DHE 45

Ergot Alkaloids

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 2
Approved by FDA after NIOSH 2016 list published.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Administer IV hydration and premedication with an antiemetic prior to administration.
Administer via slow IV push; in pediatric patients, give dose over 3 minutes.

Nasal spray assembly
Each vial contains 1 complete dose.
Assemble the nasal spray applicator immediately prior to use.
Storage: Use within 8 hours after the vial is opened or the product has been assembled.
 
Nasal spray administration (Migranal and generic equivalents)
Prime the nasal spray device before administration by releasing 4 sprays. Use the spray immediately after priming.
Do not have patient tilt head back or sniff while spraying or immediately after.
Spray once in each nostril. Wait 15 minutes, spray once again in each nostril.
Storage: Discard the nasal spray pump with the vial after use.
 
Nasal spray administration (Trudhesa)
Prime the nasal spray device before administration by releasing 4 sprays. Use the spray immediately after priming.
Make sure the patient's head is straight and the nasal spray device is upright. Sniffing while or after dosing is not necessary; however, it will not cause harm or make the medicine less effective.
Spray once in each nostril.
Prepare a new nasal spray device for a second dose, if needed.
Storage: Discard the assembled nasal spray device immediately after use.

cardiac valvulopathy / Delayed / 0-1.0
visual impairment / Early / 0.1-1.0
bronchospasm / Rapid / 0-0.1
ventricular fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
cyanosis / Early / Incidence not known
bowel ischemia / Delayed / Incidence not known
coronary vasospasm / Early / Incidence not known
acute myocardial ischemia / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
retroperitoneal fibrosis / Delayed / Incidence not known

sinus tachycardia / Rapid / 0.1-1.0
palpitations / Early / 0.1-1.0
edema / Delayed / 0.1-1.0
confusion / Early / 0.1-1.0
euphoria / Early / 0.1-1.0
dyspnea / Early / 0.1-1.0
dysphagia / Delayed / 0.1-1.0
dystonic reaction / Delayed / 0.1-1.0
hot flashes / Early / 1.0-1.0
conjunctivitis / Delayed / 0.1-1.0
photophobia / Early / 0.1-1.0
cystitis / Delayed / 0.1-1.0
peripheral vasoconstriction / Rapid / 0-0.1
angina / Early / 0-0.1
hypotension / Rapid / 0-0.1
migraine / Early / 0-0.1
depression / Delayed / 0-0.1
vaginitis / Delayed / 0-0.1
hypertension / Early / Incidence not known
withdrawal / Early / Incidence not known
medication overuse headache / Delayed / Incidence not known

rhinitis / Early / 19.0-26.0
pharyngitis / Delayed / 3.0-21.0
nausea / Early / 10.0-10.0
dysgeusia / Early / 6.0-8.0
sinusitis / Delayed / 1.0-5.0
dizziness / Early / 4.0-4.0
vomiting / Early / 4.0-4.0
drowsiness / Early / 3.0-3.0
epistaxis / Delayed / 0-3.0
paresthesias / Delayed / 2.0-2.0
diarrhea / Early / 2.0-2.0
hypoesthesia / Delayed / 0.1-1.0
tremor / Early / 0.1-1.0
vertigo / Early / 0.1-1.0
insomnia / Early / 0.1-1.0
infection / Delayed / 0.1-1.0
rhinorrhea / Early / 1.0-1.0
hiccups / Early / 0.1-1.0
xerostomia / Early / 1.0-1.0
dyspepsia / Early / 0.1-1.0
abdominal pain / Early / 0.1-1.0
myalgia / Early / 0.1-1.0
muscle cramps / Delayed / 0.1-1.0
weakness / Early / 0.1-1.0
petechiae / Delayed / 0.1-1.0
pruritus / Rapid / 0.1-1.0
rash / Early / 0.1-1.0
malaise / Early / 0.1-1.0
chills / Rapid / 0.1-1.0
fever / Early / 0.1-1.0
asthenia / Delayed / 1.0-1.0
fatigue / Early / 1.0-1.0
tinnitus / Delayed / 0.1-1.0
lacrimation / Early / 0.1-1.0
dysosmia / Delayed / 0.1-1.0
otalgia / Early / 0.1-1.0
increased urinary frequency / Early / 0.1-1.0
gait disturbance / Delayed / 0-0.1
hyperkinesis / Delayed / 0-0.1
anxiety / Delayed / 0-0.1
anorexia / Delayed / 0-0.1
hypersalivation / Early / 0-0.1
arthralgia / Delayed / 0-0.1
urticaria / Rapid / 0-0.1
maculopapular rash / Early / 0-0.1
yawning / Early / 0-0.1
ocular pain / Early / 0-0.1
pallor / Early / Incidence not known
flushing / Rapid / Incidence not known
headache / Early / Incidence not known
throat irritation / Early / Incidence not known
nasal irritation / Early / Incidence not known
nasal congestion / Early / Incidence not known
nasal dryness / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known

DHE 45, Migranal, TRUDHESA

Rx

Parenteral and nasally administered ergotamine derivative
Used for the treatment of acute migraine with or without aura and cluster headache
Associated with serious adverse cardiac and cerebrovascular events; cardiovascular evaluation recommended prior to starting therapy

1 mg IV as a single dose. May repeat dose every 1 hour as needed. Max: 2 mg/day and 6 mg/week. Guidelines classify parenteral dihydroergotamine as having probable efficacy for the treatment of acute migraine.

Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 1 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.2 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.

Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 1 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.15 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.

Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 0.5 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.15 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.

Select low or high dose protocol based on patient tolerability. If no improvement seen after 5 doses, discontinue therapy. If improvement is seen, continue until headache ceases and give 1 additional dose, up to the maximum number of doses. HIGH DOSE: 0.5 mg IV every 8 hours. Max: 20 doses. Some experts recommend an initial test dose (one-half of the appropriate dose); if tolerated give the remainder of the dose 30 minutes later. LOW DOSE: 0.1 mg IV every 6 hours. May increase by 0.05 mg/dose until the patient has mild abdominal discomfort. Max: 8 to 16 doses.

1 mg IM or subcutaneously as a single dose. May repeat dose every 1 hour as needed. Max: 3 mg/day and 6 mg/week. Guidelines classify parenteral dihydroergotamine as having probable efficacy for the treatment of acute migraine.

0.5 mg in each nostril, followed by 0.5 mg in each nostril 15 minutes later for a total dose of 2 mg. Studies have shown no additional benefit from acute doses more than 2 mg for a single migraine episode. The safety of doses more than 3 mg/day and 4 mg/week have not been established. Guidelines classify intranasal dihydroergotamine as having established efficacy for the treatment of acute migraine.

0.725 mg in each nostril as a single dose. May repeat dose after at least 1 hour after the first dose if needed. Max: 2.9 mg/day and 4.35 mg/week. Guidelines classify intranasal dihydroergotamine as having established efficacy for the treatment of acute migraine.

1 mg IV once. May repeat dose every 1 hour as needed. Max: 2 mg/day and 6 mg/week.

1 mg IM or subcutaneously once. May repeat dose every 1 hour as needed. Max: 3 mg/day and 6 mg/week.

Use is contraindicated in patients with severe hepatic impairment.

Use is contraindicated in patients with severe renal impairment.

Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acrivastine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Adagrasib: (Contraindicated) Coadministration of ergot alkaloids and adagrasib is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and adagrasib is a strong CYP3A inhibitor.
Almotriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Amiodarone: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of amiodarone is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and amiodarone is a moderate CYP3A inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Amphetamine; Dextroamphetamine Salts: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Aprepitant, Fosaprepitant: (Major) Use caution if ergot alkaloids and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ergot alkaloid-related adverse effects (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects) for several days after administration of a multi-day aprepitant regimen. Ergot alkaloids are CYP3A4 substrates. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ergot alkaloids. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Benzphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Berotralstat: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and berotralstat. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Bromocriptine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Brompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Ceritinib: (Contraindicated) Concomitant use of ergotamine with ceritinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Cetirizine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Ciprofloxacin: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of ciprofloxacin is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and ciprofloxacin is a moderate CYP3A inhibitor.
Citalopram: (Moderate) Use citalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Cobicistat: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Cocaine: (Contraindicated) Concomitant use of ergotamine with cocaine is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Conivaptan: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of conivaptan is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and crizotinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Danazol: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Delavirdine: (Contraindicated) The concurrent use of delavirdine is contraindicated with ergot alkaloids. This is because delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as ergot alkaloids, should be expected with concurrent use of delavirdine. This could cause ergot toxicity.
Desloratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Desvenlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Dexbrompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Diltiazem: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of diltiazem is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and diltiazem is a moderate CYP3A inhibitor.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension.
Dronedarone: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and dronedarone. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
Duloxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Eletriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of ergotamine with cobicistat is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Erythromycin: (Contraindicated) Coadministration of ergot alkaloids and erythromycin is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and erythromycin is a CYP3A inhibitor.
Escitalopram: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Fedratinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and fedratinib. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Fexofenadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Fluconazole: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of fluconazole is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and fluconazole is a moderate CYP3A inhibitor.
Fluoxetine: (Moderate) Use fluoxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Fluvoxamine: (Moderate) Use fluvoxamine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Frovatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Grapefruit juice: (Major) The risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects) is potentially increased by the use of CYP3A4 inhibitors. Grapefruit juice may decrease dihydroergotamine metabolism via CYP3A4. Patients should probably use caution with grapefruit juice by not modifying their usual grapefruit juice intake while taking dihydroergotamine. Elderly patients have the greatest possibility of ingesting grapefruit and interacting medications and are the most vulnerable to the adverse clinical consequences. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level.
Green Tea: (Minor) Advise patients to consider avoiding excess caffeine intake via dietary supplements while taking ergotamine. The net effect of excess caffeine intake on ergotamine efficacy and adverse effects is unclear and likely to vary based on the amount of caffeine ingested and timing of consumption. Oral caffeine has been observed to increase the rate and extent of absorption of oral ergotamine which may increase overall ergotamine exposure. Additionally, caffeine is a cranial vasoconstrictor. Concomitant use may improve ergotamine efficacy or cause a synergistic increase in blood pressure and increase the risk for vasospastic adverse effects including cerebral or peripheral ischemia.
Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Hydrocodone; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Idelalisib: (Contraindicated) Concomitant use of ergotamine with idelalisib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Imatinib: (Contraindicated) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 3A4 and may increase concentrations of other drugs metabolized by this enzyme Coadministration of ergotamine with potent inhibitors of CYP3A4 is considered contraindicated due to the risk of acute ergot toxicity.
Isavuconazonium: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and isavuconazonium. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and isavuconazole, the active moiety of isavuconazonium, is a moderate CYP3A inhibitor.
Isoproterenol: (Contraindicated) Concomitant use of ergotamine with isoproterenol is contraindicated as due to the risk for a synergistic increase in blood pressure. Coadministration may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Itraconazole: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as itraconazole, or administration for 2 weeks after discontinuation of itraconazole treatment is contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Ketoconazole: (Contraindicated) Coadministration of ergot alkaloids and ketoconazole is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and ketoconazole is a strong CYP3A inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Lefamulin: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and lefamulin. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and lefamulin is a moderate CYP3A inhibitor.
Lenacapavir: (Major) Avoid concomitant use of ergot alkaloids and lenacapavir and consider alternative therapy. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities.
Letermovir: (Contraindicated) Concurrent administration of ergot alkaloids and letermovir is contraindicated due to the risk of ergotism. Taking these drugs together may result in increased concentrations of ergot alkaloids due to inhibition of CYP3A4 by letermovir.
Levoketoconazole: (Contraindicated) Coadministration of ergot alkaloids and ketoconazole is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and ketoconazole is a strong CYP3A inhibitor.
Levomilnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Linezolid: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
Lisdexamfetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Lonafarnib: (Contraindicated) Concomitant use of ergotamine with lonafarnib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor.
Loratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Mepivacaine: (Major) If epinephrine is added to mepivacaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
Methamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Methylene Blue: (Moderate) Theoretically, concurrent use of methylene blue and ergot alkaloids may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and ergot alkaloids increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
Mifepristone: (Contraindicated) Coadministration of ergot alkaloids and mifepristone is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and mifepristone is a strong CYP3A inhibitor.
Milnacipran: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Mirtazapine: (Moderate) The use of ergot alkaloids with mirtazapine might increase the risk for serotonin syndrome. Patients receiving ergot alkaloids with mirtazapine should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, discontinue serotonergic agents and institute appropriate medical treatment.
Naproxen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Naratriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Nefazodone: (Contraindicated) Concomitant use of ergotamine with nefazodone is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nicotine: (Major) Advise patients to avoid nicotine while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction.
Nilotinib: (Moderate) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and ergot alkaloids (e.g., ergotamine, dihydroergotamine), CYP3A4 substrates with a narrow therapeutic range, may result in increased ergot alkaloid levels. Avoid co-use when possible; consider alternative therapy to the ergot medication. Be alert for symptoms of ergot toxicity if these drugs together is medically necessary. An ergot alkaloid dose reduction may be necessary if these drugs are used together.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and ergot alkaloids is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase ergot alkaloids' exposure resulting in increased toxicity. Ergot alkaloids are CYP3A substrates and nirmatrelvir is a CYP3A inhibitor.
Nitrates: (Major) Avoid concomitant use of oral nitrates and ergot alkaloids. If concomitant use is unavoidable, monitor for ergot toxicity. Oral administration of nitrates markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is also known to precipitate angina pectoris and may cause vasoconstriction that reduces the efficacy of nitrates.
Olanzapine; Fluoxetine: (Moderate) Use fluoxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Paroxetine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Phentermine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable.
Phentermine; Topiramate: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable.
Posaconazole: (Contraindicated) Coadministration of ergot alkaloids with inhibitors of CYP3A4, such as posaconazole, is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Cabergoline may be minimally eliminated by the CYP isoenzyme system; therefore, interactions may be less than that of other ergot alkaloids.
Propranolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and propranolol. Propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating properties of epinephrine.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions including cerebral and peripheral ischemia during concomitant use of ergotamine and propranolol. Propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating properties of epinephrine.
Protease inhibitors: (Contraindicated) Coadministration of ergot alkaloids with potent inhibitors of CYP3A4, like anti-retroviral protease inhibitors is considered contraindicated due to the risk of acute ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Several case reports have established the clinical significance of this interaction in the medical literature. In some cases, fatal interactions have occurred.
Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Pseudoephedrine; Triprolidine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Ranolazine: (Major) In vitro studies indicate that ranolazine and its metabolite are inhibitors of CYP3A isoenzymes. The impact of coadministering ranolazine with other CYP3A4 substrates has not been studied. Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates, such as ergot alkaloids, potentially leading to adverse reactions.
Ribociclib: (Contraindicated) Concomitant use of ergotamine with ribociclib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Contraindicated) Concomitant use of ergotamine with ribociclib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ritlecitinib: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of ritlecitinib is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and ritlecitinib is a moderate CYP3A inhibitor.
Rizatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Serotonin-Receptor Agonists: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sertraline: (Moderate) Use sertraline and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Sumatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sumatriptan; Naproxen: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction. Nicotine acts indirectly as a sympathomimetic agent by releasing catecholamines, potentially resulting in effects such as hypertension, coronary spasm, coronary ischemia, or cardiac arrhythmias, which may be additive with ergot alkaloids.
Trandolapril; Verapamil: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of verapamil is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and verapamil is a moderate CYP3A inhibitor.
Tucatinib: (Contraindicated) Concomitant use of ergotamine with tucatinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor.
Vasopressors: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
Venlafaxine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering serotonin norepinephrine reuptake inhibitors (SNRIs) with other drugs that have serotonergic properties, such as the ergot alkaloids. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with serotonin reuptake inhibitors, which may be indicative of serotonin excess. Inform patients of the potential risk and monitor for serotonin syndrome. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Verapamil: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of verapamil is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and verapamil is a moderate CYP3A inhibitor.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vilazodone with other drugs that have serotonergic properties such as ergot alkaloids (e.g., ergotamine or dihydroergotamine). Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and an ergot alkaloid should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and the ergot alkaloid should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of ergotamine with clarithromycin is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Voriconazole: (Contraindicated) Concurrent administration of voriconazole with ergot alkaloids is contraindicated. Voriconazole may reduce the metabolism of the ergot alkaloids via inhibition of the hepatic CYP3A4 isoenzyme, potentially increasing the risk of ergotism (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia, or other serious effects).
Vortioxetine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering vortioxetine with other drugs that have serotonergic properties such as ergot alkaloids (e.g., ergotamine or dihydroergotamine). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.
Voxelotor: (Moderate) Monitor for an increase in ergotamine-related adverse effects and adjust the ergot alkaloid dosage as necessary if concomitant use of voxelotor is required. Concomitant use may increase the systemic exposure of ergot alkaloids and increase the risk for adverse reactions such as vasospasm which may lead to cerebral ischemia and ischemia of the extremities. Ergot alkaloids are CYP3A substrates and voxelotor is a moderate CYP3A inhibitor.
Zolmitriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.

DHE 45/Dihydroergotamine/Dihydroergotamine Mesylate Intramuscular Inj Sol: 1mg, 1mL
DHE 45/Dihydroergotamine/Dihydroergotamine Mesylate Intravenous Inj Sol: 1mg, 1mL
DHE 45/Dihydroergotamine/Dihydroergotamine Mesylate Subcutaneous Inj Sol: 1mg, 1mL
Dihydroergotamine/Dihydroergotamine Mesylate/Migranal/TRUDHESA Nasal Spray Met: 1mL, 4mg

3 mg/day IM or subcutaneous or 2 mg/day IV and 6 mg/week IV/IM/subcutaneous; 3 mg/day and 4 mg/week intranasal (Migranal and generic equivalents) or 2.9 mg/day and 4.35 mg/week intranasal (Trudhesa).

3 mg/day IM or subcutaneous or 2 mg/day IV and 6 mg/week IV/IM/subcutaneous; 3 mg/day and 4 mg/week intranasal (Migranal and generic equivalents) or 2.9 mg/day and 4.35 mg/week intranasal (Trudhesa).

Safety and efficacy have not been established; however, doses up to 1 mg/dose IV or 3 mg/day IV have been used off-label.

10 to 12 years weighing 25 kg or more: Safety and efficacy have not been established; however, doses up to 1 mg/dose IV or 3 mg/day IV have been used off-label.
10 to 12 years weighing less than 25 kg: Safety and efficacy have not been established; however, doses up to 0.5 mg/dose IV or 1.5 mg/day IV have been used off-label.
6 to 9 years: Safety and efficacy have not been established; however, doses up to 0.5 mg/dose IV or 1.5 mg/day IV have been used off-label.
1 to 5 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Dihydroergotamine binds with high affinity to 5-HT1D receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, alpha1 and alpha2-adrenergic receptors, and dopamine D2L and D3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5HT1D receptors. It is hypothesized that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. An alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

Dihydroergotamine is administered parenterally or intranasally. Dihydroergotamine is 93% bound to plasma protein, and the apparent steady-state Vd is approximately 800 L. The major metabolite, 8'-beta-hydroxy dihydroergotamine, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance. After intranasal administration, total metabolites represent only 20% to 30% of plasma AUC. The major excretory route of dihydroergotamine is via the bile in the feces. The total body clearance is 1.5 L/minute, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged dihydroergotamine is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/minute) is unaffected by the route of dihydroergotamine administration. The decline of plasma dihydroergotamine after intramuscular or intravenous administration is multi-exponential with a terminal half-life of about 9 hours. The decline of plasma dihydroergotamine after nasal administration is biphasic with a half-life of about 10 to 12 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Dihydroergotamine is a substrate for CYP3A4.

After administration of dihydroergotamine 1 mg IV in healthy adults, Tmax was approximately 1 to 2 minutes and Cmax was less than 10 ng/mL.

No difference was observed in dihydroergotamine bioavailability from intramuscular and subcutaneous doses. Bioavailability after intramuscular administration is 100%. After administration of dihydroergotamine 1 mg IM in healthy adults, Tmax was 24 minutes and Cmax was 2.9 ng/mL.

Absolute bioavailability for subcutaneous administration have not been determined. However, no difference was observed in dihydroergotamine bioavailability from intramuscular and subcutaneous doses.

Intranasal Route
Absorption of dihydroergotamine is variable after intranasal administration. Mean bioavailability of dihydroergotamine mesylate is 32% to 40% after intranasal administration relative to injectable administration.  Tmax after intranasal administration is approximately 0.5 hours.

Avoid dihydroergotamine use during pregnancy. Dihydroergotamine possesses oxytocic properties. Available data indicate an increased risk of preterm delivery with dihydroergotamine use during pregnancy. Data collected over decades have shown no increased risk of major birth defects or miscarriage with use of dihydroergotamine during pregnancy. In animal studies, adverse effects on embryofetal development were observed after administration of dihydroergotamine during pregnancy (decreased fetal body weight and/or skeletal ossification) in rats and rabbits or during pregnancy and lactation (decreased body weight and impaired reproductive function in the offspring) in rats at doses less than those used clinically and which were not associated with maternal toxicity. [52524]

Because of the potential for reduced milk supply and serious adverse events in the breast-fed infant, advise patients against breast-feeding during treatment with dihydroergotamine and for 3 days after the last dose. Breast milk supply during this time should be pumped and discarded. There are no data on the presence of dihydroergotamine in human milk; however, ergotamine, a related drug, is present in human milk. There are reports of diarrhea, vomiting, weak pulse, and unstable blood pressure in breast-fed infants exposed to ergotamine. Dihydroergotamine may reduce milk supply because it may decrease prolactin concentrations. [52524] As a possible alternative, previous American Academy of Pediatrics (AAP) recommendations considered sumatriptan, a serotonin receptor agonist indicated for the treatment of migraines, as usually compatible with breast-feeding.[27500]