dihydroergotamine intranasal

Action and Spectrum

Actions and Spectrum: 

Action: 

Vasoconstriction: Drug acts as a potent vasoconstrictor, mainly targeting the cranial blood vessels. It binds to and activates serotonin receptors (5-HT1B/1D) present on smooth muscle cells, leading to the constriction of blood vessels in the brain. This action helps reduce the dilation and inflammation of blood vessels during a migraine attack. 

Inhibition of neurogenic inflammation: The drug additionally hinders the secretion of neuropeptides, including substance P and calcitonin gene-related peptide (CGRP), which play a role in transmitting pain signals and initiating neurogenic inflammation. By suppressing the release of these inflammatory mediators, DHE helps alleviate migraines’ symptoms. 

Spectrum:  

Migraine with or without aura: Drug can be used to treat migraines with or without the presence of an aura. An aura refers to a set of neurological symptoms, such as visual disturbances or tingling sensations, that some individuals experience before the onset of a migraine attack. 

Acute migraine attacks: Drug is primarily employed for the acute treatment of migraines. It is often used when other medications, such as triptans, are contraindicated or ineffective. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Rhinitis (26%) 

1-10% 

Stiffness (1%) 

Dry mouth (1%) 

Asthenia (1%) 

Nausea (10%) 

Altered taste (8%) 

Application site reactions (6%) 

Vomiting (4%) 

Somnolence (3%) 

Paraesthesia (2%) 

Pharyngitis (3%) 

Diarrhea (2%) 

Sinusitis (1%) 

Hot flashes (1%) 

Fatigue (1%) 

Asthenia (1%) 

Black Box Warning

Black Box Warning:  

The concurrent use of dihydroergotamine with potent CYP3A4 inhibitors cause fatal peripheral ischemia 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Drug is contraindicated in individuals who have a known hypersensitivity or allergy to dihydroergotamine or any of its components.  

Ischemic heart disease: Drug can cause vasoconstriction (narrowing of blood vessels), which can affect blood flow to the heart. It is contraindicated in patients with a history of ischemic heart disease, including angina. 

Uncontrolled hypertension: Drug can elevate blood pressure due to its vasoconstrictive effects. It is contraindicated in patients with uncontrolled high blood pressure (hypertension) or severe hypertension, as it may worsen the condition and increase the risk of cardiovascular events. 

Peripheral vascular disease: Drug can constrict blood vessels not only in the brain but also in other parts of the body. It is contraindicated in individuals with peripheral vascular disease, such as peripheral arterial disease, as it may further compromise blood flow to the extremities. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: x 

Lactation:  Excreted into human milk is known will inhibit prolactin, contraindicated. 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

dihydroergotamine (DHE) is a medication used in the treatment of migraine headaches. When administered intranasally, DHE is absorbed through the nasal mucosa and exerts its pharmacological effects. 

Pharmacodynamics:  

dihydroergotamine is an ergot alkaloid and acts as a potent agonist at various serotonin (5-HT) receptor subtypes, particularly 5-HT1B, 5-HT1D, and 5-HT1F receptors. Activation of these receptors leads to vasoconstriction of cranial blood vessels and inhibition of neurogenic inflammation, thereby reducing the severity of migraine attacks.   

Pharmacokinetics: 

Absorption 

Drug is absorbed through the nasal mucosa after intranasal administration. The absorption rate is relatively rapid, leading to a quicker onset of action compared to other formulations.  

Distribution 

After absorption, dihydroergotamine is distributed throughout the body via the bloodstream. It readily crosses the blood-brain barrier, allowing it to exert its effects on the central nervous system. The drug’s distribution may be influenced by its binding to plasma proteins. 

Metabolism 

Drug undergoes extensive metabolism in the liver. The primary metabolic pathway involves enzymatic oxidation, primarily by the cytochrome P450 enzyme system.  

Excretion and Elimination 

The metabolites of dihydroergotamine are primarily excreted in the urine, with a small portion excreted in the feces. The elimination half-life of dihydroergotamine is relatively short, typically ranging from 2 to 3 hours. The exact rate of excretion and elimination may vary depending on factors such as individual patient characteristics, dose, and formulation. 

Adminstartion

Administration:  

Insert the nozzle gently into one nostril, closing the other nostril by applying light pressure with your finger. Avoid blocking the nostril completely, as this may impede the absorption of the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dihydroergotamine intranasal 

Why do we use dihydroergotamine intranasal?  

Migraine treatment: The drug is commonly recommended for the immediate management of migraines, both with and without aura. Its efficacy lies in alleviating moderate to severe migraine episodes through the constriction of cerebral blood vessels and the reduction of inflammation. 

Cluster headache treatment: Drug intranasal is also used in the treatment of cluster headaches, a type of severe headache that occurs in cyclical patterns. It can help alleviate the intense pain associated with cluster headaches and reduce the frequency and duration of these episodes. 

Acute headache relief: Drug intranasal may be used to provide immediate relief for acute headaches, including tension headaches and certain vascular headaches, by reducing blood vessel dilation and inflammation. 

Prophylaxis: In certain situations, medications can be employed as a proactive approach to diminish the occurrence and severity of recurrent migraines or cluster headaches.