ergotamine/caffeine (Rx)

Brand and Other Names:Cafergot, Migergot

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

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Interactions

Interaction Checker

and ergotamine/caffeine

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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 (121)

            • amobarbital

              amobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • 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.

            • 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 (265)

            • 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.

            • elranatamab

              elranatamab will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

            • 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.

            • epcoritamab

              epcoritamab, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

            • 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.

            • glofitamab

              glofitamab, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

            • 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. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

            • 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.

            • lonapegsomatropin

              lonapegsomatropin decreases effects of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

            • 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.

            • pirtobrutinib

              pirtobrutinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pirtobrutinib (a CYP3A4 inhibitor) may increase plasma concentrations of sensitive CYP3A4 substrate which may increase the risk of adverse reactions related to these substrates.

            • 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).

            • ritlecitinib

              ritlecitinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP3A4 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP3A substrates.

            • 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.

            • solriamfetol

              caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • somapacitan

              somapacitan decreases effects of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

            • somatrogon

              somatrogon decreases effects of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

            • somatropin

              somatropin decreases effects of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates.

            • St John's Wort

              ergotamine and St John's Wort both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • talquetamab

              talquetamab will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

            • 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.

            • vonoprazan

              vonoprazan will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Vonoprazan is weak CYP3A inhibitor. Caution with sensitive CYP3A substrates.

            • 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 (40)

            • 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.

            • 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.

            • 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.

            • 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.

            Previous
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            Adverse Effects

            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
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            Warnings

            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
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            Pregnancy & Lactation

            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.

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            Pharmacology

            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)

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            Administration

            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
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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            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.
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            Code Definition
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            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.