Zodak Express allergy remedy tablets No. 28
A country
Czech Republic
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Active substance
Levocetirizine
Compound
Active substance: levocetirizine hydrochloride 5.00 mg.
pharmachologic effect
Pharm acodynamics. Levocetirizine, the (R)-enantiomer of cetirizine, is an inhibitor of peripheral H1 histamine receptors, the affinity of which is 2 times higher than that of cetirizine. After a single dose of levocetirizine, binding of H1-histamine receptors was observed by 90% after 4 hours and by 57% after 24 hours. It has an effect on the histamine-dependent stage of allergic reactions; reduces the migration of eosinophils, reduces vascular permeability, limits the release of inflammatory mediators. Prevents the development and facilitates the course of allergic reactions, has an antiexudative and antipruritic effect; has virtually no anticholinergic and antiserotonin effects. In therapeutic doses it has virtually no sedative effect. Action begins 12 minutes after a single dose in 50% of patients, 1 hour in 95% of patients, and continues for 24 hours. Does not affect the QT interval on the ECG. Pharmacokinetics: Pharmacokinetics are linear, independent of dose and time, and vary slightly among individuals. Absorption: After oral administration, absorption of levocetirizine occurs quickly and in large quantities. The maximum plasma concentration is reached 0.9 hours after taking the drug. Equilibrium concentration is established after 2 days. The maximum plasma concentration after a single dose of 5 mg of levocetirizine is 270 ng/ml, and after a repeated dose of 5 mg - 308 ng/ml. The degree of absorption depends on the dose and is not affected by food intake, but when eating food, the maximum concentration decreases and its achievement slows down. Distribution: Levocetirizine is 90% bound to plasma proteins. The volume of distribution is 0.4 l/kg. There are no data on the distribution of levocetirizine in tissues and its penetration through the blood-brain barrier in humans; Levocetirizine passes into breast milk. Metabolism: In humans, less than 14% of the dose of levocetirizine is metabolized, since the expected differences in the pharmacokinetic profile of levocetirizine due to genetic polymorphism or concomitant use of enzyme inhibitors are insignificant . Metabolic transformations consist of oxidation of the aromatic ring, N- and O-dealkylation and conjugation with taurine. The dealkylation process is mainly carried out by the CYP3A4 isoenzyme, while the oxidation of the aromatic ring occurs through many and/or unidentified CYP isoforms. Levocetirizine, when taken orally at a dose of 5 mg and/or when maximum plasma concentrations are exceeded, does not affect the activity of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, 3A4. Due to limited metabolism and the absence of metabolic inhibitory activity, the interaction of levocetirizine at the level of metabolism with other substances is unlikely. Elimination. The half-life in adults is 7.9 ± 1.9 hours. The average observed total clearance is 0.63 ml/min/kg. Levocetirizine is predominantly excreted in the urine, on average, about 85.4% of the dose taken by glomerular filtration and active tubular secretion. Excretion through the intestines (with feces) is only 12.9% of the dose taken. Patients with renal failure. The total clearance of levocetirizine depends on the creatinine clearance (CC). Therefore, patients with moderate and severe renal failure are recommended to increase the intervals between doses of the drug in accordance with the QC. In patients with anuria and end-stage renal disease, the total clearance of levocetirizine is reduced by approximately 80% compared to healthy individuals. The amount of levocetirizine excreted during a standard 4-hour hemodialysis procedure is less than 10%.
Indications for use
Treatment of symptoms of year-round (persistent) and seasonal (intermittent) allergic rhinitis and allergic conjunctivitis, such as itching, sneezing, nasal congestion, rhinorrhea. lacrimation, conjunctival hyperemia. Hay fever (hay fever). Urticaria, including chronic idiopathic urticaria. Quincke's edema (as an auxiliary therapy). Other allergic dermatoses, accompanied by itching and rashes.
Mode of application
The tablet should be taken orally, without chewing and with liquid, regardless of meals. It is recommended to take the daily dose in one dose. Adults, teenagers and children over 6 years old. The recommended daily dose is 5 mg (1 tablet). Elderly patients. In elderly patients with moderate and severe renal failure, dose adjustment is recommended. Patients with impaired renal function. The interval between doses of the drug is determined individually taking into account renal function. In children with impaired function kidney dose is adjusted individually taking into account creatinine clearance and body weight. There are no separate data on use in children with impaired renal function. Patients with impaired liver function. In case of isolated impaired liver function, no dose adjustment is required. In patients with hepatic-renal insufficiency, dose adjustment is recommended. Duration of treatment. Treatment of allergic rhinitis is carried out in accordance with the course of the disease; The drug can be stopped when symptoms disappear and resumed if symptoms recur. In the case of chronic allergic rhinitis, long-term treatment may be prescribed during the period of exposure to allergens. Currently, clinical experience with the use of levocetirizine in the form of 5 mg film-coated tablets is limited to 6 months.
Interaction
There have been no drug interaction studies with levocetirizine, including studies with inducers of the CYP3A4 isoenzyme. The extent of absorption of levocetirizine was not reduced by food, although the rate of absorption was reduced. In sensitive patients, concomitant use of levocetirizine and alcohol or other substances that have a depressant effect on the central nervous system (CNS) ), may enhance the effect on the central nervous system.
Side effect
Immune system disorders. Very rare: hypersensitivity reactions, including anaphylactic reactions. Nervous system disorders. Often: headache; uncommon: drowsiness; very rare: aggression, agitation, hallucinations, depression, convulsions. Visual disorders. Very rare: visual disturbances. Cardiac disorders. Very rare: palpitations, tachycardia. Disorders of the respiratory system, chest and mediastinal organs. Very rare: shortness of breath. Gastrointestinal disorders. Often: dryness of the oral mucosa; uncommon: abdominal pain; very rare: nausea, diarrhea. Liver and biliary tract disorders. Very rare: hepatitis. Skin and subcutaneous tissue disorders. Very rare: angioedema, itching, rash, including drug rash, urticaria. Musculoskeletal disorders and connective tissue. Very rare: myalgia. General disorders. Often: fatigue; uncommon: asthenia. Violations of laboratory and instrumental data. Very rare: abnormal liver function tests, weight gain.
Contraindications
Hypersensitivity to levocetirizine and other piperazine derivatives or to any of the auxiliary components of the drug. Terminal renal failure with CC less than 10 ml/min. Pregnancy. Children under 6 years of age (for this dosage form). Congenital galactose intolerance, lactase deficiency or glucose malabsorption - galactose (due to the lactose content in the preparation).
Overdose
Symptoms: Symptoms of overdose may include drowsiness in adults and agitation and restlessness alternating with drowsiness in children. Treatment: There are no specific antidotes for levocetirizine. In case of overdose, symptomatic or supportive treatment is recommended. If little time has passed after taking the drug, gastric lavage should be performed. Levocetirizine is practically not excreted during hemodialysis.
special instructions
With caution. Caution must be exercised when taken simultaneously with alcohol. Chronic renal failure with CC more than 10 ml/min, but less than 50 ml/min (dosage adjustment required). Older age (possible decrease in glomerular filtration). Use during pregnancy and during pregnancy period of breastfeeding. The use of the drug during pregnancy is contraindicated. Levocetirizine is excreted in breast milk, therefore, if it is necessary to use the drug during lactation, it is recommended to stop breastfeeding. During treatment with the drug, it is not recommended to take ethanol. Impact on the ability to drive vehicles or engage in other potentially hazardous activities Levocetirizine, when taken in recommended doses, does not have a negative effect on attention and speed of psychomotor reactions and the ability to drive vehicles. However, during the period of taking the drug, it is advisable to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Pharmacodynamics
Levocetirizine - the active ingredient of the drug Allerway Express - (R)-enantiomer of cetirizine, a powerful and selective histamine antagonist that blocks H1 histamine receptors.
Levocetirizine has an effect on the histamine-dependent stage of allergic reactions, and also reduces the migration of eosinophils, reduces vascular permeability, and limits the release of inflammatory mediators.
Levocetirizine prevents the development and facilitates the course of allergic reactions, has antiexudative and antipruritic effects, and has virtually no anticholinergic and antiserotonin effects. In therapeutic doses it does not have a sedative effect.
With a single dose of levocetirizine, receptor binding is 90% after 4 hours and 57% after 24 hours.
The use of levocetirizine at a dose of 5 mg significantly reduces the formation of urticarial elements (blisters) in the first 12 hours, this effect lasts up to 24 hours, compared with placebo and desloratadine.
Pharmacokinetics
The pharmacokinetic parameters of levocetirizine change linearly.
Suction
After oral administration, the drug is quickly and completely absorbed from the gastrointestinal tract. Eating does not affect the completeness of absorption, although it reduces its speed. The maximum concentration (Cmax) in blood plasma is reached after 0.9 hours and is 270 ng/ml, the equilibrium concentration is achieved after 2 days.
After taking 5 mg Allerway Express tablets by healthy volunteers on an empty stomach, levocetirizine was detected in the blood after 24 hours at a concentration exceeding 10% of Cmax.
Distribution
Levocetirizine is 90% bound to plasma proteins. The volume of distribution (Vd) is 0.4 l/kg. Bioavailability reaches 100%.
Metabolism
In small quantities (less than 14%), levocetirizine is metabolized in the body by N- and O-dealkylation (unlike other H1-histamine receptor antagonists, which are metabolized in the liver using the cytochrome system) to form a pharmacologically inactive metabolite. Due to negligible metabolism and lack of metabolic potential, interaction of levocetirizine with other drugs is unlikely.
Removal
The half-life (T1/2) in adults is 7.9±1.9 hours. In young children, T1/2 is shorter. In adults, the total clearance is 0.63 ml/min/kg.
About 85.4% of the administered dose of the drug is excreted unchanged by the kidneys through glomerular filtration and tubular secretion; about 12.9% - through the intestines.
Selected patient groups
Patients with kidney failure
In patients with renal failure (creatinine clearance (CC)
Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.
Patients with liver failure
The pharmacokinetics of levocetirizine in patients with hepatic impairment have not been studied. In patients with chronic liver diseases (hepatocellular, cholestatic and biliary cirrhosis) receiving the racemic compound cetirizine at a dose of 10 mg or 20 mg once, there was an increase in T1/2 by 50% and a decrease in drug clearance by 40%, compared with healthy people.
Children
Data from a study of the pharmacokinetics of the drug in 14 children aged 6 to 11 years with a body weight of 20 to 40 kg with a single oral dose of 5 mg of levocetirizine showed that Cmax values and the area under the pharmacokinetic concentration-time curve (AUC) were approximately twice as high as those in healthy adults when cross-checked. The average Cmax was 450 ng/ml, the maximum concentration was reached on average after 1.2 hours, the total clearance taking into account body weight was 30% higher, and T1/2 was 24% shorter in children than the corresponding values in adults. Specific pharmacokinetic studies have not been conducted in children under 6 years of age. A retrospective pharmacokinetic analysis was conducted in 323 patients (181 children aged 1 to 5 years, 18 children aged 6 to 11 years, and 124 adults aged 18 to 55 years) who received one or more doses of levocetirizine 1.25 mg. up to 30 mg. Data obtained during the analysis showed that taking the drug at a dose of 1.25 mg in children aged 6 months to 5 years leads to plasma concentrations similar to those in adults when taking 5 mg of the drug once a day.
Elderly patients
Pharmacokinetic data in elderly patients is limited. When repeated dosing of levocetirizine 30 mg once daily for 6 days in 9 elderly patients (ages 65 to 74 years) total clearance was approximately 33% lower than that in younger adults. The distribution of cetirizine racemate has been shown to be more dependent on renal function than on age. This statement may also apply to levocetirizine, since both drugs - levocetirizine and cetirizine - are eliminated primarily by the kidneys.
Therefore, in elderly patients, the dose of levocetirizine should be adjusted depending on renal function.
Ketorol express tablets dispersible in the oral cavity 10 mg No. 20
Interaction
The simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to a significant increase in the risk of adverse reactions, including the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.
When ketorolac is used simultaneously with other NSAIDs (including COX-2 inhibitors), fluid retention, cardiac decompensation, and increased blood pressure may occur.
Concomitant use of ketorolac with indirect anticoagulants, thrombolytics, antiplatelet agents, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding. Probenecid reduces the plasma clearance and volume of distribution of ketorolac, increases its concentration in the blood plasma and increases its T1/2.
The combined use of ketorolac with valproate causes disruption of platelet aggregation. When using ketorolac with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases.
Combined use with paracetamol increases the nephrotoxicity of ketorolac.
Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in the blood plasma.
The combined use of ketorolac with methotrexate increases the hepato- and nephrotoxicity of methotrexate.
The combined use of ketorolac and methotrexate is possible only when using low doses of the latter. The clearance of methotrexate may decrease (it is necessary to monitor the concentration of methotrexate in the blood plasma). With the use of ketorolac, it is possible to reduce the clearance of lithium, increase its concentration in the blood plasma and increase the toxic effect of lithium.
Simultaneous use with lithium salts is contraindicated. Ketorolac reduces the effect of antihypertensive and diuretic drugs (the synthesis of prostaglandins in the kidneys is reduced). Ketorolac enhances the effect of narcotic analgesics.
When combined with opioid analgesics, the doses of the latter can be significantly reduced. Ketorolac enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs, and therefore it is necessary to recalculate the dose of these drugs. Ketorolac increases the plasma concentrations of verapamil and nifedipine.
Concomitant use of NSAIDs and mifepristone may reduce the effectiveness of mifepristone. NSAIDs are not recommended for use within 8-12 days after using mifepristone.
Concomitant use of NSAIDs and cyclosporine increases the risk of nephrotoxicity.
The simultaneous use of NSAIDs and quinolone antibiotics increases the risk of developing seizures.
Concomitant use of NSAIDs and tacrolimus increases the risk of nephrotoxicity.
Concomitant use of NSAIDs and zidovudine increases the risk of hematological toxicity.
When used simultaneously with digoxin, ketorolac does not interfere with the binding of digoxin to plasma proteins.
Therapeutic concentrations of digoxin do not affect the binding of ketorolac to plasma proteins.
Antacids do not affect the absorption of ketorolac. Myelotoxic drugs increase the manifestations of hematotoxicity of ketorolac.
Zodac® Express
The pharmacokinetic parameters of levocetirizine change linearly and practically do not differ from the pharmacokinetics of cetirizine.
Suction
After oral administration, the drug is quickly and completely absorbed from the gastrointestinal tract. Eating does not affect the completeness of absorption, although its speed decreases. In adults, after a single dose of the drug in a therapeutic dose (5 mg), the maximum concentration (Cmax) in the blood plasma is reached after 0.9 hours and is 270 ng/ml, after a repeated dose of 5 mg - 308 ng/ml. Equilibrium concentration is achieved after 2 days.
Distribution
Levocetirizine is 90% bound to plasma proteins. The volume of distribution (Vd) is 0.4 l/kg. Bioavailability reaches 100%.
Metabolism
In small amounts (<14%), levocetirizine is metabolized in the body by N- and O-dealkylation (unlike other H1-histamine receptor antagonists, which are metabolized in the liver via the cytochrome system) to form a pharmacologically inactive metabolite.
Due to negligible metabolism and lack of metabolic potential, interaction of levocetirizine with other drugs is unlikely.
Removal
In adults, the half-life (T1/2) is 7.9 ± 1.9 hours; in young children T1/2 is shortened. In adults, the total clearance is 0.63 ml/min/kg. About 85.4% of the administered dose of the drug is excreted unchanged by the kidneys through glomerular filtration and tubular secretion; about 12.9% - through the intestines.
Pharmacokinetics in special groups of patients
Patients with kidney failure
In patients with renal failure (creatinine clearance (CC) < 40 ml/min), the clearance of the drug is reduced and T1/2 is prolonged (for example, in patients on hemodialysis, the total clearance is reduced by 80%), which requires a corresponding change in the dosage regimen. Less than 10% of levocetirizine is removed during a standard 4-hour hemodialysis procedure.
Children
Data from a study of the pharmacokinetics of the drug in 14 children aged 6 to 11 years weighing from 20 to 40 kg with a single oral dose of 5 mg of levocetirizine showed that Cmax and area under the curve (AUC) were approximately twice as high as in healthy adults with cross-control. The mean Cmax was 450 ng/ml, the maximum concentration was reached after an average of 1.2 hours, the total body weight-adjusted clearance was 30% higher, and the half-life was 24% shorter in children than in adults. A retrospective pharmacokinetic analysis was conducted in 324 patients (children aged 1 to 11 years and adults aged 18 to 55 years) who received one or more doses of levocetirizine from 1.25 mg to 30 mg. Data obtained during the analysis showed that taking the drug at a dose of 1.25 mg in children under 5 years of age leads to plasma concentrations corresponding to those in adults when taking 5 mg of the drug once a day.
Elderly patients
Pharmacokinetic data in elderly patients is limited. When repeated dosing of levocetirizine 30 mg once daily for 6 days in elderly patients (age 65 to 74 years) total clearance was approximately 33% lower than that in younger adults. The distribution of cetirizine racemate has been shown to be more dependent on renal function than on age. This statement may also apply to levocetirizine, since both levocetirizine and cetirizine are excreted primarily in the urine. Therefore, in elderly patients, the dose of levocetirizine should be adjusted depending on renal function.
