Desloratadine

Desloratadine is a Second generation antihistamines, selective H1-receptor antagonists belonging to Antihistamines

Desloratadine is used in the treatment of Allergic rhinitis and Urticaria, chronic spontaneous. It is also used to treat Angioedema, acute allergic or recurrent idiopathic; Urticaria, new onset; Urticaria, nonsteroidal anti-inflammatory drug associated (prophylaxis) and allergic reaction.

Desloratadine is rapidly absorbed after oral administration and reaches peak plasma concentrations in about 3 hours. It is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 70%. Food does not affect the absorption of desloratadine. Desloratadine is highly protein-bound (about 83%) to plasma proteins such as albumin and alpha-1-acid glycoprotein. The volume of distribution of desloratadine is about 20 L/kg, indicating that it is widely distributed throughout the body. Desloratadine is extensively metabolized in the liver by the cytochrome P450 enzyme system, primarily by CYP3A4 and CYP2D6. The major metabolite of desloratadine is 3-hydroxydesloratadine, which is also active and has similar pharmacological properties as the parent drug. Desloratadine has a half-life of about 27 hours, while the half-life of 3-hydroxydesloratadine is about 36 hours. Desloratadine and its metabolites are eliminated mainly in the urine (about 87%) and feces (about 12%). Less than 2% of the drug is excreted unchanged in the urine. The elimination half-life of desloratadine is about 27 hours, while the half-life of 3-hydroxydesloratadine is about 36 hours.

The onset of action of desloratadine was Within 1 hour.

The Duration of time for Desloratadine was within 24 hours.

The Tmax of Desloratadine is approximately 3 hours after oral administration.

The average Cmax of desloratadine after a single oral dose of 5 mg is approximately 3.4 ng/mL.

Desloratadine shows common side effects like Headache Dry mouth Fatigue Somnolence (drowsiness) Nausea Pharyngitis (sore throat) Myalgia (muscle pain) Dysmenorrhea (menstrual cramps) Insomnia (difficulty sleeping) Diarrhea

Desloratadine is available in the form of oral solution and tablets

Desloratadine is available in India, Germany, Canada, Italy, USA

Desloratadine competes with free histamine for binding at H₁-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine.

Desloratadine is available in the form of oral solution and tablets.

Desloratadine is used in the treatment of Allergic rhinitis and Urticaria, chronic spontaneous. It is also used to treat Angioedema, acute allergic or recurrent idiopathic; Urticaria, new onset; Urticaria, nonsteroidal anti-inflammatory drug associated (prophylaxis) and allergic reaction.

Desloratadine is a second generation, tricyclic antihistamine that which has a selective and peripheral H1-antagonist action. It is the active descarboethoxy metabolite of loratidine (a second generation histamine). Desloratidine has a long-lasting effect and does not cause drowsiness because it does not readily enter the central nervous system.

Desloratadine is approved for use in the following clinical indications

Allergic rhinitis: Relief of nasal and non-nasal symptoms of seasonal (SAR) and perennial (PAR) allergic rhinitis

Urticaria, chronic spontaneous: Symptomatic relief of pruritus, reduction in number of hives, and reduction in size of hives associated with chronic spontaneous urticaria.

Although not approved there have been certain off label uses documented for Desloratadine which includes:

Angioedema, acute allergic or recurrent idiopathic; Urticaria, new onset; Urticaria, nonsteroidal anti-inflammatory drug associated (prophylaxis) and allergic reaction.

Oral

Allergic rhinitis, Urticaria

• Adult: 5 mg once daily. Patients with intermittent allergic rhinitis must be managed according to the evaluation of disease history, treatment may be discontinued after the symptoms are resolved and reinitiated upon reappearance; in case of persistent allergic rhinitis, continuous treatment may be considered during the periods of allergen exposure. Treatment recommendations may vary among countries and individual products
• Child: 1-5 years As oral solution and tablets or syrup: 1.25 mg once daily; 6-11 years As or dispersible tab, oral solution and tablets or syrup: 2.5 mg once daily; ≥12 years Same as adult dose. Treatment or dosage recommendations may vary among countries and individual products.

Desloratadine is available in various strengths as 2.5 mg, 5 mg, 0.5 mg/mL.

Desloratadine is available in the form of oral solution and tablets.

Dosage Adjustment in Kidney Patient

• Moderate to severe impairment: No dosage adjustment necessary; use with caution in severe impairment. Although the US manufacturer’s labeling recommends a dose reduction to 5 mg every other day in patients with mild to severe renal impairment, the increased exposure (C_max and AUC) observed in single- and multiple-dose pharmacokinetic studies is not considered clinically relevant
• Hemodialysis: Poorly dialyzable: No dosage adjustment necessary; use with caution. Although the US manufacturer’s labeling recommends a dose reduction to 5 mg every other day in patients on dialysis, the increased exposure (C_max and AUC) observed in single- and multiple-dose pharmacokinetic studies is not considered clinically relevant .

Dosage Adjustment for Pediatric Patients

• Perennial allergic rhinitis:

Oral:

Infants 6 to ≤11 months: 1 mg once daily.

Children ≤5 years: 1.25 mg once daily.

Children 6 to ≤11 years: 2.5 mg once daily.

Children ≥12 years and Adolescents: 5 mg once daily.

• Seasonal allergic rhinitis:

Oral:

Children 2 to ≤5 years: 1.25 mg once daily.

Children 6 to ≤11 years: 2.5 mg once daily.

Children ≥12 years and Adolescents: 5 mg once daily.

• Urticaria, chronic idiopathic:

Oral:

Infants 6 to ≤11 months: 1 mg once daily.

Children ≤5 years: 1.25 mg once daily.

Children 6 to ≤11 years: 2.5 mg once daily.

Children ≥12 years and Adolescents: 5 mg once daily.

Hypersensitivity to desloratadine, loratadine, or any component of the formulation.

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions (including anaphylaxis) have been reported with use; discontinue therapy immediately with signs/symptoms of hypersensitivity.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with severe hepatic impairment.

• Renal impairment: Use with caution in patients with severe renal impairment.

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Slow metabolizers: Use with caution in patients known to be slow metabolizers of desloratadine (incidence of side effects may be increased).

High-fat meal may decrease the rate but not the extent of absorption. Management: May administer with meals.

• Common Adverse effects:

Headache Dry mouth Fatigue Somnolence (drowsiness) Nausea Pharyngitis (sore throat) Myalgia (muscle pain) Dysmenorrhea (menstrual cramps) Insomnia (difficulty sleeping) Diarrhea

• Less Common Adverse effects:

Severe allergic reactions such as difficulty in breathing, shortness of breath, wheezing, itching, hives and swelling of the face, lips, tongue or other parts of the body and rash • Fits (seizures)

• Liver disease (nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, light coloured bowel motions, dark coloured urine)

• Rare Common Adverse effects:

Aggression Depression Hallucinations Abnormal thinking and behavior Abnormal liver function tests Pancreatitis Acute generalized exanthematous pustulosis (a severe skin reaction)

May increase plasma concentrations with ketoconazole, erythromycin, azithromycin, fluoxetine, and cimetidine.

The common side effects of Desloratadine include the following Headache Dry mouth Fatigue Somnolence (drowsiness) Nausea Pharyngitis (sore throat) Myalgia (muscle pain) Dysmenorrhea (menstrual cramps) Insomnia (difficulty sleeping) Diarrhea.

Pharmacodynamic

Desloratadine is a long-acting second-generation H₁-receptor antagonist which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergies. Desloratadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Desloratadine does not enter the brain from the blood and, therefore, does not cause drowsiness.

Pharmacokinetics

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Desloratadine?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/