Zestra

Zestra is a systemic antihistamine drug whose active ingredient is cetirizine.

Indications Zestra

It is indicated for the treatment of rhinitis, as well as allergic conjunctivitis (regular or seasonal), and also recurrent urticaria (chronic stage).

Release form

Available in tablet form, 10 pieces per blister. One package contains 1 blister plate.

Pharmacodynamics

Zestra is a combination drug, its properties are determined by the action of the components included in its composition.

Cetirizine hydrochloride is a 2nd generation antihistamine, a selective receptor blocker (H1); has a prolonged effect. It also has weak anticholinergic properties, does not interact with dopamine and serotonin receptors, as well as H2 and α-adrenergic receptors.

The pronounced synthesis with plasma protein, as well as the polarity of cetirizine, are the reason that it poorly passes through the BBB and has almost no suppressive effect on the central nervous system - this is what distinguishes this drug from 1st generation antihistamines. Such properties are mainly the result of its lipophilicity.

The active component affects the early histamine-dependent stage of development of allergic manifestations, and in addition, inhibits the processes of histamine release from basophilic leukocytes with fat cells, and reduces the frequency of movement of inflammatory cells that are participants in allergic responses (slows down the movement of eosinophils and inhibits the processes of release of inflammatory conductors from mast cells). It also weakens the effect of conductors of the allergic response (histamine and PG D2), and at the same time inhibits the movement of eosinophils in people with atopic reactions. In addition, it reduces histamine-induced bronchoconstriction (in the presence of bronchial asthma) and provokes a long-term selective effect on receptors (H1).

The medicinal effect begins 2 hours after consumption and lasts for 24 hours.

Pseudoephedrine hydrochloride is a β-agonist with vasoconstrictor properties. It reduces swelling of the mucous membrane of the upper respiratory tract (especially the paranasal sinuses and nasopharynx) during symptomatic therapy of infectious-inflammatory and allergic pathologies in this area.

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Pharmacokinetics

The active ingredient is rapidly absorbed from the gastrointestinal tract. Peak serum concentration at steady state is 300 ng/ml (observed 0.5-1 hour after ingestion). When administered on an empty stomach, approximately 70% of the substance is absorbed. Food intake does not affect the volume of absorption, but slows down the rate of this process. Peak medicinal effect begins after 4-8 hours and lasts for about 24 hours. Approximately 93% of the active ingredient is synthesized with plasma protein.

The distribution volume is 0.56-0.8 l/kg (adults) and 0.7 l/kg (children). The substance is partially metabolized. With daily administration of 10 mg of the drug for 10 days, accumulation of cetirizine was not detected.

Approximately 60% of the dosage is excreted in urine over the next 24 hours, and then about 10% of the substance is excreted in the same way over the next 4 days. In children, only 40% of the drug is excreted in 24 hours. Over 5 days, about 10% of the dosage (including as a decay product) is excreted in feces.

The half-life of the active ingredient is 7.4 hours. In case of renal failure in the patient, elimination will be slower. In case of mild renal dysfunction, this period sometimes increases to 19-21 hours.

The coefficient of purification of the substance in the kidneys is 70 ml/minute (with healthy kidney function), but if there are mild impairments of function, this figure is 7 ml/minute; with moderate impairment – 1.5 ml/minute. Hemodialysis is not suitable for eliminating the component.

Pseudoephedrine hydrochloride is absorbed fairly quickly through the digestive tract, beginning to act within half an hour of taking the medication. In general, its effect lasts for 4 hours.

Partial metabolism of pseudoephedrine occurs through the liver via N-demethylation, converting it into the active breakdown product norpseudoephedrine.

The pseudoephedrine component, together with its breakdown products, is excreted in the urine; approximately 55-75% of a single dose is excreted unchanged. The rate of excretion of the substance increases in the case of urine oxidation, and, on the contrary, decreases in the case of its alkalization.

The half-life is 7 hours. A small portion of pseudoephedrine passes into breast milk (about 0.5-0.7% of a single dose of the drug taken by the mother passes into the milk within 24 hours).

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Dosing and administration

The medicine is taken orally. For children over 12 years old and adults, the dosage is 1 tablet per day, washed down with water. The duration of the course is prescribed by the attending physician - it depends on the severity of the pathology, as well as the patient's condition.

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Use Zestra during pregnancy

The medicine is prohibited to be prescribed to pregnant women, as well as during lactation.

Contraindications

Among the contraindications:

• intolerance to the components of the drug;
• severe renal dysfunction (creatinine clearance less than 10-10 ml/minute);
• insomnia;
• uncontrolled increase in blood pressure, as well as tachycardia;
• obstructive form of HCM;
• IHD;
• the patient has pheochromocytoma, hyperthyroidism or diabetes mellitus;
• severe forms of liver pathologies;
• ventricular fibrillation;
• use of MAO inhibitors in the period preceding 2 weeks of drug use;
• age under 12 years.

Side effects Zestra

The use of drugs can cause the following side effects:

• Digestive system organs: weight gain, dyspepsia, taste disturbance and taste retardation; anorexia, stomatitis, gastritis, diabetes mellitus and liver dysfunction (increased activity of liver enzymes, Y-glutamyl transferase, and alkaline phosphatase; and also increased activity of the bilirubin component in the blood) occasionally develop. In addition, dry mouth, thirst, swelling and discoloration of the tongue, nausea, bloating, abdominal pain, and vomiting occasionally appear;
• organs of the nervous system: a feeling of drowsiness and dizziness; occasionally headaches, tremor with migraine, hyperesthesia and hyperesthesia with paresthesia, seizures and fainting, as well as excessive aggressiveness, asthenia, confusion, a feeling of excitement or malaise, depression, severe fatigue, insomnia and the appearance of hallucinations develop;
• cardiovascular system: dystonia, tachycardia and increased blood pressure appear occasionally;
• organs of the hematopoietic system: development of thrombocytopenia;
• visual organs: blurred vision, as well as accommodation disorder and involuntary eye movements;
• respiratory organs: nosebleeds, runny nose with cough, bronchial spasms, development of pharyngitis, pneumonia, bronchitis and dysphonia;
• immune system organs: rashes and itching, as well as urticaria; edema, allergic reactions, anaphylaxis and Quincke's edema are observed sporadically;
• bone structure and muscles: arthritis, muscle and joint pain, muscle weakness and dyskinesia;
• urinary system: dysuria, problems with urination, and enuresis.

Side effects caused by pseudoephedrine hydrochloride:

• cardiovascular system: development of brady-, steno- or tachycardia, problems with heartbeat, increase/decrease in blood pressure, appearance of edema, heart failure, arrhythmia, as well as chest pain;
• organs of the nervous system: dizziness and headaches, anxiety, nervousness, agitation, development of tremor and emotional lability. In addition to this, disorders of thinking or attention, as well as psychoneurological disorders (memory problems, disorientation, development of psychomotor agitation, panic or aggression, paranoia, schizophrenic disorders, as well as the appearance of hallucinations (all this is due to the central effect of pseudoephedrine), along with this - a state of insomnia, sleep disorders, the appearance of convulsions and muscle twitching, hyperkinesis, feelings of euphoria or amnesia, and in addition, a state of depression);
• digestive system: increased appetite, constipation, increased salivation, nausea, bloating, abdominal pain, vomiting, diabetes and liver dysfunction;
• genitourinary system: pain or difficulty when urinating (in case of prostate hyperplasia), as well as its delay, development of cystitis, polyuria, pyelitis, hematuria or dysuria. In addition, the appearance of vaginitis or dysmenorrhea, as well as decreased libido;
• allergic manifestations: development of erythema multiforme;
• sensory organs: pain in the eyes or hemorrhage in them, visual disturbances, the appearance of tinnitus or glaucoma, the development of deafness, ptosis and xerophthalmia;
• Others: chills, weakness, fever, hypokalemia or lymphadenopathy, and increased sweating. These symptoms disappeared after discontinuation of the drug.

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Overdose

Overdose symptoms are usually associated with the effect on the central nervous system or are caused by the anticholinergic properties of the drug. Among them are: a feeling of embarrassment, dizziness, psychoemotional agitation, a feeling of irritation, nervousness, and in addition, severe fatigue, drowsiness or insomnia, severe headaches and a state of stupor. In addition, there are delays in urination, circulatory disorders, and increased sweating. Along with this, convulsions, tremors, tachycardia and trembling of the limbs may occur. Loss of appetite, vomiting, dry mouth, nausea and diarrhea, increased blood pressure, itching with rashes and mydriasis are also possible.

To get rid of these symptoms, the patient needs to wash out the stomach and then take enterosorbents.

In addition, to eliminate the above-described manifestations, methods are used to correct the work of the cardiovascular system, as well as support the external respiratory process. If necessary, anticonvulsants are used and catheterization of the bladder is performed. An effective option for accelerating the elimination of pseudoephedrine is the dialysis procedure or acidification of urine. There is no specific antidote.

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Interactions with other drugs

The active component of Zestra does not interact with other drugs (such as cimetidine, pseudoephedrine, as well as erythromycin with ketoconazole and diazepam with azithromycin). In case of use with large amounts of alcohol (blood concentration index greater than 0.8 ‰), suppression of the central nervous system function is possible. It is necessary to combine with caution with drugs that suppress the central nervous system.

Combined use with drugs that have an ototoxic effect (such as gentamicin) can mask the manifestations of ototoxicity (dizziness and tinnitus).

Concomitant administration with theophylline (daily dosage – 400 mg once) reduces the cetirizine clearance coefficient (-16%), but no changes were observed in the elimination of theophylline.

In case of using Zestra (due to the presence of pseudoephedrine in its composition), it is necessary to refuse other sympathomimetics (such as mezaton or naphthyzine), tricyclics (including imipramine with amitriptyline), anorexic drugs (mazindol with desopimone), MAO inhibitors (pyrazidole with nialamide) and furazolidone - with such a combination, blood pressure levels can increase sharply.

Pseudoephedrine can weaken the effect of sympatholytics (such as octadine with reserpine), as well as β-adrenergic receptor blockers (including pindolol with nadolol).

In the case of a combination of pseudoephedrine and levodopa, as well as cardiac glycosides, the likelihood of developing severe ventricular arrhythmias increases.

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Storage conditions

The medicine must be kept in a place protected from moisture and sun, inaccessible to small children. The storage temperature should not exceed 25 ^o C.

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Shelf life

Zestra is suitable for use within 3 years from the date of manufacture of the medicine.