Bilastine / Rupatadine

Pharmacokinetics

High Resolution Pharmacokinetics

Indicators and dose

Clinical Indications and Off-Label Uses

• Allergic Rhinitis (Seasonal and Perennial): Symptomatic treatment of allergic rhinoconjunctivitis in adults and pediatric patients (bilastine approved in syrup from 6 years of age; rupatadine from 2 years of age).
• Chronic Spontaneous Urticaria (CSU): Relief of skin itching and reduction of the appearance of hives (hives) on the skin.
• Non-Allergic Rhinitis with Eosinophilia (NARES) (off-label): Symptomatic control of mucosal inflammation and refractory nasal pruritus.

Dosage and Clinical Adjustment

Bilastine:

• Adults and Adolescents (>12 years): 20 mg orally once a day, taken on an empty stomach.
• Children (6 to 11 years with a minimum weight of 20 kg): 10 mg orally once a day (orodispersible tablet formulation or oral solution).

Rupatadine:

• Adults and Adolescents (>12 years): 10 mg orally once a day, with or without food.
• Children (2 to 11 years):
  • Weight 25 kg: 5 mg (5 mL oral solution) once a day.
  • Weight from 10 kg to 24 kg: 2.5 mg (2.5 mL oral solution) once a day.

Adjustment in Renal or Liver Failure:

• Bilastine: No adjustment is required in renal or hepatic failure (it is eliminated unchanged).
• Rupatadine: Its use is not recommended in patients with moderate to severe renal or hepatic impairment due to the lack of clinical safety data and the high hepatic clearance of its metabolites.

Security

Absolute and Relative Contraindications

Absolute Contraindications

• Known hypersensitivity to the active ingredient or to the components of the oral formulation.
• Moderate to severe renal impairment concomitant with the use of strong P-gp inhibitors (such as erythromycin or ketoconazole) in the case of bilastine (risk of cumulative toxicity).

Relative Contraindications

• Concomitant use of rupatadine with strong cytochrome CYP3A4 inhibitors (erythromycin, voriconazole, ritonavir) or with grapefruit juice (multiplies systemic levels of rupatadine).
• Elderly patients with known congenital prolongation of the cardiac QT interval.

Adverse Effects (ADR) and Specific Toxicity

• Frequent (1%-10%): Mild drowsiness (incidence less than 1.5% for bilastine at standard doses, somewhat higher in rupatadine), headache, dizziness, temporary fatigue, dry mouth.
• Uncommon (0.1%-1%): Increased appetite (with possible transient weight gain, more reported with rupatadine), mild prolongation of the QT interval on the electrocardiogram (no clinical repercussion at recommended doses).
• Rare (<0.1%): Transient elevation of transaminases of hepatic origin or pancreatic amylase, dyspnea.

Critical Diet Alert: Bilastine and Food Intake

Intestinal absorption of bilastine is drastically reduced in the presence of food or fruit juices (especially grapefruit, apple or orange juice). This is due to direct interference with the sodium-dependent organic anion transporter (OATP1A2) at the enterocytic level:

Concomitant intake of grapefruit juice Inhibition of OATP1A2 Decrease in the bioavailability of Bilastine by 30-50%

The patient should be unequivocally instructed to take bilastine strictly 1 hour before or 2 hours after any intake of food or fruit juices to ensure its therapeutic efficacy.

Drug Interactions of Clinical Relevance

• Ketoconazole, Erythromycin or Clarithromycin: Increase the area under the curve (AUC) of bilastine and rupatadine by inhibiting P-gp (bilastine) and CYP3A4 (rupatadine).
• Alcohol or central nervous system depressants: Although they do not markedly enhance drowsiness compared to first-generation antihistamines (such as hydroxyzine), caution is advised in patients who require driving heavy machinery or motor vehicles.

Safety in Pregnancy and Breastfeeding

• Pregnancy: Not recommended. There are no clinical studies available in pregnant women. It is preferred to avoid its prescription, opting for antihistamines with a greater retrospective safety profile (such as cetirizine or loratadine).
• Breastfeeding: Not recommended. It is unknown if they are excreted in breast milk; Its use must be evaluated under the benefit-risk ratio.