Nixar® [Bilastine]

Pharmacological properties

bilastine is a long-acting antihistamine, does not cause a sedative effect, selectively binds to peripheral h1 receptors and does not bind to m-cholinergic receptors.

After a single application, bilastine within 24 hours inhibits the development of skin reactions caused by histamine, with blisters and erythema.

In clinical trials in which patients with allergic rhinoconjunctivitis (seasonal and year-round) participated, the use of bilastine at a dose of 20 mg 1 time per day for 14–28 days noted relief of symptoms of the disease, such as sneezing, nasal discharge, itching in the nose, nasal congestion, itchy eyes, lacrimation and redness of the eyes. The therapeutic effect of bilastine was maintained for 24 hours.

In the course of clinical studies in which patients with chronic idiopathic urticaria participated, the use of bilastine at a dose of 20 mg once a day for 28 days showed a decrease in the severity of itching and a decrease in the number and size of blisters; in addition, patients felt less discomfort caused by urticaria. Patients showed improved sleep and well-being.

Neither a clinically significant prolongation of the Q – T interval on the ECG, nor other disorders of the cardiovascular system were observed during clinical trials of bilastine.

Pharmacokinetics Suction. After oral administration, bilastine is rapidly absorbed, and its C_max in blood plasma is achieved 1.3 hours after administration. No accumulation of the drug in the body The average bioavailability when administered orally is 61%.

Distribution. According to in vitro and in vivo studies, bilastine is a substrate of P-glycoprotein and the OATP carrier protein. Bilastine is obviously not a substrate for the BCRP transporter or the OST, OAT1 and OAT3 transporter. In vitro studies do not suggest that in the systemic circulation, bilastine inhibits the activity of carrier proteins such as P-gp, MRP2, BCRP, BSEP, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2 and NTCP, since the ability to inhibit P-gp, OATP2B1 and OCT1 is negligible and is characterized by an IC50 value of ≥300 μm, which significantly exceeds the calculated value of C_max in blood plasma in case of its clinical use. Thus, such interactions are not clinically significant. However, similar studies indicate that bilastin inhibition of carrier proteins located in the intestinal mucosa (e.g. P-gp) cannot be ruled out. After application in therapeutic doses, bilastine binds to plasma proteins by 84–90%.

Biotransformation. In in vitro studies, bilastine did not show the ability to induce or inhibit the activity of cytochrome P450 isoenzymes.

According to a study conducted with the participation of volunteers, after a single application ¹⁴C-bilastine at a dose of 20 mg almost 95% of the administered dose appeared in urine and feces (28.3 and 66.5%, respectively) as unchanged bilastine, from which it can be concluded that bilastine is slightly metabolized in the human body. Average T_½ bilastine in healthy volunteers is 14.5 hours.

Linearity. In the dose range from 5 to 220 mg, the pharmacokinetic parameters of bilastine change in direct proportion to the dose; however, they differ slightly among different healthy volunteers.

Indications

Symptomatic treatment for allergic rhinoconjunctivitis (seasonal and year-round) and urticaria.

Application

Adults and children (from the age of 12 years). the recommended dose is 20 mg (1 tablet) once a day to alleviate the symptoms of allergic rhinoconjunctivitis (seasonal and year-round) and urticaria.

The tablet should be taken orally 1 hour before or 2 hours after a meal or fruit juice.

Elderly patients.Elderly patients do not need dose adjustment. The experience of using the drug in patients over the age of 65 is limited.

Impaired renal function. Patients with impaired renal function do not require dose adjustment.

Impaired liver function. There is no experience with the clinical use of the drug in patients with impaired liver function. Since bilastine is not metabolized and excreted mainly by the kidneys, impaired liver function should not lead to an increase in its systemic effect to a dangerous level. Therefore, patients with impaired liver function dose adjustment is not required.

Duration of treatment. In patients with allergic rhinitis, the drug should be used only during contact with allergens. For people with seasonal allergic rhinitis, treatment can be discontinued after symptoms have been relieved and resumed after they return. For patients with perennial allergic rhinitis, the drug can be used continuously during the period of contact with allergens. In patients with urticaria, the duration of therapy depends on the nature and duration of the symptoms, as well as on their dynamics.

Contraindications

Hypersensitivity to the active substance (bilastine) or to any of the excipients.

Side effects

In clinical trials in patients with allergic rhinoconjunctivitis or chronic idiopathic urticaria, side effects with bilastine at a dose of 20 mg occurred at about the same frequency as with placebo (12.7 and 12.8%). the results of the studies indicate that when using bilastine at a dose of 20 mg, adverse reactions such as headache, drowsiness, dizziness and fatigue were most often noted. at approximately the same frequency, these adverse events were detected in patients taking placebo.

The following are adverse reactions whose association with bilastine is recognized, or at least possible, and which were noted in the clinical development program in more than 0.1% of patients receiving bilastine at a dose of 20 mg.

By frequency, side effects are divided into the following categories: very often (≥1 / 10); often (≥1 / 100 and 1/10); sometimes (≥1 / 1000 and 1/100); rarely (≥1 / 10,000 and 1/1000); very rarely (1/10 000), unknown (the available data do not allow an estimate).

Infections and parasitic diseases: sometimes - herpes of the oral cavity.

Violation of nutrition and metabolism: sometimes - increased appetite.

From the psyche: sometimes - anxiety, insomnia.

From the side of the organ of hearing and balance: sometimes - tinnitus, dizziness.

On the part of the cardiovascular system: sometimes - blockade of the right leg of the bundle of His, sinus arrhythmia, lengthening of the Q – T interval on the ECG, other disturbances on the ECG.

From the nervous system: often - drowsiness, headache; sometimes dizziness.

From the respiratory system: sometimes - shortness of breath, discomfort in the nose, dry nose.

From the digestive system: sometimes - pain in the upper abdomen, abdominal pain, nausea, discomfort in the abdomen, diarrhea, dry mouth, dyspepsia, gastritis.

From the skin and subcutaneous adipose tissue: sometimes - itching.

General and local disorders: sometimes - fatigue, thirst, aggravation of existing diseases, fever, asthenia.

Additional research methods: increased activity of gamma-glutamyltranspeptidase, AlAT, AsAT, increased levels of creatinine in the blood, increased levels of TG in the blood, increased body weight.

special instructions

In patients with moderate or severe impaired renal function, the use of bilastine simultaneously with p-glycoprotein inhibitors (ketoconazole, erythromycin, cyclosporin, ritonavir, diltiazem, etc.) can lead to an increase in the concentration of bilastine in blood plasma and, therefore, to an increased risk of side effects .therefore, patients with moderate or severe impaired renal function, bilastin should not be used concurrently with p-glycoprotein inhibitors.

Use during pregnancy and lactation. Fertility. Clinical data are limited. Animal studies have not revealed a negative effect of the drug on fertility.

Pregnancy. There are no data on the use of bilastine in pregnant women.

In animal studies, no adverse effects of the drug (direct or indirect) on reproductive function, childbirth or postnatal development were noted. In view of safety, Nixar should not be used during pregnancy.

Lactation. Data on whether bilastine passes into breast milk of women is not available. The excretion of bilastine with milk in animals was not studied. The decision on the extension or termination of breastfeeding, as well as on the continuation or termination of therapy with the drug Nixar should be made taking into account the benefits of breastfeeding for the child, on the one hand, and the need for bilastine therapy for the mother, on the other.

Children. The safety and effectiveness of bilastine for children under 12 years of age have not been confirmed.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. According to a study of the effect of bilastine on the ability to drive vehicles, the use of bilastine in a dose of 20 mg does not affect the ability to drive vehicles. However, patients should be informed that in some cases, the drug can cause drowsiness and, thus, affect the ability to drive vehicles and work with mechanisms.

Interactions

Interaction with food. food reduces by 30% the bioavailability of oral bilastine.

Interaction with grapefruit juice. In the case of using bilastine at a dose of 20 mg simultaneously with grapefruit juice, the bioavailability of bilastine was reduced by 30%. A similar effect can be observed in the case of the use of other fruit juices. The degree of decrease in bioavailability may vary depending on the producer of juice and fruit from which it is derived. This interaction is due to the ability of fruit components to suppress the activity of the protein - the carrier of organic anions OATP1A2, for which bilastine is a substrate. Drugs that are substrates or inhibitors of OATP1A2 (e.g. ritonavir or rifampicin) can also reduce the concentration of bilastine in blood plasma.

Interaction with ketoconazole or erythromycin. In the case of taking bilastine simultaneously with ketoconazole or erythromycin AUC, bilastine increased by 2 times, and C_max - 2-3 times. Similar effects can be explained by the interaction at the level of carrier proteins responsible for the elimination of drugs from intestinal cells, since bilastine is a substrate of P-glycoprotein and is not metabolized. The safety profile of bilastine, on the one hand, and ketoconazole or erythromycin, on the other, these effects are probably not affected. Other drugs that are substrates or inhibitors of P-glycoprotein (for example, cyclosporine) can increase the concentration of bilastine in blood plasma.

Interaction with diltiazem. In the case of taking bilastine at a dose of 20 mg simultaneously with diltiazem at a dose of 60 mg C_max bilastine increased by 50%. A similar effect can be explained by the interaction at the level of carrier proteins, responsible for the removal of drugs from intestinal cells; This effect probably does not affect the bilastine safety profile.

Interaction with ethyl alcohol. After the simultaneous intake of alcohol and bilastine at a dose of 20 mg, the psychomotor functions were at the same level as after the simultaneous intake of alcohol and placebo.Bilastine does not affect psychomotor function when taken with ethyl alcohol.

Interaction with lorazepam. In the case of the use of bilastine at a dose of 20 mg simultaneously with lorazepam at a dose of 3 mg for 8 days, the inhibitory effect of lorazepam on the central nervous system was not detected.

Overdose

Data regarding acute overdose were obtained only during clinical trials. with the use of bilastine in doses exceeding therapeutic by 10–11 times, side effects in healthy volunteers occurred 2 times more often than with placebo. side effects that were noted more often included dizziness, headache, and nausea. no serious adverse reactions and a significant increase in the duration of the q – tc interval were noted. in a cross-sectional study measuring q – t / q – tc intervals, in which the effect of repeated use of bilastine on ventricular repolarization was studied, no statistically significant lengthening of the q – tc interval was revealed.

Treatment. In case of an overdose, symptomatic and supportive therapy is recommended. The specific antidote for bilastine is unknown.

Storage conditions

It does not require special storage conditions.