astemizole

Action and Spectrum

Actions and spectrum: 

Action: 

• astemizole was classified as a second-generation H1 receptor antagonist. It worked by blocking the effects of histamine, a chemical that the body releases during allergic reactions. By blocking histamine’s action on H1 receptors, astemizole could alleviate allergy symptoms such as sneezing, runny nose, itching, and watery eyes. 

Spectrum: 

• Allergic Rhinitis: It was used to relieve symptoms of seasonal and perennial allergic rhinitis, commonly known as hay fever. 
• Urticaria (Hives): astemizole was used to treat chronic idiopathic urticaria, a skin condition characterized by the presence of hives and itching without a known cause. 
• Allergic Conjunctivitis: It was also used to alleviate symptoms of allergic conjunctivitis, which includes redness, itching, and tearing of the eyes due to allergies. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Abnormal heart rhythm 

Hypotension 

Palpitations 

dizziness 

headache 

increased appetite   

nervousness 

Drowsiness 

fatigue 

Nausea 

abdominal pain 

diarrhea 

Dry mouth 

Joint pain 

Black Box Warning

Black Box Warning: 

The black box warning for astemizole was a crucial safety advisory due to its potential to cause life-threatening cardiac arrhythmias, including torsades de pointes. This led to its withdrawal from the market in many countries.

The warning alerted healthcare providers and patients to the serious risks associated with this antihistamine, particularly in cases of overdose or interactions with other medications prolonging the QT interval. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known Allergy: Individuals with a known allergy or hypersensitivity to astemizole or any of its components should not use this medication. 
• Torsades de Pointes: astemizole was contraindicated in individuals with a history of, or those at risk of developing, torsades de pointes, a specific type of potentially life-threatening heart rhythm disorder. 
• Liver Dysfunction: Individuals with severe liver dysfunction were often advised to avoid astemizole, as the medication is metabolized in the liver and may accumulate in the bloodstream in the presence of liver impairment. 
• Renal Impairment: Individuals with severe kidney impairment may have been at risk of increased blood levels of astemizole due to reduced elimination. Adjustments to the dosage or alternative medications may have been considered in these cases.  

Caution: 

• Elderly Population: Elderly individuals may be more sensitive to the effects of astemizole. Caution was advised, and lower doses may have been considered in this population. 
• Pregnancy and Breastfeeding: Due to safety concerns, it was recommended that pregnant and breastfeeding women avoid using astemizole. Alternative medications for managing allergy symptoms were typically preferred. 
• Pediatric Use: The safety and efficacy of astemizole in children, especially in infants and young children, may not have been well established. Caution and careful monitoring may have been recommended when considering its use in pediatric populations. 
• Heart Conditions: People with preexisting heart conditions, especially those at risk of arrhythmias, were advised not to use astemizole. This included individuals with a history of heart rhythm disorders, heart disease, or conditions that may prolong the QT interval. 

Comorbidities: 

• Asthma: Many individuals with allergies, which astemizole was designed to treat, also have asthma. Allergies can trigger or exacerbate asthma symptoms, and the management of both conditions may need to be coordinated. 
• Rhinitis (Nasal Inflammation): Allergic rhinitis often coexists with other allergic conditions. Symptoms of rhinitis, such as a runny or stuffy nose, sneezing, and nasal congestion, are common comorbidities with allergies. 
• Eczema: It is the chronic skin condition that is sometimes associated with allergies. People with atopic dermatitis may experience itching and skin inflammation, and the use of antihistamines like astemizole might be considered to alleviate symptoms. 
• Chronic Sinusitis: Chronic sinusitis may be comorbid with allergies. Allergies can contribute to sinus inflammation and lead to chronic sinusitis in some individuals. 
• Allergic Conjunctivitis: Allergic conjunctivitis is an eye condition characterized by redness, itching, and tearing of the eyes due to allergies. It often coexists with other allergy-related conditions. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: C 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• 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: 

astemizole was a second-generation antihistamine with a pharmacological profile aimed at alleviating allergy symptoms. It worked by blocking the effects of histamine, a chemical released during allergic reactions, by selectively binding to histamine H1 receptors. This action inhibited histamine’s role in producing symptoms such as sneezing, itching, and runny nose.

astemizole also had the advantage of a longer duration of action, which allowed for once-daily dosing. However, it was withdrawn from the market in many countries due to concerns about its potential to cause serious cardiac arrhythmias, particularly torsades de pointes. This safety issue led to the discontinuation of astemizole, and safer alternatives are now commonly used for allergy management.  

Pharmacodynamics: 

• Histamine Receptor Antagonism: astemizole acted as a competitive antagonist at histamine H1 receptors. These receptors mediate the effects of histamine in allergic reactions. By binding to these receptors without activating them, astemizole effectively blocked the actions of histamine. 
• Inhibition of Histamine Effects: By blocking histamine H1 receptors, astemizole reduced the physiological responses associated with histamine release. This included the relief of symptoms like sneezing, itching, runny nose, and watery eyes, commonly seen in allergic rhinitis and urticaria (hives). 
• Selective Binding: astemizole was considered a second-generation antihistamine because it was designed to be more selective for histamine H1 receptors, minimizing its binding to other receptors. This selectivity reduced the potential for side effects commonly seen with first-generation antihistamines, such as drowsiness and sedation.

Pharmacokinetics: 

Absorption 

astemizole was well absorbed after oral administration. However, its absorption was affected by food, which could reduce the rate and extent of absorption. It was recommended to take astemizole on an empty stomach for optimal absorption. 

Distribution 

Once absorbed, astemizole was distributed throughout the body, including to the tissues. It crossed the blood-brain barrier and cause central nervous system side effects, although it was designed to be less sedating than first-generation antihistamines. 

Metabolism 

astemizole is metabolized in the liver by the cytochrome P450 (CYP) enzyme system, primarily by CYP3A4 and CYP2D6 enzymes. During this metabolism, it is converted into its active metabolite, desmethylastemizole. However, both astemizole and desmethylastemizole could accumulate in the bloodstream, potentially leading to safety concerns. 

Elimination and excretion 

The elimination of astemizole and its metabolites occurred via hepatic clearance, with a small fraction excreted in the urine. It had a long half-life, contributing to its extended duration of action. 

Adminstartion

Administration: 

• Dosage: The dosage of astemizole was determined by a healthcare provider based on the individual’s age, weight, and the specific condition being treated. It was typically taken once a day. 
• Time of Administration: astemizole was often recommended to be taken on an empty stomach. This meant taking it at least one hour before or two hours after a meal to optimize absorption. However, the specific instructions could vary depending on the product, so it is essential to follow the label or healthcare provider’s guidance. 
• Duration of Use: The duration of astemizole use was typically determined by the treating healthcare provider. It was often used for the relief of allergic symptoms and conditions, but the duration depended on the specific circumstances. In many cases, it was used for the duration of the allergy season or as directed by the provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: astemizole 

Pronounced: (a stem’ mi zole)  

Why do we use astemizole? 

astemizole was used to relieve symptoms of allergic rhinitis. This condition is characterized by sneezing, runny or itchy nose, and other allergy-related nasal symptoms. astemizole was used to treat chronic idiopathic urticaria, a skin condition characterized by the presence of hives and itching without a known cause. It was used to alleviate symptoms of allergic conjunctivitis, which includes redness, itching, and tearing of the eyes due to allergies. astemizole could also be used to relieve itching associated with various allergic skin conditions.