Usage
Azelastine + Fluticasone Propionate is prescribed for the relief of symptoms of moderate to severe seasonal and perennial allergic rhinitis (hay fever and other nasal allergies) when treatment with either an intranasal antihistamine or corticosteroid alone is insufficient. It’s also indicated for related eye symptoms (rhinoconjunctivitis) in certain cases.
Pharmacological Classification:
This drug is a combination product containing:
- Azelastine: H1-receptor antagonist (antihistamine).
- Fluticasone Propionate: Corticosteroid (intranasal glucocorticoid).
Mechanism of Action:
Azelastine competes with histamine for H1-receptor sites, reducing the allergic response. Fluticasone propionate exerts anti-inflammatory activity, suppressing the release of inflammatory mediators, and reducing nasal edema and mucus secretion.
Alternate Names
Azelastine hydrochloride + Fluticasone propionate.
Brand Names: Dymista®, APO-Azelastine/Fluticasone, MYLAN-Azelastine/Fluticasone.
How It Works
Pharmacodynamics:
Azelastine inhibits histamine release from mast cells, reducing symptoms like sneezing, rhinorrhea, nasal itching, and congestion. Fluticasone propionate reduces inflammation in the nasal passages, further alleviating congestion and other symptoms.
Pharmacokinetics:
- Absorption: Both drugs are absorbed systemically following intranasal administration, but the extent is limited.
- Metabolism: Fluticasone propionate is extensively metabolized in the liver, primarily by CYP3A4 enzymes. Azelastine metabolism is less well-characterized.
- Elimination: Fluticasone propionate is mainly excreted in feces, with a minor portion in urine. Azelastine’s elimination pathways are not fully elucidated, but likely involve both renal and hepatic routes.
Mode of Action:
Azelastine acts as a competitive antagonist at the H1 receptor, preventing histamine from binding and triggering the allergic cascade. Fluticasone propionate binds to glucocorticoid receptors in the nasal mucosa, modulating gene expression and reducing the production of inflammatory mediators.
Receptor binding, enzyme inhibition, or neurotransmitter modulation:
- Azelastine: H1 receptor antagonist.
- Fluticasone propionate: Glucocorticoid receptor agonist.
Elimination pathways:
- Azelastine: Renal and hepatic.
- Fluticasone propionate: Primarily hepatic metabolism (CYP3A4) with fecal excretion.
Dosage
Standard Dosage
Adults:
One spray in each nostril twice daily (morning and evening).
Children:
- 6 years and older: One spray in each nostril twice daily.
- Younger than 6 years: Not recommended, as safety and efficacy haven’t been established.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required. However, start with the lowest effective dose and monitor for adverse effects.
- Patients with Renal Impairment: No specific dosage adjustment recommendations are available. Exercise caution.
- Patients with Hepatic Dysfunction: In mild to moderate hepatic impairment, no dosage adjustment is usually needed. Use cautiously in severe hepatic impairment, as systemic exposure may be increased. Close monitoring is advised.
- Patients with Comorbid Conditions: Consider individual patient factors and comorbid conditions that might affect drug response.
Clinical Use Cases
Azelastine + Fluticasone is typically used for outpatient management of allergic rhinitis and not indicated for the listed clinical scenarios (intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations). Other formulations or routes of administration of corticosteroids may be more appropriate for these scenarios.
Dosage Adjustments
Adjust dosages based on individual patient response, tolerability, and underlying medical conditions. Consider drug interactions and potential systemic effects, especially with long-term or high-dose use.
Side Effects
Common Side Effects:
Epistaxis (nosebleeds), headache, dysgeusia (altered taste), unpleasant smell, nasal dryness/irritation, somnolence (drowsiness), fatigue.
Rare but Serious Side Effects
Hypersensitivity reactions (including anaphylaxis, angioedema, bronchospasm), glaucoma, increased intraocular pressure, cataract, blurred vision, nasal septal perforation, nasal ulcers, adrenal suppression, growth retardation in children.
Long-Term Effects
Nasal septal perforation, cataracts, glaucoma, adrenal suppression, growth retardation (in children), reduced bone density (osteoporosis - rare).
Adverse Drug Reactions (ADR)
Anaphylaxis, angioedema, severe bronchospasm, adrenal crisis.
Contraindications
Hypersensitivity to azelastine, fluticasone propionate, or any of the drug’s components. Untreated fungal, bacterial, or tuberculous infections of the respiratory tract.
Drug Interactions
- Ritonavir and other potent CYP3A4 inhibitors: Coadministration is not recommended, as they can significantly increase fluticasone propionate plasma concentrations, leading to systemic corticosteroid effects (e.g., Cushing’s syndrome, adrenal suppression). Use caution with other potent CYP3A4 inhibitors like ketoconazole.
- Alcohol and CNS depressants: Concurrent use may increase drowsiness and impair CNS performance.
- Other medications: Consult drug interaction resources for potential interactions with other medications.
Pregnancy and Breastfeeding
Pregnancy: Use only if the potential benefit outweighs the potential risk to the fetus. There are limited human data, but animal studies have shown some adverse effects at high doses.
Breastfeeding: It’s unknown whether the drug is excreted in breast milk. Exercise caution and consider the potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Azelastine: H1 receptor antagonist; Fluticasone propionate: Glucocorticoid receptor agonist.
- Side Effects: Epistaxis, headache, dysgeusia, nasal irritation, somnolence. Serious side effects: Hypersensitivity reactions, glaucoma, adrenal suppression.
- Contraindications: Hypersensitivity, untreated respiratory tract infections.
- Drug Interactions: Ritonavir, potent CYP3A4 inhibitors, alcohol, CNS depressants.
- Pregnancy & Breastfeeding: Use cautiously. Potential risk to the fetus/infant.
- Dosage: Adults and children ≥6 years: One spray per nostril twice daily.
- Monitoring Parameters: Nasal examination (long-term use), eye examination (patients with eye disorders), growth in children (long-term use).
Popular Combinations
Azelastine + Fluticasone is itself a combination product. Additional combinations are generally not recommended unless specifically indicated and under careful medical supervision.
Precautions
- General Precautions: Assess for hypersensitivity, pre-existing infections, nasal conditions, and ocular conditions.
- Pregnant Women: Assess benefit versus risk.
- Breastfeeding Mothers: Monitor infant for adverse effects.
- Children & Elderly: Use with caution in elderly patients, not recommended in children <6 years.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution regarding driving or operating machinery due to potential somnolence.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Azelastine + Fluticasone Propionate?
A: One spray in each nostril twice daily for adults and children 6 years and older.
Q2: Can this medicine be used in children under 6 years of age?
A: No, it is not recommended for use in children under 6, as safety and efficacy have not been established in this age group.
Q3: What are the most common side effects?
A: Epistaxis, headache, altered taste, and nasal irritation.
Q4: Are there any serious side effects I should be aware of?
A: Yes, although rare, serious side effects like glaucoma, cataracts, nasal septal perforation, adrenal suppression, and hypersensitivity reactions can occur.
Q5: Can I use this medicine if I am pregnant or breastfeeding?
A: Consult your doctor. It should be used during pregnancy or breastfeeding only if the potential benefit outweighs the potential risk to the fetus or infant.
Q6: What should I do if I experience nosebleeds while using this medication?
A: Consult your doctor. While mild and infrequent nosebleeds are common, persistent or severe bleeding warrants medical attention.
Q7: Can I drink alcohol while taking this medication?
A: It’s best to avoid alcohol as it can increase drowsiness and impair your central nervous system function.
Q8: Are there any drug interactions I should be aware of?
A: Yes, avoid using this medication with ritonavir and other potent CYP3A4 inhibitors. Use caution with other medications that cause drowsiness. Inform your doctor about all medications you are taking.
Q9: Can this medicine be used long-term?
A: Yes, it can be used long-term, but regular monitoring for potential side effects, especially nasal and ocular changes, is necessary.
Q10: What should I do if my symptoms do not improve after using this medication?
A: Consult your physician. They may suggest adjusting the dosage, switching to a different medication, or exploring other treatment options.
