Bilanta M

Indications

Bilanta M is indicated for the Symptomatic treatment of allergic rhino-conjunctivitis (seasonal and perennial)

Adverse Effects

Bilastine Bilastine-related adverse events included an increase in somnolence (2/197, 1.0%), an elevation of aspartate aminotransferase levels (1/197, 0.5%), an increase in γ-glutamyltransferase levels (1/197, 0.5%), nocturia (1/197, 0.5%), headaches and asteatosis (7/197, 3.6% for both)

Drug Interactions

Interaction with ketoconazole or erythromycin: Concomitant intake of bilastine 20 mg o.d. and ketoconazole 400 mg o.d. or erythromycin 500 mg t.i.d. increased bilastine AUC 2-fold and Cmax 2-3 fold. These changes can be explained by interaction with intestinal efflux transporters, since bilastine is substrate for P-gp and not metabolised These changes do not appear to affect the safety profile of bilastine and ketoconazole or erythromycin, respectively. Other medicinal products that are substrates or inhibitors of P-gp, such as cyclosporine, may likewise have the potential to increase plasma concentrations of bilastine. Interaction with diltiazem: Concomitant intake of bilastine 20 mg o.d. and diltiazem 60 mg o.d. increased Cmax of bilastine by 50%. This effect can be explained by interaction with intestinal efflux transporters, and does not appear to affect the safety profile of bilastine. Interaction with alcohol: The psychomotor performance after concomitant intake of alcohol and 20 mg bilastine o.d. was similar to that observed after intake of alcohol and placebo. Interaction with lorazepam: Concomitant intake of bilastine 20 mg o.d. and lorazepam 3 mg o.d. for 8 days did not potentiate the depressant CNS effects of lorazepam

Mechanism of Action

Bilastine is a non-sedating, long-acting histamine antagonist with selective peripheral H1 receptor antagonist affinity and no affinity for muscarinic receptors. Bilastine inhibited histamine-induced wheal and flare skin reactions for 24 hours following single doses. Montelukast: Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLT1 receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or -adrenergic receptor). Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.

Pharmacokinetics

The half life of Bilastine in Bilanta M is 14.5 hours; half life of Montelukast in Bilanta M is 2.7-5.5 hours

Absorption, Distribution, Metabolism & Excretion

Montelukast Absorption Montelukast is rapidly absorbed following oral administration. For the 10 mg film-coated tablet, the mean peak plasma concentration (Cmax) is achieved 3 hours (Tmax) after administration in adults in the fasted state. The mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal. Distribution Montelukast is more than 99% bound to plasma proteins. Studies in rats with radiolabelled montelukast indicate minimal distribution across the blood-brain barrier. Biotransformation Montelukast is extensively metabolised. Cytochrome P450 2C8 is the major enzyme in the metabolism of montelukast. Additionally CYP 3A4 and 2C9 may have a minor contribution, although itraconazole, an inhibitor of CYP 3A4, was shown not to change pharmacokinetic variables of montelukast in healthy subjects that received 10 mg montelukast daily. Elimination The plasma clearance of montelukast averages 45 ml/min in healthy adults. Following an oral dose of radiolabelled montelukast, 86% of the radioactivity was recovered in 5-day faecal collections and <0.2% was recovered in urine. Bilastine Absorption Bilastine is rapidly absorbed after oral administration with a time to maximum plasma concentration of around 1.3 hours. No accumulation was observed. The mean value of bilastine oral bioavailability is 61%. Distribution At therapeutic doses bilastine is 84-90% bound to plasma proteins. Biotransformation Bilastine did not induce or inhibit activity of CYP450 isoenzymes in in vitro studies. Elimination Almost 95% of the administered dose is recovered in urine (28.3%) and faeces (66.5%) as unchanged bilastine, confirming that bilastine is not significantly metabolized in humans. The mean elimination half-life calculated in healthy volunteers was 14.5 h.

Drug Use in Pregnancy

Bilastine: Pregnancy: There are no or limited amount of data from the use of bilastine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity, parturition or postnatal development As a precautionary measure, it is preferable to avoid the use of Bilastine during pregnancy. Breast-feeding: The excretion of bilastine in milk has not been studied in humans. Available pharmacokinetic data in animals have shown excretion of bilastine in milk. A decision on whether to continue/discontinue breast-feeding or to discontinue/abstain from Ilaxten therapy must be made taking into account the benefit of breastfeeding for the child and the benefit of bilastine therapy for the mother. Fertility: There are no or limited amount of clinical data. A study in rats did not indicate any negative effect on fertility. Montelukast: Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Montelukast should be used during pregnancy only if clearly needed. Nursing Mothers Studies in rats have shown that montelukast is excreted in milk. It is not known if montelukast is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when montelukast is given to a nursing mother.

Drug Use in Renal Impairment

Bilastine: Renal impairment Studies conducted in adults in special risk groups (renally impaired patients) indicate that it is not necessary to adjust the dose of bilastine in adults Renal Impairement: In patients with moderate or severe renal impairment coadministration of bilastine with P-glycoprotein inhibitors, such as e.g, ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem, may increase plasmatic levels of bilastine and therefore increase the risk of adverse effects of bilastine. Therefore, coadministration of bilastine and P-glycoprotein inhibitors should be avoided in patients with moderate or severe renal impairment. Montelukast: Renal Impairement:No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency

Drug Use in Hepatic Impairment

Bilastine: There is no clinical experience in adult patients with hepatic impairment. However, since bilastine is not metabolized and is eliminated as unchanged in urine and faeces, hepatic impairment is not expected to increase systemic exposure above the safety margin in adult patients. Therefore, no dosage adjustment is required in adult patients with hepatic impairment Montelukast: No dosage adjustment is recommended in patients with renal insufficiency

Drug Use in Pediatric Population

Bilastine: Paediatric population Efficacy and safety of bilastine in children under 2 years of age have not been established and there is little clinical experience in children aged 2 to 5 years, therefore bilastine should not be used in these age groups. Children 6 to 11 years of age with a body weight of at least 20 kg Bilastine 10 mg orodispersible tablets and bilastine 2.5 mg/mL oral solution are appropriate for administration to this population. The safety and efficacy of bilastine in renally and hepatically impaired children have not been established. Montelukast: Pediatric Use Safety and efficacy of montelukast have been established in adequate and well-controlled studies in pediatric patients with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults

Drug Use in Geriatric Population

Bilastine: Elderly No dosage adjustments are required in elderly patients Montelukast: No dosage adjustment in the elderly is required.