Usage
Rupatadine is prescribed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and urticaria (hives). It is a second-generation antihistamine. Rupatadine’s mechanism of action involves selectively antagonizing peripheral histamine H1 receptors. It also exhibits platelet-activating factor (PAF) antagonism, which may contribute to its anti-allergic effects.
Alternate Names
While “Rupatadine” is the internationally recognized generic name, it’s marketed under various brand names such as Rupall, Urtimed, and Rupafin.
How It Works
Pharmacodynamics: Rupatadine exerts its therapeutic effect by binding to and blocking peripheral H1 histamine receptors. This action inhibits the effects of histamine, a mediator released during allergic reactions, thus reducing symptoms like itching, sneezing, runny nose, and watery eyes. Additionally, its PAF antagonism may further suppress inflammatory responses associated with allergies.
Pharmacokinetics:
- Absorption: Rupatadine is well-absorbed after oral administration, reaching peak plasma concentration (Cmax) in approximately 4-5 hours. Food does not significantly affect its absorption.
- Metabolism: Rupatadine is extensively metabolized in the liver, primarily by the cytochrome P450 (CYP3A4) enzyme system. This results in several metabolites, including its major active metabolite, desloratadine.
- Elimination: Rupatadine and its metabolites are eliminated primarily through feces and to a lesser extent via urine, with a mean elimination half-life of around 6 hours.
Mode of Action: Rupatadine competitively binds to H1 receptors, preventing histamine from binding and triggering downstream allergic responses. At the cellular level, this inhibits histamine-mediated vasodilation, capillary permeability increase, and smooth muscle contraction.
Receptor Binding/Enzyme Inhibition: Rupatadine exhibits high selectivity for H1 receptors and does not significantly interact with other receptor types. It acts as a mild inhibitor of CYP3A4.
Elimination Pathways: Rupatadine is primarily eliminated through hepatic metabolism (CYP3A4) followed by biliary excretion. Renal excretion plays a minor role.
Dosage
Standard Dosage
Adults: 10 mg (one tablet) once daily, with or without food.
Children (2-11 years):
- 10 kg to <25 kg: 2.5 mg (2.5 mL of oral solution) once daily.
- ≥25 kg: 5 mg (5 mL of oral solution) once daily.
- <2 years: Not recommended due to lack of data.
- ≥12 years: Same as adult dose.
Special Cases:
- Elderly Patients: Use with caution as they may be more sensitive to side effects, especially QT prolongation. No specific dose adjustment is routinely recommended, but careful monitoring is advised.
- Patients with Renal Impairment: Not recommended due to lack of clinical experience.
- Patients with Hepatic Dysfunction: Not recommended due to lack of clinical experience.
- Patients with Comorbid Conditions: Use with caution in patients with known QT interval prolongation, uncorrected hypokalemia, or ongoing proarrhythmic conditions.
Clinical Use Cases
Rupatadine’s use is limited to the management of allergic rhinitis and urticaria. It is not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are not routinely recommended in elderly patients. However, close monitoring for adverse effects is necessary. No dose adjustments are established for patients with renal or hepatic impairment since the drug is not recommended in these populations.
Side Effects
Common Side Effects
- Somnolence (sleepiness)
- Headache
- Dizziness
- Dry mouth
- Fatigue
Rare but Serious Side Effects
- Hypersensitivity reactions (e.g., anaphylaxis, angioedema)
- QT prolongation
- Torsades de pointes
- Liver function abnormalities
Long-Term Effects
Limited data are available on long-term effects. Monitor for potential liver function changes with chronic use.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe hypersensitivity reactions (anaphylaxis, angioedema), QT interval prolongation, and torsades de pointes.
Contraindications
- Hypersensitivity to rupatadine.
- Known QT interval prolongation or congenital long QT syndrome.
- History of cardiac arrhythmias, particularly Torsades de pointes.
- Concurrent use of potent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin).
- Concomitant use of other QT-prolonging drugs.
- Severe renal impairment.
- Severe hepatic impairment.
- Galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (for tablets).
- Hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency (for oral solution).
Drug Interactions
- CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) should be avoided as it can significantly increase rupatadine plasma concentrations.
- QT-prolonging drugs: Concomitant use with other QT interval prolonging drugs is contraindicated due to the increased risk of torsades de pointes.
- CNS Depressants: Concomitant use with alcohol and other CNS depressants may enhance sedative effects.
- Grapefruit juice: Avoid concomitant use as it may increase rupatadine plasma levels.
- Statins: Monitor patients taking statins (e.g., simvastatin, lovastatin) as rupatadine may increase their plasma concentrations.
- Drugs with Narrow Therapeutic Index: Exercise caution with drugs like ciclosporin, tacrolimus, sirolimus, everolimus, and cisapride due to potential interaction.
Pregnancy and Breastfeeding
- Pregnancy: Limited data are available. Animal studies have not shown harm, but as a precaution, rupatadine use during pregnancy is generally avoided unless clearly needed.
- Breastfeeding: Rupatadine is excreted in animal milk. It is unknown if it is excreted in human breast milk. Use with caution during breastfeeding. A decision must be made whether to discontinue breastfeeding or discontinue rupatadine therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Drug Profile Summary
- Mechanism of Action: Selective peripheral H1 receptor antagonist and PAF antagonist.
- Side Effects: Common: Somnolence, headache, dizziness, dry mouth, fatigue. Serious: Hypersensitivity reactions, QT prolongation, torsades de pointes.
- Contraindications: Hypersensitivity, QT prolongation, cardiac arrhythmias, concomitant use of CYP3A4 inhibitors or other QT-prolonging drugs.
- Drug Interactions: CYP3A4 inhibitors, QT-prolonging drugs, CNS depressants, grapefruit juice.
- Pregnancy & Breastfeeding: Use with caution; preferably avoid during pregnancy. Caution advised during breastfeeding.
- Dosage: Adults: 10mg once daily. Children (2-11 years): 2.5mg (10-25kg) or 5mg (≥25 kg) once daily.
- Monitoring Parameters: Monitor for adverse reactions, especially cardiac effects (QT prolongation) and liver function.
Popular Combinations
No specific drug combinations are routinely recommended. Rupatadine is typically used as monotherapy for allergic rhinitis and urticaria.
Precautions
- General Precautions: Assess for hypersensitivity, renal/hepatic dysfunction, cardiac history, and concomitant medications.
- Pregnant Women: Avoid unless clearly necessary.
- Breastfeeding Mothers: Use with caution; consider discontinuing breastfeeding or the drug.
- Children & Elderly: Oral solution for children 2-11 years. Use with caution in the elderly due to increased sensitivity to side effects.
- Lifestyle Considerations: Alcohol may potentiate sedation. Driving or operating machinery should be avoided until individual response is assessed.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rupatadine?
A: Adults and adolescents (12 years and older): 10 mg once daily. Children (2-11 years): 2.5 mg (for 10 to <25 kg) or 5 mg (for ≥25 kg) once daily. Not recommended for children younger than 2 years.
Q2: What are the most common side effects of Rupatadine?
A: The most common side effects are somnolence, headache, dizziness, dry mouth, and fatigue.
Q3: Can Rupatadine be taken with food?
A: Yes, Rupatadine can be taken with or without food.
Q4: Is Rupatadine safe during pregnancy?
A: Limited data are available on Rupatadine use in pregnancy. It’s generally recommended to avoid its use during pregnancy unless the benefits clearly outweigh the risks. Consult with a physician for personalized advice.
Q5: Can Rupatadine be used in patients with liver or kidney problems?
A: Rupatadine is not recommended for patients with severe hepatic or renal impairment due to the lack of clinical data in these populations.
Q6: What should I do if I miss a dose of Rupatadine?
A: Take the missed dose as soon as you remember. If it’s almost time for your next dose, skip the missed dose and take your next dose at the regular time. Do not double the dose.
Q7: What are the serious side effects of Rupatadine?
A: Serious side effects are rare but can include allergic reactions (anaphylaxis, angioedema), QT prolongation, and a specific type of irregular heartbeat called torsades de pointes. Seek immediate medical attention if these occur.
Q8: Does Rupatadine interact with other medications?
A: Yes, Rupatadine can interact with certain medications, especially strong CYP3A4 inhibitors (like ketoconazole and erythromycin), and other QT-prolonging drugs. It is important to inform your doctor about all medications you are taking, including over-the-counter drugs and supplements.
Q9: Can I drink alcohol while taking Rupatadine?
A: Alcohol may enhance the sedative effects of Rupatadine. Concomitant use is not recommended.
Q10: Is Rupatadine safe for breastfeeding mothers?
A: Rupatadine is excreted in animal milk. It is unknown whether it is excreted in human milk. Caution should be exercised when prescribing to lactating women. Consider the benefits of breastfeeding for the child and the benefits of therapy for the woman when making decisions about whether to discontinue breastfeeding or discontinue/abstain from Rupatadine therapy. Consult with a physician for personalized advice.
