Mizolastine

Approved Indications:

• Seasonal Allergic Rhinitis (Hay Fever):
  Indicated for the relief of nasal and ocular symptoms such as sneezing, rhinorrhea, nasal congestion, and itching caused by pollen or other airborne allergens.
• Perennial Allergic Rhinitis:
  Used for managing year-round allergic symptoms due to allergens like dust mites, animal dander, and mold.
• Chronic Idiopathic Urticaria (CIU):
  Effective for treating chronic hives, providing relief from wheals and itching in adults and adolescents.

Clinically Accepted Off-Label Uses:

• Allergic Conjunctivitis (associated with allergic rhinitis):
  Occasionally used to alleviate eye symptoms as part of systemic antihistamine therapy.
• Atopic Dermatitis (as adjunctive therapy):
  Used off-label to relieve pruritus in allergic skin conditions when combined with topical treatments.

Adults and Adolescents (≥12 years):

• Dose: 10 mg orally once daily
• Route: Oral, with or without food
• Frequency: Once every 24 hours
• Duration: As long as symptomatic relief is needed or as directed by a physician

Pediatric Use (<12 years):

• Not recommended due to insufficient safety and efficacy data.

Elderly Patients (≥65 years):

• No specific dosage adjustment required, but caution is advised due to potential age-related decline in renal or hepatic function.

Renal Impairment:

• Mild to Moderate Impairment: Use with caution; monitor for accumulation.
• Severe Impairment (Creatinine clearance <30 mL/min): Use is contraindicated due to risk of drug accumulation.

Hepatic Impairment:

• Use with caution. Since the drug undergoes hepatic metabolism, exposure may be increased.

Administration Instructions:

• Tablets should be swallowed whole with water.
• Do not chew or crush the tablets.
• Best taken at the same time each day to maintain consistent plasma levels.
• Avoid co-administration with grapefruit juice or QT-prolonging medications.

Mizolastine is a selective, second-generation H1-receptor antagonist. It blocks the action of histamine by competitively binding to peripheral H1 receptors, thereby preventing histamine-induced allergic symptoms such as sneezing, itching, and vasodilation. It does not significantly cross the blood-brain barrier, which minimizes central nervous system effects like sedation. Additionally, it stabilizes vascular permeability, reducing inflammation and swelling in allergic conditions.

• Absorption: Rapidly absorbed after oral administration with peak plasma levels occurring within 1 to 2 hours.
• Bioavailability: Approximately 65%
• Distribution: Highly protein-bound (~98%)
• Metabolism: Extensively metabolized in the liver, mainly via the CYP3A4 enzyme system.
• Metabolites: Inactive metabolites
• Elimination: Excreted primarily via urine and to a lesser extent in feces
• Half-life: Approximately 13 to 15 hours
• Onset of Action: Within 1 hour after dosing

• Pregnancy:
  Mizolastine has not been assigned a formal FDA pregnancy category. Use is not recommended during pregnancy unless clearly needed. Animal studies have not demonstrated teratogenic effects, but human data are limited.
• Lactation:
  The drug is excreted in breast milk. Due to the potential for adverse effects in nursing infants, breastfeeding is not recommended during treatment.
• Caution:
  Use only if the potential benefit justifies the potential risk to the fetus or infant.

• Primary Class: Second-Generation Antihistamine
• Subclass: Selective Peripheral H1-Receptor Antagonist (Non-sedating)

• Hypersensitivity to Mizolastine or any of its components
• Known QT interval prolongation or history of torsades de pointes
• Severe renal impairment (Creatinine clearance <30 mL/min)
• Severe hepatic impairment
• Concurrent use with QT-prolonging agents (e.g., erythromycin, ketoconazole, certain antipsychotics)

• Cardiac Risk:
  Mizolastine may prolong the QT interval and increase the risk of arrhythmias. Caution is advised in patients with existing heart disease, electrolyte imbalance, or those taking other QT-prolonging drugs.
• Renal and Hepatic Impairment:
  Use cautiously in patients with renal or hepatic dysfunction. Dose adjustments may be necessary.
• CNS Effects:
  Although generally non-sedating, occasional drowsiness or dizziness may occur.
• Avoid Alcohol:
  Concomitant alcohol use may potentiate CNS effects.
• Monitoring:
  Consider ECG monitoring in high-risk individuals or if co-administered with other interacting drugs.

Common Side Effects:

• Central Nervous System: Headache, dizziness, mild somnolence
• Gastrointestinal: Nausea, dry mouth, abdominal pain
• General: Fatigue, weakness

Uncommon/Rare Side Effects:

• Cardiac: QT prolongation, palpitations, tachycardia
• Hepatic: Elevated liver enzymes
• Dermatological: Rash, pruritus

Serious Adverse Effects:

• Anaphylaxis (rare)
• Torsades de pointes or other ventricular arrhythmias in predisposed individuals

Timing:

• Most side effects occur within the first few days of treatment and are typically mild and self-limiting.

Major Drug Interactions:

• QT-Prolonging Drugs: Co-administration with macrolide antibiotics (e.g., erythromycin), antifungals (e.g., ketoconazole), and certain antipsychotics may increase the risk of torsades de pointes.
• CYP3A4 Inhibitors: May increase plasma levels of Mizolastine and enhance toxicity. Examples include ritonavir, verapamil, and itraconazole.
• Alcohol: May increase the risk of sedation or dizziness, even though Mizolastine is generally non-sedating.
• Antacids: May impair absorption; administer with a time gap of at least 2 hours.

Enzyme Involvement:

• Mizolastine is a CYP3A4 substrate; avoid concurrent use with strong inhibitors or inducers of this enzyme.

• Safety Monitoring:
  EMA and other regulatory bodies continue to advise against use in patients at risk of cardiac arrhythmia due to QT prolongation.
• Clinical Guidelines:
  No recent changes in dosage or approved indications. Safety warnings have been reiterated regarding cardiac risk and hepatic impairment.
• Formulary Notes:
  Some countries restrict availability due to potential cardiac effects; clinicians should evaluate risk-benefit before prescribing.

• Temperature: Store at or below 30°C
• Humidity: Protect from moisture; store in a dry environment
• Light: Keep in the original container to protect from light exposure
• Handling Instructions:
• Do not use beyond the expiration date
• Do not crush or split tablets
• Keep out of reach of children
• No refrigeration required