Ergoloid mesylates contain a combination of synthetic derivatives of naturally occurring ergot alkaloids (dihydroergocornine, dihydroergocristine, and dihydroergocryptine). Ergoloid mesylates are approved for the symptomatic management of various dementias including vascular dementia, Alzheimer's disease, and primary progressive dementia. At therapeutic doses, ergoloid mesylates have few side effects and lack the vasoconstrictor properties of the natural ergot alkaloids. Despite a favorable safety profile, the role of ergoloid mesylates in the management of various dementias remains controversial. The majority of studies evaluating ergoloid mesylates for vascular dementia were conducted prior to the development of standardized diagnostic criteria and study results have been inconsistent. Practice guidelines do not support the use of ergoloid mesylates in the treatment of Alzheimer's disease.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Oral tablets: May administer at meals or with food or milk to help limit upset stomach.
Gastrointestinal adverse effects which may frequently occur during therapy with ergoloid mesylates and include nausea, vomiting, stomach cramps, decreased appetite (anorexia), and transient dyspepsia. Sublingual irritation (soreness under the tongue) has been reported following administration of sublingual tablets.
At therapeutic doses, ergoloid mesylates (dihydrogenated ergot alkaloids) have few side effects and lack the vasoconstrictor properties of the natural ergot alkaloids. However, ergoloid mesylates have been associated with cardiovascular adverse effects including sinus bradycardia, hypotension, and orthostatic hypotension. Dizziness, headache, or syncope may accompany hypotensive effects. Blood pressure and heart rate should be monitored prior to initiating therapy and at periodic intervals during therapy. If significant bradycardia or hypotension occurs, ergoloid mesylates should be discontinued.
According to the manufacturer, therapeutic doses of ergoloid mesylates (dihydrogenated ergot alkaloids) have few side effects and lack certain properties of the natural ergot alkaloids. However, blurred vision, nasal congestion, rash (unspecified), and flushing may occur.
Careful diagnosis should be performed prior to prescribing ergoloid mesylates to rule out reversible or treatable underlying conditions which contribute to symptoms of dementia. Ergoloid mesylates are contraindicated in patients with sensitivity to ergoloid mesylates or in patients with known ergot alkaloid hypersensitivity. Ergoloid mesylates are also contraindicated in patients with acute or chronic psychosis, regardless of etiology; dopamine agonist activity may exacerbate pre-existing psychosis.
Ergoloid mesylates should be used with caution in patients with bradycardia or hypotension, since these conditions can be exacerbated during ergoloid mesylate therapy. Heart rate and blood pressure should be monitored during therapy; if significant bradycardia or hypotension occurs ergoloid mesylates should be discontinued.
Ergoloid mesylates are extensively metabolized by the liver. Therefore, ergoloid mesylates should be used with caution in patients with hepatic disease, since hepatic impairment could limit drug elimination mechanisms.
Although specific data are lacking for ergoloid mesylates, ergot derivatives should generally be avoided during breast-feeding. There are no specific studies evaluating the safety of ergoloid mesylates in breast-feeding; however, other ergot derivatives such as ergotamine are excreted in breast milk and may cause symptoms indicative of ergot toxicity including vomiting, diarrhea, seizures, weak pulse, and unstable blood pressure in nursing infants. Ergotamine is classified by the American Academy of Pediatrics (AAP) as a drug that has been associated with significant effects on some nursing infants and should be given to nursing mothers with caution. Therapeutic doses of ergoloid mesylates can decrease prolactin levels, and thus, interference with proper lactation is possible. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Although specific data are lacking for ergoloid mesylates, natural ergot alkaloids are considered contraindicated (pregnancy risk category X) during pregnancy due to their oxytocic and uterine stimulant properties. Ergot alkaloids are also generally avoided during labor and obstetric delivery due to their oxytocic effect. Ergot alkaloids are not established human teratogens; however, limited data indicate that in utero exposure to ergotamine during pregnancy may be associated with fetal malformations, primarily consistent with ischemic injury. Because ergoloid mesylates preparations do not possess the vasoconstrictor properties of the natural ergot alkaloids, the fetal toxicity risk is unknown. Women of child-bearing potential should be counseled on the potential risks to the fetus should pregnancy occur during use of ergoloid mesylates.
In general, ergoloid mesylates dosing should be more cautious in geriatric patients, starting at the lower end of the dose range to account for differences in renal, hepatic, or cardiac systems as well as concomitant disease states and medications. The use of ergoloid mesylates in the therapy of dementia, including Alzheimer's disease and vascular dementia, is controversial; there is a lack of data to support efficacy. According to the Beers Criteria, ergoloid mesylates are considered a potentially inappropriate medication (PIM) for use in geriatric patients and should be avoided due to lack of established efficacy.
There is no established use of ergoloid mesylates in children or infants < 18 years of age.
For the symptomatic management of Alzheimer's disease, vascular dementia, or primary progressive dementia:
Oral dosage:
Adults: 1 mg PO 3 times per day. Clinical improvement may take 3 to 4 weeks after initiating therapy. Assess treatment benefits periodically. It is not known if there are patient traits that would usefully predict a positive response to ergoloid mesylates therapy. While doses up to 9 mg/day (3 mg PO 3 times per day) have been studied, statistically significant differences in effect at higher doses than the labeled dose have not been noted. The role of ergoloid mesylates in the management of dementia remains controversial. The majority of studies evaluating ergoloid mesylates for vascular dementia were conducted prior to the development of standardized diagnostic criteria and study results have been inconsistent. Practice guidelines do not support the use of ergoloid mesylates in the treatment of Alzheimer's disease.
Maximum Dosage Limits:
-Adults
3 mg/day PO is usual dose; doses up to 9 mg/day have been studied.
-Geriatric
3 mg/day PO is usual dose; doses up to 9 mg/day have been studied.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Not indicated.
Patients with Hepatic Impairment Dosing
No guidelines for dosage adjustment are available; use with caution in patients with hepatic disease as ergoloid mesylates are extensively metabolized in the liver.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
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.
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.
Amphetamine: (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.
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.
Amphetamine; Dextroamphetamine: (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.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and methylene blue. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
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.
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.
Citalopram: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
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: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Dextroamphetamine: (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.
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.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension.
Duloxetine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Erythromycin: (Moderate) Monitor for symptoms of dopamine excess and other ergoloid mesylates (co-dergocrine)-related adverse effects during concomitant use of erythromycin. Concomitant use has been observed to increase overall exposure of alpha-dihydroergocryptine (DHEC), one of the components of ergoloid mesylates, by 16.5-fold in a healthy volunteer drug interaction study. DHEC acts primarily as a dopamine agonist, however, ergoloid mesylates have a complex effect on the neurotransmitter system and the net clinical impact of this concentration change is unknown. Each 1 mg of ergoloid mesylates contains approximately 0.2 mg of DHEC. DHEC is a CYP3A substrate; erythromycin was studied at a dose of 500 mg every 8 hours and acted as a strong CYP3A inhibitor.
Escitalopram: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Fluoxetine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Fluvoxamine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and methylene blue. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Isoproterenol: (Contraindicated) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension. Ergot alkaloids exacerbate the effect of isoproterenol on increased cardiac output while producing peripheral vasoconstriction, resulting in increased blood pressure.
Levomilnacipran: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Linezolid: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and linezolid. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
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: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and methylene blue. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Methylene Blue: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and methylene blue. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Milnacipran: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Mirtazapine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and mirtazapine. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Nicardipine: (Major) Nicardipine is an inhibitor of CYP3A4 isoenzymes. Coadministration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates, such as ergoloid mesylates.
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.
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.
Olanzapine; Fluoxetine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Paroxetine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
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.
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.
Selective serotonin reuptake inhibitors: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Serotonin norepinephrine reuptake inhibitors: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a selective serotonin reuptake inhibitor (SSRI). Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
Venlafaxine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and a serotonin norepinephrine reuptake inhibitor. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Vilazodone: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and vilazodone. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
Vortioxetine: (Minor) Monitor for symptoms of serotonergic toxicity during concomitant use of ergoloid mesylates (co-dergocrine mesylate) and vortioxetine. Serotonin receptor agonist and antagonist activity has been observed with ergoloid mesylates. Concomitant use may increase the risk for serotonin syndrome in some patients.
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.
There is no specific evidence which clearly establishes the mechanism by which ergoloid mesylates preparations produce mental effects, nor is there conclusive evidence that the drug particularly affects cerebral arteriosclerosis or cerebrovascular insufficiency. Proposed mechanisms are largely based on animal in vitro data. Ergoloid mesylates are considered a cerebral metabolic enhancing agent; the proposed mechanism is improved oxygen uptake and improved neuronal cell metabolism, with potential normalization of depressed neurotransmitter levels. Ergoloid mesylates are associated with alpha-adrenergic blocking activity, and may act as agonists of serotonin and dopamine receptors. At therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids.
Ergoloid mesylates (dihydroergocornine, dihydroergocristine, and dihydroergocryptine) are administered orally. Ergoloid mesylates undergo significant (about 50%) first-pass hepatic metabolism. The mean half-life of ergoloid mesylates is about 3.5 hours (range 2.6 to 5.1 hours).
Affected Cytochrome P450 enzymes and drug transporters: None known.
-Route-Specific Pharmacokinetics
Oral Route
Ergoloid mesylates are rapidly absorbed from the gastrointestinal tract, but oral bioavailability is approximately 25%. Peak plasma concentrations occur within 1.5 to 3 hours. The finding of lower peak levels of ergoloid compared to the total drug-metabolite composite is consistent with a considerable first-pass liver metabolism, with less than 50% of the therapeutic moiety reaching the systemic circulation after oral administration. Oral tablet or solution dosage forms and sublingual dosage forms result in similar bioavailability. The clinical therapeutic effects of a particular dose may not be apparent for 3 to 4 weeks.
-Special Populations
Hepatic Impairment
Ergoloid mesylates are extensively metabolized in the liver.
Renal Impairment
No data are available but renal impairment is not expected to have a significant effect on ergoloid mesylate pharmacokinetics.