ergotamine/caffeine (Rx)

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

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.

• 5-HTP

  Monitor Closely (1)5-HTP and ergotamine both increase serotonin levels. Use Caution/Monitor.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• adenosine

  Minor (1)caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• albuterol

  Monitor Closely (1)albuterol and caffeine both decrease sedation. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• almotriptan

  Contraindicated (1)ergotamine, almotriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)almotriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• alprazolam

  Monitor Closely (1)alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• amantadine

  Minor (1)amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  Minor (1)American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amitriptyline

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

• amobarbital

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

• amoxapine

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

• amyl nitrite

  Serious - Use Alternative (1)amyl nitrite increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  Serious - Use Alternative (1)aprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• arformoterol

  Monitor Closely (1)arformoterol and caffeine both decrease sedation. Use Caution/Monitor.

• aripiprazole

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

• armodafinil

  Monitor Closely (1)armodafinil and caffeine both decrease sedation. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)armodafinil will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)artemether/lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• asenapine

  Monitor Closely (1)ergotamine, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• atazanavir

  Serious - Use Alternative (2)atazanavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  atazanavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

• atogepant

  Monitor Closely (1)ergotamine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avapritinib

  Monitor Closely (1)ergotamine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axitinib

  Monitor Closely (1)ergotamine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  Monitor Closely (1)azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• azithromycin

  Minor (1)azithromycin increases levels of ergotamine by unknown mechanism. Minor/Significance Unknown.

• belladonna and opium

  Monitor Closely (1)belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benperidol

  Monitor Closely (1)benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benzphetamine

  Monitor Closely (1)caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, benzphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• berotralstat

  Monitor Closely (1)berotralstat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor or titrate substrate dose when berotralstat is coadministered with narrow therapeutic index drugs that are CYP3A substrates.

• bosentan

  Serious - Use Alternative (1)bosentan will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of ergotamine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brigatinib

  Serious - Use Alternative (1)brigatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• bromocriptine

  Serious - Use Alternative (1)ergotamine, bromocriptine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. The concomitant use of bromocriptine with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided.

• brompheniramine

  Monitor Closely (1)brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• budesonide

  Serious - Use Alternative (1)budesonide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• buprenorphine buccal

  Monitor Closely (1)buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bupropion

  Serious - Use Alternative (1)caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

• buspirone

  Monitor Closely (1)buspirone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• butabarbital

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

• butalbital

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

• butorphanol

  Monitor Closely (1)butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium acetate

  Minor (1)caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  Minor (1)caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

• calcium chloride

  Minor (1)caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  Minor (1)caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  Minor (1)caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• carbamazepine

  Minor (1)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)carbamazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• carbinoxamine

  Monitor Closely (1)carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)ergotamine, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• cenobamate

  Monitor Closely (1)cenobamate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Serious - Use Alternative (1)ceritinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose reduction.

• chloral hydrate

  Monitor Closely (1)chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (1)chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cigarette smoking

  Minor (1)cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cimetidine

  Minor (1)cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)cimetidine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cinnarizine

  Monitor Closely (1)cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ciprofloxacin

  Monitor Closely (1)ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

• citalopram

  Monitor Closely (1)citalopram and ergotamine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

• clarithromycin

  Contraindicated (1)clarithromycin increases toxicity of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration may result in vasospasm and ischemia of the extremities and other tissues including the CNS.Serious - Use Alternative (1)clarithromycin increases levels of ergotamine by decreasing metabolism. Contraindicated.

• clemastine

  Monitor Closely (1)clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clomipramine

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

• clonazepam

  Monitor Closely (1)clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clorazepate

  Monitor Closely (1)clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clotrimazole

  Minor (1)clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• clozapine

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

• cobicistat

  Contraindicated (1)cobicistat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)

• cocaine topical

  Monitor Closely (1)cocaine topical and ergotamine both increase serotonin levels. Use Caution/Monitor.

• codeine

  Monitor Closely (1)codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• conivaptan

  Serious - Use Alternative (1)conivaptan will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cortisone

  Serious - Use Alternative (1)cortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  Monitor Closely (1)cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Serious - Use Alternative (1)cyclosporine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cyproheptadine

  Monitor Closely (1)cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• darifenacin

  Serious - Use Alternative (1)darifenacin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darunavir

  Serious - Use Alternative (1)darunavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. "Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. "

• dasatinib

  Serious - Use Alternative (1)dasatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• deferasirox

  Monitor Closely (2)deferasirox will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use ergot alkaloids with caution with less potent CYP3A4 inhibitors.
  
  deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• desipramine

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

• desvenlafaxine

  Serious - Use Alternative (1)ergotamine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• dexamethasone

  Serious - Use Alternative (1)dexamethasone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.
  
  dexfenfluramine and ergotamine both increase serotonin levels. Use Caution/Monitor.Serious - Use Alternative (2)dexfenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.
  
  ergotamine, dexfenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dexmethylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dextroamphetamine

  Monitor Closely (2)dextroamphetamine and ergotamine both increase serotonin levels. Use Caution/Monitor.
  
  caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dextroamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dextromethorphan

  Monitor Closely (1)dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dextromoramide

  Monitor Closely (1)dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• DHEA, herbal

  Serious - Use Alternative (1)DHEA, herbal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diamorphine

  Monitor Closely (1)diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (1)caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, diethylpropion. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)dihydroergotamine and ergotamine both increase serotonin levels. Use Caution/Monitor.

• dihydroergotamine intranasal

  Monitor Closely (1)dihydroergotamine intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (1)diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipyridamole

  Serious - Use Alternative (1)caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.

• dobutamine

  Monitor Closely (1)dobutamine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dobutamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dopamine

  Monitor Closely (1)caffeine and dopamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, dopamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dopexamine

  Monitor Closely (1)dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

• doxepin

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

• dronedarone

  Serious - Use Alternative (1)dronedarone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• droperidol

  Monitor Closely (1)droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• droxidopa

  Monitor Closely (1)caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  Monitor Closely (1)duloxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• efavirenz

  Serious - Use Alternative (2)efavirenz will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  efavirenz increases levels of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Competitive inhibition of CYP3A4 might lead to vasospasm and ischemia.

• elagolix

  Monitor Closely (1)elagolix will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered.

• eletriptan

  Contraindicated (1)ergotamine, eletriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)eletriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• elranatamab

  Monitor Closely (1)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

  Monitor Closely (1)eluxadoline increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Contraindicated (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enzalutamide

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• epcoritamab

  Monitor Closely (1)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

  Monitor Closely (1)ephedrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, ephedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• epinephrine

  Monitor Closely (1)epinephrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, epinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• epinephrine inhaled

  Monitor Closely (1)caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (1)epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (1)erythromycin base will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

• eslicarbazepine acetate

  Serious - Use Alternative (1)eslicarbazepine acetate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• estazolam

  Monitor Closely (1)estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• etravirine

  Serious - Use Alternative (1)etravirine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• eucalyptus

  Minor (1)eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fenfluramine

  Monitor Closely (3)ergotamine and fenfluramine both increase serotonin levels. Use Caution/Monitor.
  
  caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.
  
  ergotamine decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.Serious - Use Alternative (2)fenfluramine, ergotamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of serotonin syndrome.
  
  ergotamine, fenfluramine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ferric maltol

  Monitor Closely (1)ferric maltol, ergotamine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fexinidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fezolinetant

  Contraindicated (1)caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• finerenone

  Monitor Closely (1)ergotamine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  Monitor Closely (1)ergotamine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• fluconazole

  Minor (1)fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)fluconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fludrocortisone

  Serious - Use Alternative (1)fludrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fluoxetine

  Monitor Closely (1)fluoxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• fluphenazine

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

• flurazepam

  Monitor Closely (1)flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (2)fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  fluvoxamine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• formoterol

  Monitor Closely (1)formoterol and caffeine both decrease sedation. Use Caution/Monitor.

• fosamprenavir

  Serious - Use Alternative (2)fosamprenavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  fosamprenavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

• fosaprepitant

  Serious - Use Alternative (1)fosaprepitant will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fosphenytoin

  Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• frovatriptan

  Contraindicated (1)ergotamine, frovatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)frovatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

• glofitamab

  Monitor Closely (1)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

  Monitor Closely (1)glycerol phenylbutyrate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.

• glyceryl trinitrate pr

  Contraindicated (1)ergotamine decreases effects of glyceryl trinitrate pr by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)glyceryl trinitrate pr increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• grapefruit

  Minor (1)grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)grapefruit will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• green tea

  Monitor Closely (1)green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.Minor (1)green tea increases levels of ergotamine by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Due to caffeine content.

• griseofulvin

  Serious - Use Alternative (1)griseofulvin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• guarana

  Minor (1)guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• guselkumab

  Monitor Closely (1)guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

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

• hydrocortisone

  Serious - Use Alternative (1)hydrocortisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• hydromorphone

  Monitor Closely (1)hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (1)hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iloperidone

  Monitor Closely (3)iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  ergotamine, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  iloperidone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imipramine

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

• indinavir

  Serious - Use Alternative (2)indinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
  
  indinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• iobenguane I 131

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

• isavuconazonium sulfate

  Monitor Closely (2)ergotamine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isavuconazonium sulfate will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Contraindicated (1)isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)isocarboxazid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.

• isoniazid

  Monitor Closely (1)ergotamine and isoniazid both increase serotonin levels. Use Caution/Monitor.Serious - Use Alternative (1)isoniazid will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isoproterenol

  Monitor Closely (1)isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, isoproterenol. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• isosorbide dinitrate

  Serious - Use Alternative (1)isosorbide dinitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• isosorbide mononitrate

  Serious - Use Alternative (1)isosorbide mononitrate increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Contraindicated (1)itraconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increased risk of ergotism leading to cerebral ischemia and/or ischemia of the extremitiesMinor (1)itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ketoconazole

  Contraindicated (1)ketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ketotifen, ophthalmic

  Monitor Closely (1)ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• L-tryptophan

  Monitor Closely (1)ergotamine and L-tryptophan both increase serotonin levels. Use Caution/Monitor.

• lapatinib

  Serious - Use Alternative (1)lapatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• larotrectinib

  Monitor Closely (1)larotrectinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lemborexant

  Monitor Closely (1)ergotamine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

• lenacapavir

  Serious - Use Alternative (2)lenacapavir will increase the level or effect of ergotamine by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Coadministration of lenacapavir with dihydroergotamine, ergotamine or methylergonovine is not recommended.
  
  lenacapavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• letermovir

  Contraindicated (1)letermovir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of letermovir and ergot alkaloids is contraindicated due to risk of ergotism.Monitor Closely (1)letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (1)levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• levoketoconazole

  Contraindicated (1)levoketoconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• levomilnacipran

  Monitor Closely (1)levomilnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• levorphanol

  Monitor Closely (1)levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. 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.

• linezolid

  Contraindicated (1)linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)linezolid and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

• lisdexamfetamine

  Monitor Closely (1)caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, lisdexamfetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• lithium

  Monitor Closely (1)ergotamine and lithium both increase serotonin levels. Use Caution/Monitor.

• lofepramine

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

• lofexidine

  Monitor Closely (1)lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lomitapide

  Monitor Closely (1)ergotamine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)ergotamine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• lonapegsomatropin

  Monitor Closely (1)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.

• lopinavir

  Serious - Use Alternative (1)lopinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• loprazolam

  Monitor Closely (1)loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lorazepam

  Monitor Closely (1)lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lorlatinib

  Serious - Use Alternative (1)lorlatinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.

• lormetazepam

  Monitor Closely (1)lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine

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

• loxapine inhaled

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

• lsd

  Monitor Closely (1)ergotamine and lsd both increase serotonin levels. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• lumefantrine

  Serious - Use Alternative (1)lumefantrine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lurasidone

  Monitor Closely (1)ergotamine, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• maprotiline

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

• marijuana

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

• melatonin

  Monitor Closely (1)melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meperidine

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

• meprobamate

  Monitor Closely (1)meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (1)metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (1)methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (1)caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, methamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• methotrexate

  Monitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.

• methylene blue

  Serious - Use Alternative (1)methylene blue and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

• methylenedioxymethamphetamine

  Monitor Closely (1)caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, methylenedioxymethamphetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• methylphenidate

  Monitor Closely (1)caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.Serious - Use Alternative (1)ergotamine, methylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• methylprednisolone

  Serious - Use Alternative (1)methylprednisolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• metronidazole

  Serious - Use Alternative (1)metronidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mexiletine

  Minor (1)mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)miconazole vaginal will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• midazolam

  Monitor Closely (1)midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)ergotamine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• midodrine

  Monitor Closely (1)caffeine and midodrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, midodrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• mifepristone

  Contraindicated (1)mifepristone increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with CYP3A substrates that have a narrow therapeutic index .

• milnacipran

  Monitor Closely (1)milnacipran and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• minocycline

  Monitor Closely (1)minocycline, ergotamine. Either increases toxicity of the other by Mechanism: unknown. Use Caution/Monitor. coadministration of ergot alkaloids and tetracyclines increases risk of ergotism.

• mirtazapine

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

• mitotane

  Monitor Closely (1)mitotane decreases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• modafinil

  Monitor Closely (1)caffeine and modafinil both decrease sedation. Use Caution/Monitor.

• molindone

  Monitor Closely (1)ergotamine, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• morphine

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

• motherwort

  Monitor Closely (1)motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxonidine

  Monitor Closely (1)moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• naratriptan

  Contraindicated (1)ergotamine, naratriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)naratriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• nefazodone

  Monitor Closely (1)nefazodone and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)nefazodone will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nelfinavir

  Serious - Use Alternative (2)nelfinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
  
  nelfinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nevirapine

  Serious - Use Alternative (1)nevirapine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nicorandil

  Serious - Use Alternative (1)nicorandil increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nifedipine

  Serious - Use Alternative (1)nifedipine will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nilotinib

  Serious - Use Alternative (1)nilotinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• nirmatrelvir

  Contraindicated (1)nirmatrelvir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• nirmatrelvir/ritonavir

  Contraindicated (1)nirmatrelvir/ritonavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions.

• nitroglycerin IV

  Contraindicated (1)ergotamine decreases effects of nitroglycerin IV by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin IV increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nitroglycerin PO

  Serious - Use Alternative (1)nitroglycerin PO increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nitroglycerin rectal

  Monitor Closely (1)nitroglycerin rectal will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and consequently increases its oral bioavailability. Ergotamine is known to precipitate angina pectoris. Therefore the possibility of ergotism in patients receiving nitroglycerin should be considered.

• nitroglycerin sublingual

  Contraindicated (1)ergotamine decreases effects of nitroglycerin sublingual by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin sublingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nitroglycerin topical

  Contraindicated (1)ergotamine decreases effects of nitroglycerin topical by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin topical increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nitroglycerin transdermal

  Contraindicated (1)ergotamine decreases effects of nitroglycerin transdermal by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin transdermal increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• nitroglycerin translingual

  Contraindicated (1)ergotamine decreases effects of nitroglycerin translingual by pharmacodynamic antagonism. Contraindicated.Serious - Use Alternative (1)nitroglycerin translingual increases effects of ergotamine by decreasing metabolism. Avoid or Use Alternate Drug. Risk of increased SBP, angina pectoris.

• norepinephrine

  Monitor Closely (1)norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, norepinephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• nortriptyline

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

• olanzapine

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

• olutasidenib

  Serious - Use Alternative (1)olutasidenib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• omaveloxolone

  Monitor Closely (1)omaveloxolone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Contraindicated (1)ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Acute ergot toxicity characterized by vasospasm and tissue ischemia has been associated with coadministration of ritonavir

• opium tincture

  Monitor Closely (1)opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxcarbazepine

  Serious - Use Alternative (1)oxcarbazepine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• oxycodone

  Monitor Closely (1)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (1)oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (1)ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• pacritinib

  Serious - Use Alternative (1)pacritinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• palbociclib

  Monitor Closely (1)palbociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib

• paliperidone

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

• papaveretum

  Monitor Closely (1)papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• paroxetine

  Monitor Closely (1)paroxetine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• pefloxacin

  Monitor Closely (1)pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• peginterferon alfa 2a

  Minor (1)peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pentazocine

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

• pentobarbital

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

• perphenazine

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

• pexidartinib

  Serious - Use Alternative (1)pexidartinib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 inducer) with sensitive CYP3A substrates may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.

• phendimetrazine

  Monitor Closely (1)caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phendimetrazine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• phenelzine

  Contraindicated (1)phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)phenelzine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.

• phenobarbital

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

• phentermine

  Monitor Closely (1)caffeine and phentermine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• phenylephrine

  Monitor Closely (1)caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• phenylephrine PO

  Monitor Closely (1)caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, phenylephrine PO. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• phenytoin

  Serious - Use Alternative (1)phenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• pholcodine

  Monitor Closely (1)pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimavanserin

  Monitor Closely (1)ergotamine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• pimozide

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

• pipemidic acid

  Minor (1)pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (1)pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

• pirtobrutinib

  Monitor Closely (1)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

  Monitor Closely (1)pitolisant will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

• posaconazole

  Minor (1)posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)posaconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• prednisone

  Serious - Use Alternative (1)prednisone will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• primidone

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

• procarbazine

  Contraindicated (1)procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.Serious - Use Alternative (1)procarbazine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.

• prochlorperazine

  Monitor Closely (1)prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (1)caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, propylhexedrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• protriptyline

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

• pseudoephedrine

  Contraindicated (1)ergotamine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Ergot derivatives may enhance the vasoconstricting effect of pseudoephedrine and eventually significantly increasing blood pressure.

• quazepam

  Monitor Closely (1)quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

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

• quinupristin/dalfopristin

  Serious - Use Alternative (1)quinupristin/dalfopristin will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rasagiline

  Monitor Closely (2)rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
  
  rasagiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• regadenoson

  Serious - Use Alternative (1)caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

• rifabutin

  Serious - Use Alternative (1)rifabutin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Minor (1)rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)rifampin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifapentine

  Serious - Use Alternative (1)rifapentine will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• risperidone

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

• ritlecitinib

  Monitor Closely (1)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.

• ritonavir

  Serious - Use Alternative (2)ritonavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  ritonavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

• rizatriptan

  Contraindicated (1)ergotamine, rizatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)rizatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• ropeginterferon alfa 2b

  Monitor Closely (1)ropeginterferon alfa 2b will increase the level or effect of ergotamine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rucaparib

  Monitor Closely (2)rucaparib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
  
  rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

• rufinamide

  Serious - Use Alternative (1)rufinamide will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ruxolitinib

  Minor (1)ergotamine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)ergotamine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

  Minor (1)sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

• SAMe

  Monitor Closely (1)ergotamine and SAMe both increase serotonin levels. Use Caution/Monitor.

• saquinavir

  Serious - Use Alternative (2)saquinavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
  
  saquinavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• schisandra

  Monitor Closely (1)schisandra will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• scullcap

  Monitor Closely (1)scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• secobarbital

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

• selegiline

  Monitor Closely (2)selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
  
  selegiline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Monitor Closely (1)selegiline transdermal and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• serdexmethylphenidate/dexmethylphenidate

  Serious - Use Alternative (1)ergotamine, serdexmethylphenidate/dexmethylphenidate. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• sertraline

  Monitor Closely (1)sertraline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• shepherd's purse

  Monitor Closely (1)shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• smoking

  Minor (1)smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• sofosbuvir/velpatasvir

  Monitor Closely (1)sofosbuvir/velpatasvir increases levels of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

• solriamfetol

  Monitor Closely (1)caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• somapacitan

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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.

• sotorasib

  Serious - Use Alternative (1)sotorasib will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

• St John's Wort

  Monitor Closely (1)ergotamine and St John's Wort both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (2)stiripentol, ergotamine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

• sufentanil

  Monitor Closely (1)sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sumatriptan

  Contraindicated (1)ergotamine, sumatriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)sumatriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.

• sumatriptan intranasal

  Contraindicated (1)ergotamine, sumatriptan intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)sumatriptan intranasal and ergotamine both increase serotonin levels. Use Caution/Monitor.

• talquetamab

  Monitor Closely (1)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

  Monitor Closely (1)tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tazemetostat

  Monitor Closely (2)tazemetostat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ergotamine will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teclistamab

  Monitor Closely (1)teclistamab will increase the level or effect of ergotamine by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• telotristat ethyl

  Monitor Closely (1)telotristat ethyl will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

• temazepam

  Monitor Closely (1)temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• terbutaline

  Monitor Closely (1)terbutaline and caffeine both decrease sedation. Use Caution/Monitor.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• thiamine

  Minor (1)caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  Monitor Closely (1)thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thiothixene

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

• tinidazole

  Monitor Closely (1)ergotamine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Serious - Use Alternative (2)tipranavir increases levels of ergotamine by decreasing metabolism. Contraindicated.
  
  tipranavir will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• tobacco use

  Minor (1)tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• topiramate

  Monitor Closely (1)topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)topiramate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tramadol

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

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)tranylcypromine and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug.

• trazodone

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

• triamcinolone acetonide injectable suspension

  Serious - Use Alternative (1)triamcinolone acetonide injectable suspension will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• triazolam

  Monitor Closely (1)triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

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

• trimipramine

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

• triprolidine

  Monitor Closely (1)triprolidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trofinetide

  Monitor Closely (1)trofinetide will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• turmeric

  Monitor Closely (1)turmeric will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ustekinumab

  Monitor Closely (1)ustekinumab, ergotamine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• venlafaxine

  Monitor Closely (1)venlafaxine and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• verapamil

  Minor (1)verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)verapamil will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• vonoprazan

  Monitor Closely (1)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.

• voriconazole

  Contraindicated (1)voriconazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Minor (1)voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• xylometazoline

  Monitor Closely (1)caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, xylometazoline. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• yerba mate

  Minor (1)yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• yohimbine

  Monitor Closely (1)caffeine and yohimbine both decrease sedation. Use Caution/Monitor.Serious - Use Alternative (1)ergotamine, yohimbine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• zafirlukast

  Serious - Use Alternative (1)zafirlukast will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ziconotide

  Monitor Closely (1)ziconotide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zileuton

  Minor (1)zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ziprasidone

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

• zolmitriptan

  Contraindicated (1)ergotamine, zolmitriptan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Additive vasospasm. Sep. by 24h.Monitor Closely (1)zolmitriptan and ergotamine both increase serotonin levels. Use Caution/Monitor.