Desloratadine
1. Drug Name
Generic Name: Desloratadine
Brand Names: Clarinex, Aerius, Desalex
2. Drug Classification
Class: Antihistamine
Subclass: Second-generation H1-receptor antagonist
3. Mechanism of Action
Histamine Blockade: Desloratadine is a selective peripheral H1 receptor antagonist. Histamine is a key mediator in allergic responses, acting on H1 receptors to cause symptoms such as itching, redness, and swelling. By blocking these receptors, desloratadine reduces allergic symptoms like rhinitis, urticaria (hives), and itching.
Non-Sedating: Unlike first-generation antihistamines, desloratadine is less likely to cross the blood-brain barrier, which minimizes central nervous system (CNS) effects such as drowsiness.
Anti-inflammatory Effects: In addition to histamine antagonism, desloratadine has mild anti-inflammatory effects, which contribute to the reduction of allergic inflammation.
4. Pharmacokinetics
Absorption:
Bioavailability: Desloratadine has a high bioavailability of approximately 83%, with peak plasma concentrations reached within 3 hours of oral administration.
Food Effects: The absorption of desloratadine is not significantly affected by food, allowing it to be taken with or without meals.
Distribution:
Volume of Distribution (Vd): Desloratadine has a volume of distribution of approximately 12 L/kg, indicating widespread distribution in body tissues.
Protein Binding: Desloratadine is highly protein-bound (approximately 83-87%), primarily to serum albumin.
Metabolism:
Desloratadine is extensively metabolized in the liver to its active metabolite, 3-hydroxy-desloratadine, primarily via the cytochrome P450 enzymes CYP3A4 and CYP2D6.
It has a minimal potential for drug-drug interactions due to its lack of significant inhibition of cytochrome P450 enzymes.
Excretion:
Half-life (t½): Desloratadine has a long elimination half-life of approximately 27 hours, which supports once-daily dosing.
Excretion: Desloratadine and its metabolites are primarily excreted in the urine (approximately 70%) and to a lesser extent in feces (about 8%).
5. Indications
Primary Indications:
Allergic Rhinitis: Desloratadine is indicated for the treatment of seasonal and perennial allergic rhinitis, reducing symptoms such as sneezing, runny nose, itching, and nasal congestion.
Chronic Urticaria: Desloratadine is used for the management of chronic idiopathic urticaria (hives), relieving symptoms such as itching and the appearance of welts or hives on the skin.
Off-Label Uses:
Angioedema: Desloratadine may be used off-label for the management of angioedema, reducing the severity of swelling and inflammation.
Special Populations:
Pediatrics: Approved for use in children aged 6 months and older for allergic rhinitis and chronic urticaria, with appropriate dose adjustments.
Geriatrics: Generally safe in elderly patients, but caution should be used in those with impaired renal function.
6. Dosage and Administration
Adult Dosing:
Allergic Rhinitis:
Oral (Tablet or Syrup): 5 mg once daily.
Chronic Urticaria:
Oral (Tablet or Syrup): 5 mg once daily.
Pediatric Dosing:
Allergic Rhinitis:
Children aged 6 months to 5 years: 1.25 mg once daily.
Children aged 6 to 11 years: 2.5 mg once daily.
Children aged 12 years and older: 5 mg once daily.
Chronic Urticaria:
Children aged 6 months to 5 years: 1.25 mg once daily.
Children aged 6 to 11 years: 2.5 mg once daily.
Children aged 12 years and older: 5 mg once daily.
Renal or Hepatic Impairment:
No dose adjustment is necessary in patients with mild to moderate hepatic impairment. However, patients with severe hepatic impairment should be closely monitored.
In patients with renal impairment (creatinine clearance <30 mL/min), a dose reduction may be necessary.
7. Contraindications
Absolute Contraindications:
Hypersensitivity to desloratadine, loratadine, or any excipient in the formulation.
Relative Contraindications:
Severe Renal or Hepatic Impairment: Although dose adjustments are made, caution is advised in patients with significant renal or hepatic dysfunction.
8. Warnings and Precautions
CNS Depression: Although desloratadine is less sedating than first-generation antihistamines, rare instances of drowsiness or dizziness may occur. Patients should be advised not to engage in activities requiring alertness (e.g., driving or operating heavy machinery) if these side effects occur.
Renal or Hepatic Dysfunction: Desloratadine should be used with caution in patients with severe renal or hepatic impairment.
Pregnancy: Desloratadine is classified as a Category C drug during pregnancy. It should be used only when the potential benefits outweigh the risks.
Lactation: Desloratadine is excreted in breast milk in small amounts. Caution is advised when administering desloratadine to breastfeeding mothers.
9. Adverse Effects
Common Adverse Effects:
Headache: The most frequently reported side effect.
Dry Mouth: Mild and transient in most cases.
Fatigue: Occasional and usually resolves with continued use.
Less Common but Clinically Significant:
Dizziness: Rare, but may occur in some individuals.
Palpitations: An occasional side effect, typically mild.
Rare/Serious:
Severe Allergic Reactions: Rare, including anaphylaxis.
Cardiovascular Effects: Tachycardia and QT interval prolongation have been rarely reported.
10. Drug Interactions
CYP450 Interactions: Desloratadine has minimal interaction with the cytochrome P450 system, making it less likely to interfere with other medications metabolized by these enzymes.
Alcohol: Although desloratadine is non-sedating, alcohol consumption should still be avoided or minimized as it can exacerbate CNS depression.
Other Antihistamines: Using other antihistamines in combination with desloratadine may increase the risk of adverse effects such as dry mouth, drowsiness, and dizziness.
11. Clinical Pharmacology
Pharmacodynamics: Desloratadine selectively binds to H1 receptors, inhibiting the action of histamine. This results in a reduction in allergy symptoms such as sneezing, itching, and rhinorrhea. It also has mild anti-inflammatory effects, which help reduce symptoms of allergic rhinitis and urticaria.
Additional Effects: Desloratadine’s ability to reduce inflammation makes it effective in conditions like chronic urticaria, where inflammation plays a key role in the formation of hives.
12. Special Populations
Pregnancy: Category C. Limited data on safety in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.
Lactation: Desloratadine is excreted in breast milk in small amounts. Use with caution in breastfeeding mothers.
Pediatrics: Safe for use in children aged 6 months and older with appropriate dosing.
Geriatrics: No specific dose adjustments are required for elderly patients, but caution should be exercised, particularly in those with renal or hepatic dysfunction.
13. Therapeutic Uses
Allergic Rhinitis: Desloratadine is used as a long-term treatment for the relief of allergic rhinitis symptoms such as sneezing, nasal congestion, and itching.
Chronic Urticaria: It is used to treat chronic urticaria, reducing symptoms like itching and the development of hives.
Adjunctive Treatment for Allergies: Can be used in combination with other treatments for allergic conditions, including corticosteroids and nasal sprays.
14. Monitoring and Follow-Up
Symptom Control: Regular monitoring of symptom control in allergic rhinitis and urticaria.
Renal and Hepatic Function: In patients with renal or hepatic dysfunction, periodic assessments should be conducted.
Side Effects: Monitoring for signs of sedation, dizziness, or other CNS side effects, particularly when starting therapy.
15. Overdose Management
Symptoms of Overdose: Overdose symptoms may include headache, dry mouth, drowsiness, and tachycardia.
Management: There is no specific antidote for desloratadine overdose. Management is supportive, and gastric lavage or activated charcoal may be used if overdose occurs within a short time frame.
16. Patient Counseling Information
Administration: Instruct patients to take desloratadine once daily, with or without food.
Adverse Effects: Patients should be informed about the potential for mild side effects such as dry mouth or headache.
Monitoring: Advise patients to report any unusual symptoms such as dizziness or palpitations, particularly when starting therapy.
Avoid Alcohol: Patients should be advised to avoid alcohol, as it can increase the risk of CNS depression.