Ergoloid Mesylates

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 1 mg

Pharmacology

Mechanism of Action

Ergoloid mesylates do not have the vasoconstrictor effects of the natural ergot alkaloids; exact mechanism in dementia is unknown; originally classed as peripheral and cerebral vasodilator, now considered a "metabolic enhancer"; there is no specific evidence that clearly establishes the mechanism by which ergoloid mesylate preparations produce mental effects, nor is there conclusive evidence that the drug particularly affects cerebral arteriosclerosis or cerebrovascular insufficiency.

Pharmacokinetics/Pharmacodynamics

Absorption

Rapid yet incomplete

Metabolism

Hepatic, including first-pass metabolism

Time to Peak

Serum: 1.5 to 3 hours

Half-Life Elimination

Serum: ~2.6 to 5.1 hours

Use: Labeled Indications

Mental capacity decline: Treatment of signs and symptoms of an idiopathic decline in mental capacity.

Note: Individuals who do respond come from groups of patients who would be considered clinically to suffer from some ill-defined process related to aging or to have some underlying dementing condition (ie, primary progressive dementia, Alzheimer dementia, senile onset, multi-infarct dementia).

Contraindications

Hypersensitivity to ergoloid mesylates, ergot, or any component of the formulation; acute or chronic psychosis; concurrent use with potent inhibitors of cytochrome P450 (CYP-450) 3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics).

Canadian labeling: Additional contraindications (not in US labeling): Severe bradycardia; severe hypotension.

Documentation of allergenic cross-reactivity for ergot alkaloids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Mental capacity decline: Oral: 1 mg 3 times daily; results may not be observed until 3 to 4 weeks.

Dosing: Geriatric

Avoid use (Beers Criteria [AGS 2019]).

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Antihepaciviral Combination Products: May increase the serum concentration of Ergot Derivatives. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives. Consider therapy modification

Chloroprocaine: May enhance the hypertensive effect of Ergot Derivatives. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Itraconazole: May increase the serum concentration of Ergoloid Mesylates. Avoid combination

Ketoconazole (Systemic): May increase the serum concentration of Ergoloid Mesylates. Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Letermovir: May increase the serum concentration of Ergot Derivatives. Avoid combination

Lorcaserin: May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Avoid combination

Macrolide Antibiotics: May increase the serum concentration of Ergot Derivatives. Cabergoline and Clarithromycin may interact, see specific monograph for full details. Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Nefazodone: Ergot Derivatives may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nitroglycerin: Ergot Derivatives may diminish the vasodilatory effect of Nitroglycerin. This is of particular concern in patients being treated for angina. Nitroglycerin may increase the serum concentration of Ergot Derivatives. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Posaconazole: May increase the serum concentration of Ergoloid Mesylates. Avoid combination

Protease Inhibitors: May increase the serum concentration of Ergot Derivatives. Avoid combination

Reboxetine: May enhance the hypertensive effect of Ergot Derivatives. Monitor therapy

Roxithromycin: May increase the serum concentration of Ergot Derivatives. Avoid combination

Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nefazodone. Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): Ergot Derivatives may enhance the vasoconstricting effect of Serotonin 5-HT1D Receptor Agonists (Triptans). Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the vasoconstricting effect of Ergot Derivatives. Avoid combination

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Voriconazole: May increase the serum concentration of Ergoloid Mesylates. Avoid combination

Adverse Reactions

Frequency not defined. Adverse effects are minimal.

Cardiovascular: Bradycardia, flushing, orthostatic hypotension

Dermatologic: Skin rash

Gastrointestinal: Gastrointestinal distress (sublingual administration), nausea (sublingual administration; transient)

Local: Local irritation (sublingual administration)

Ophthalmic: Blurred vision

Respiratory: Nasal congestion

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac valvular fibrosis: Ergot alkaloids have been associated with fibrotic valve thickening (eg, aortic, mitral, tricuspid); usually associated with long-term, chronic use.
• Pleural/retroperitoneal fibrosis: Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use.

Concurrent drug therapy issues:

• Drug-drug interactions: Additional potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult Drug Interactions for more detailed information.

Other warnings/precautions:

• Appropriate use: Careful diagnosis should be attempted before prescribing. Because target symptoms are of unknown etiology, exclude potentially reversible and treatable conditions; particular care should be taken to exclude delirium and dementiform illness secondary to systemic disease, primary neurological disease, or primary disturbance of mood.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience abdominal pain. Have patient report immediately to prescriber severe nausea or severe vomiting (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.