbuterol
Monitor Closely (1)pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.
pitolisant
Monitor Closely (1)pitolisant will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.
posaconazole
Minor (1)posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)posaconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
prednisone
Serious - Use Alternative (1)prednisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
primidone
Monitor Closely (1)primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)primidone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
procarbazine
Contraindicated (1)procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.Serious - Use Alternative (1)procarbazine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
prochlorperazine
Monitor Closely (1)prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine
Monitor Closely (1)promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
propylhexedrine
Monitor Closely (1)caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, propylhexedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
protriptyline
Monitor Closely (2)protriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pseudoephedrine
Contraindicated (1)ergotamine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.
quazepam
Monitor Closely (1)quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
quetiapine
Monitor Closely (2)quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
quinupristin/dalfopristin
Serious - Use Alternative (1)quinupristin/dalfopristin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rasagiline
Monitor Closely (2)rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

rasagiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
regadenoson
Serious - Use Alternative (1)caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.
ribociclib
Monitor Closely (1)ribociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.
rifabutin
Serious - Use Alternative (1)rifabutin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rifampin
Minor (1)rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)rifampin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
rifapentine
Serious - Use Alternative (1)rifapentine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
risperidone
Monitor Closely (2)risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
ritonavir
Serious - Use Alternative (2)ritonavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

ritonavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
rizatriptan
Contraindicated (1)ergotamine, rizatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)rizatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
ropeginterferon alfa 2b
Monitor Closely (1)ropeginterferon alfa 2b will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.
rucaparib
Monitor Closely (2)rucaparib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.
rufinamide
Serious - Use Alternative (1)rufinamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ruxolitinib
Minor (1)ergotamine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
ruxolitinib topical
Minor (1)ergotamine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
sage
Minor (1)sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
salmeterol
Monitor Closely (1)salmeterol and caffeine both decrease sedation. Use Caution/Monitor.
SAMe
Monitor Closely (1)ergotamine and SAMe both increase serotonin levels. Use Caution/Monitor.
saquinavir
Serious - Use Alternative (2)saquinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

saquinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
schisandra
Monitor Closely (1)schisandra will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
scullcap
Monitor Closely (1)scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
secobarbital
Monitor Closely (1)secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)secobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
selegiline
Monitor Closely (2)selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

selegiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
selegiline transdermal
Contraindicated (1)selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Monitor Closely (1)selegiline transdermal and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
serdexmethylphenidate/dexmethylphenidate
Serious - Use Alternative (1)ergotamine, serdexmethylphenidate/dexmethylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
sertraline
Monitor Closely (1)sertraline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
shepherd's purse
Monitor Closely (1)shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
smoking
Minor (1)smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
sofosbuvir/velpatasvir
Monitor Closely (1)sofosbuvir/velpatasvir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.
solriamfetol
Monitor Closely (1)caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
sotorasib
Serious - Use Alternative (1)sotorasib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications
St John's Wort
Monitor Closely (1)ergotamine and St John's Wort both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
stiripentol
Monitor Closely (2)stiripentol, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.
sufentanil
Monitor Closely (1)sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
sumatriptan
Contraindicated (1)ergotamine, sumatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)sumatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.
sumatriptan intranasal
Contraindicated (1)ergotamine, sumatriptan intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)sumatriptan intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.
tapentadol
Monitor Closely (1)tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
tazemetostat
Monitor Closely (2)tazemetostat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

ergotamine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
teclistamab
Monitor Closely (1)teclistamab will increase the level or effect of ergotamine by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.
tecovirimat
Monitor Closely (1)tecovirimat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
telotristat ethyl
Monitor Closely (1)telotristat ethyl will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.
temazepam
Monitor Closely (1)temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
terbutaline
Monitor Closely (1)terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
teriflunomide
Monitor Closely (1)teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
thiamine
Minor (1)caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.
thioridazine
Monitor Closely (1)thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
thiothixene
Monitor Closely (2)ergotamine, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
tinidazole
Monitor Closely (1)ergotamine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
tipranavir
Serious - Use Alternative (2)tipranavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

tipranavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
tobacco use
Minor (1)tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
topiramate
Monitor Closely (1)topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)topiramate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
tramadol
Monitor Closely (2)ergotamine and tramadol both increase serotonin levels. Use Caution/Monitor.

tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
tranylcypromine
Contraindicated (1)tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)tranylcypromine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.
trazodone
Monitor Closely (2)trazodone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
triamcinolone acetonide injectable suspension
Serious - Use Alternative (1)triamcinolone acetonide injectable suspension will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
triazolam
Monitor Closely (1)triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
triclofos
Monitor Closely (1)triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trifluoperazine
Monitor Closely (2)ergotamine, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

trifluoperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trimipramine
Monitor Closely (2)trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

trimipramine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
triprolidine
Monitor Closely (1)triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
trofinetide
Monitor Closely (1)trofinetide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).
tucatinib
Serious - Use Alternative (1)tucatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
turmeric
Monitor Closely (1)turmeric will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ustekinumab
Monitor Closely (1)ustekinumab, ergotamine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
venlafaxine
Monitor Closely (1)venlafaxine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
verapamil
Minor (1)verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)verapamil will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
voriconazole
Contraindicated (1)voriconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
voxelotor
Serious - Use Alternative (1)voxelotor will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
xylometazoline
Monitor Closely (1)caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, xylometazoline. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
yerba mate
Minor (1)yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
yohimbine
Monitor Closely (1)caffeine and yohimbine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, yohimbine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.
zafirlukast
Serious - Use Alternative (1)zafirlukast will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ziconotide
Monitor Closely (1)ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
zileuton
Minor (1)zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
ziprasidone
Monitor Closely (2)ziprasidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

ergotamine, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
zolmitriptan
Contraindicated (1)ergotamine, zolmitriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)zolmitriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

Frequency Not Defined

Gastrointestinal: Nausea and vomiting; rectal or anal ulcer (from overuse of suppositories)

Neurological: Paresthesia, numbness, weakness, and vertigo

Allergic: Localized edema and itching

Cardiovascular

Serious vasoconstrictive complications may occur including ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes, and muscle pains
Most commonly occurs with long-term therapy at relatively high doses; also reported with short-term or normal doses
Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension

Black Box Warnings

Serious and/or life-threatening peripheral ischemia associated with coadministration of ergotamine and caffeine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics

Because CYP3A4 inhibition elevates ergotamine and caffeine serum levels, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased

Concomitant use of these medications is contraindicated

Contraindications

Potent CYP3A4 inhibitors owing to risk of acute ergot toxicity

Pregnancy

Peripheral vascular disease, coronary heart disease, hypertension, impaired hepatic or renal function, sepsis

Hypersensitivity to any of the ingredients

Cautions

Ergotism

Although ergotism rarely develop even after long-term intermittent use of orally administered ergotamine, do not exceed dosage recommendations
Ergotism manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia
Headache, intermittent claudication, muscle pains, numbness, or coldness and pallor of the digits may occur with chronic intoxication; if the condition is allowed to progress untreated, gangrene can result
While most cases result from frank overdosage, some cases involve hypersensitivity
There are few reports among patients taking doses within recommended limits or for brief periods
Withdrawal symptoms (eg, rebound headache) upon discontinuation are rare; typically reported with long, indiscriminate use

Fibrotic complications

Retroperitoneal and/or pleuropulmonary fibrosis reported
Rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term, continuous use of ergotamine tartrate and caffeine
Do not use for chronic daily administration

Drug interaction overview

Ergotamine is a CYP3A substrate and inhibitor
CYP3A inhibitors
- Potent inhibitors: Contraindicated owing to risk for acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities
- Less potent inhibitors: Although not contraindicated, avoid if possible owing to risk for vasospasm

Pregnancy

Contraindicated; ergotamine elicits oxytocic effects

There are no studies on placental transfer or teratogenicity of the combination of ergotamine and caffeine

Labor and delivery

Contraindicated in labor and delivery owing to ergotamine’s oxytocic effect, which is maximal in the third trimester

Animal studies

Caffeine is known to cross the placenta and has been shown to be teratogenic in animals
Ergotamine crosses the placenta in small amounts, although it does not appear to be embryotoxic in this quantity; however, prolonged vasoconstriction of uterine vessels and/or increased myometrial tone leading to reduced myometrial and placental blood flow may have contributed to fetal growth retardation observed in animals

Lactation

Ergot drugs are known to inhibit prolactin, but there are no reports of decreased lactation with ergotamine/caffeine

Ergotamine is excreted in breast milk and may cause symptoms of vomiting, diarrhea, weak pulse, and unstable blood pressure in nursing infants

Owing to the potential serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Ergotamine: Alpha-adrenergic blocking agent with direct stimulating effect on smooth muscle of peripheral and cranial blood vessels; also elicits serotonin antagonism

Caffeine: Cranial vasoconstrictor; added to further enhance vasoconstrictive effect without increasing ergotamine dosage

Absorption

Bioavailability: <5%

Peak plasma time: 2 hr (PO)

Distribution

Vd: 1.85 L/kg

Metabolism

Extensively metabolized in liver hepatic metabolism

Elimination

Half-life: 2-2.5 hr

Excretion: Feces (90%, mostly as metabolites)

Oral Administration

May take with or without food

Rectal Administration

Remove suppository from foil wrap

Lay on side and insert pointed end of suppository into rectum; remain on side to allow suppository to dissolve and absorb

Avoid handling unwrapped suppository for too long

If needed, may cut suppository lengthwise

Storage

Tablets

Store at 20-25ºC (68-77ºF)
Dispense in tight, light-resistant container

Suppositories

Refrigerate at 2-8ºC (36-46ºF) in sealed foil

Images

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Patient Handout

A Patient Handout is not currently available for this monograph.

Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

View explanations for tiers and restrictions

Tier	Description
1	This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2	This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6	This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC	NOT COVERED – Drugs that are not covered by the plan.

Code	Definition
PA	Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL	Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST	Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR	Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.

Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.

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Sections ergotamine/caffeine
Dosing & Uses
Interactions
Adverse Effects
Warnings
Pregnancy
Pharmacology
Administration
Images
Patient Handout
Formulary

ergotamine/caffeine (Rx)

Dosing & Uses

Dosage Forms & Strengths

oral tablet (Cafergot)

rectal suppository (Migergot)

Vascular Headache

Oral

Rectal

Short-term prevention

Dosage Modifications

Renal or hepatic impairment

Dosing Considerations

Interactions

Interaction Checker

Contraindicated

Serious - Use Alternative

Significant - Monitor Closely

Minor

Contraindicated (33)

Serious - Use Alternative (122)

Monitor Closely (254)

Minor (46)

Adverse Effects

Frequency Not Defined

Cardiovascular

Warnings

Black Box Warnings

Contraindications

Cautions

Ergotism

Fibrotic complications

Drug interaction overview

CYP3A inhibitors

Pregnancy & Lactation

Pregnancy

Labor and delivery

Animal studies

Lactation

Pregnancy Categories

Pharmacology

Mechanism of Action

Absorption

Distribution

Metabolism

Elimination

Administration

Oral Administration

Rectal Administration

Storage

Tablets

Suppositories

Images

Patient Handout

Formulary

Plans

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