ergotamine

Action and Spectrum

Actions and Spectrum: 

ergotamine’s primary mechanism of action is through its binding to and activation of serotonin (5-HT) receptors, specifically the 5-HT1B and 5-HT1D subtypes. Activation of these receptors leads to vasoconstriction (narrowing of blood vessels) and inhibition of neurogenic inflammation, both contributing to relieving migraine headaches. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Abnormal heart valve findings  

Vascular spasm 

Vasoconstriction 

Angina 

Arrhythmia 

Tachycardia 

Rebound headache 

Abdominal pain 

Fatigue 

Numbness of extremities 

Paresthesia 

Pruritis 

Ergotism 

Possible gangrene 

Muscle weakness 

Visual disturbances 

Nausea 

Vomiting 

Black Box Warning

Black Box Warning: 

If administered with potent CYP3A4 inhibitors, it may cause life-threatening ischemia.

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity or Allergy: Individuals with known hypersensitivity or allergy to ergotamine should not use this medication. 
• Ischemic Heart Disease: ergotamine can cause vasoconstriction (narrowing of blood vessels), which may exacerbate ischemic heart conditions like angina or previous heart attacks. 
• Peripheral Vascular Disease: ergotamine’s vasoconstrictive effects may worsen conditions like peripheral artery disease. 
• Uncontrolled Hypertension: High blood pressure that is not well controlled may be aggravated by ergotamine. 
• Severe Liver or Kidney Disease: Impaired liver or kidney function can affect the metabolism and elimination of ergotamine, leading to potentially adverse effects. 
• Pregnancy and Breastfeeding: ergotamine is generally not recommended during pregnancy and breastfeeding. 

Cautions: 

• Drug Interactions: ergotamine can interact with various medications, including certain antifungal drugs, macrolide antibiotics, protease inhibitors, and others, leading to increased ergotamine levels and a higher risk of adverse effects. 
• Other Medical Conditions: Individuals with uncontrolled hypertension, renal impairment, liver impairment, or certain heart conditions may require cautious use of ergotamine. 
• Long-Term Use: Prolonged or frequent use of ergotamine can lead to rebound headaches or medication overuse, so it should be used as needed. 

Pregnancy / Lactation

Pregnancy consideration:  

It is contraindicated during pregnancy. 

Breastfeeding warnings:  

The drug gets excreted in the breast milk. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology

Pharmacology: 

ergotamine acts primarily by binding to and activating serotonin (5-HT) receptors, specifically the 5-HT1B and 5-HT1D subtypes. This leads to vasoconstriction (narrowing of blood vessels) and inhibition of neurogenic inflammation, contributing to the relief of migraine headaches. 

Pharmacodynamics: 

The pharmacodynamics of ergotamine involves understanding how the drug’s interactions with receptors and cellular pathways lead to its therapeutic effects. As mentioned earlier, ergotamine exerts its effects primarily by binding to 5-HT1B and 5-HT1D receptors, resulting in vasoconstriction and reducing the release of inflammatory neuropeptides. 

ergotamine also affects other receptors, such as dopamine and alpha-adrenergic receptors. Its interactions with these receptors may contribute to specific side effects and cautions associated with its use. 

Pharmacokinetics: 

Absorption 

ergotamine can be administered through various routes, including oral, sublingual, and rectal (suppository). After oral administration, ergotamine is rapidly absorbed from the gastrointestinal tract, but its bioavailability is relatively low due to extensive first-pass metabolism in the liver. 

Distribution 

After absorption, ergotamine is distributed throughout the body via the bloodstream. It readily crosses the blood-brain barrier, allowing it to exert its effects in the brain, where it acts on serotonin receptors to alleviate migraines. 

Metabolism 

ergotamine undergoes extensive metabolism in the liver. The primary enzyme in its metabolism is cytochrome P450 3A4 (CYP3A4). It is metabolized into several active and inactive metabolites. Some of the active metabolites also contribute to the drug’s vasoconstrictive effects. 

Elimination and Excretion 

The elimination of ergotamine and its metabolites occurs primarily through the urine, with a smaller portion being eliminated in the feces. The elimination half-life of ergotamine is relatively long, ranging from 2 to 3 hours. Due to this extended half-life, caution is required to avoid drug accumulation when repeated doses are taken closely together. 

Adminstartion

Administration: 

ergotamine is available in various formulations and is typically administered for the acute treatment of migraine headaches. The specific route and dosage of ergotamine may vary based on the formulation and individual patient factors. It is crucial to follow the healthcare professional’s instructions or the drug’s package insert for proper administration. 

Patient Information Leaflet

Patient information leaflet 

Generic Name:  ergotamine 

Pronounced: er-go-tah-meen 

Why do we use ergotamine? 

ergotamine is used for the acute treatment of migraine headaches and, to a lesser extent, for the treatment of cluster headaches. Its use is based on its pharmacological properties and historical effectiveness in managing inevitable headaches. It can also be used for menstrual hot flashes.