Does Citrine Have Side Effects?
Release form, packaging and composition of the drug Cetrin ®
White or almost white, film-coated tablets, round, biconvex, scored on one side; On a cross section, the core is white to almost white.
| 1 table. | |
| cetirizine dihydrochloride | 10 mg |
Excipients: lactose, corn starch, povidone (K-30), magnesium stearate. Film shell composition: hypromellose, macrogol 6000, titanium dioxide, talc, sorbic acid, polysorbate 80, dimethicone. 10 pieces. – blisters (2) – cardboard packs.
10 pieces. – blisters (3) – cardboard packs.
pharmachologic effect
A competitive histamine antagonist, a metabolite of hydroxyzine, blocks H1-histamine receptors. Prevents the development and facilitates the course of allergic reactions, has antipruritic and antiexudative effects. Affects the early stage of allergic reactions, limits the release of inflammatory mediators at the “late” stage of the allergic reaction, reduces the migration of eosinophils, neutrophils and basophils. Reduces capillary permeability, prevents the development of tissue edema, relieves spasm of smooth muscles. Eliminates skin reactions to the introduction of histamine, specific allergens, as well as to cooling (with cold urticaria). Reduces histamine-induced bronchoconstriction in mild bronchial asthma. It has virtually no anticholinergic and antiserotonin effects. In therapeutic doses it has virtually no sedative effect. The onset of the effect after a single dose of 10 mg of cetirizine is 20 minutes, the duration of the effect is 24 hours. During the course of treatment, tolerance to the antihistamine effect of cetirizine does not develop. After stopping treatment, the effect lasts up to 3 days.
Pharmacokinetics
The pharmacokinetic parameters of cetirizine change linearly when administered at a dose of 5–60 mg. After oral administration, it is quickly absorbed from the gastrointestinal tract, Tmax after oral administration is about 1 hour. Food does not affect the completeness of absorption (AUC), but prolongs Tmax by 1 hour and reduces Cmax by 23%. When taken at a dose of 10 mg 1 time/day for 10 days, C ss in plasma is 310 ng/ml and is observed 0.5-1.5 hours after administration. Plasma protein binding is 93% and does not change at cetirizine concentrations in the range of 25-1000 ng/ml. Vd – 0.5 l/kg. In small quantities, it is metabolized in the liver by O-dealkylation to form a pharmacologically inactive metabolite (unlike other histamine H1 receptor blockers, which are metabolized in the liver with the participation of isoenzymes of the cytochrome P 450 system. Cetirizine does not accumulate. About 2/3 of the drug is excreted unchanged by the kidneys and about 10% in the feces. Systemic clearance – 53 ml/min. T1/2 in adults – 10 hours, in children 6-12 years old – 6 hours, 2-6 years old – 5 hours, 0,5-2 years old – 3,1 hours. In elderly patients, T1/2 increases by 50 %, systemic clearance is reduced by 40% (decreased renal function). Pharmacokinetics in special clinical situations In patients with impaired renal function (creatinine clearance below 40 ml/min), the clearance of the drug decreases, and T1/2 is prolonged (for example, in patients on hemodialysis, the total clearance decreases by 70% and is 0.3 ml/min/kg, and T 1/2 is extended by 3 times), which requires a corresponding change in the dosage regimen. It is practically not removed during hemodialysis. In patients with chronic liver diseases (hepatocellular, cholestatic or biliary cirrhosis), there is an increase in T1/2 by 50% and a decrease in total clearance by 40% (adjustment of the dosage regimen is required only with a concomitant decrease in glomerular filtration rate). Passes into breast milk.
Indications for the drug Cetrin ®
- seasonal and year-round allergic rhinitis;
- allergic conjunctivitis;
- hay fever (hay fever);
- urticaria (including chronic idiopathic urticaria);
- itchy allergic dermatoses (atopic dermatitis, neurodermatitis);
- angioedema (Quincke’s edema).
| Code IKB-10 | Indication |
| H10.1 | Acute atopic (allergic) conjunctivitis |
| J30.1 | Allergic rhinitis caused by pollen |
| J30.3 | Other allergic rhinitis (perennial allergic rhinitis) |
| L20.8 | Other atopic dermatitis (neurodermatitis, eczema) |
| L23 | Allergic contact dermatitis |
| L24 | Simple irritant contact dermatitis |
| L28.0 | Lichen simplex chronicus (limited neurodermatitis) |
| L29 | Itching |
| L30.0 | Coin eczema |
| L50 | Hives |
| T78.3 | Angioedema (Quincke’s edema) |
Each tablet contains: active substance: cetirizine hydrochloride -10 mg;
vspomogatelnye veshchestva: anhydrous lactose, corn starch, povidone (K-30), magnesium stearate, tablet shell (including hypromellose, sorbic acid, titanium dioxide (E171), purified talc, macrogol 6000, polysorbate 80, dimethicone).
Description
Film-coated tablets are white or almost white, round, with a biconvex surface, one side is smooth, the other has a dividing line. The tablet can be divided into equal doses.
Pharmacotherapeutic group
Antihistamines for systemic use, piperazine derivatives.
Code ATX: R06AE07
Pharmacological properties
Pharmacodynamics
Mechanism of action
Cetirizine, a metabolite of hydroxyzine, is a powerful selective antagonist of peripheral H1 receptors with virtually no effect on other receptors.
In addition to blocking peripheral H1 receptors, cetirizine has antiallergic properties. When used in a dose of 10 mg 1 or 2 times a day, the drug suppresses the accumulation of eosinophils in the skin and conjunctiva in the late phase in patients suffering from atopy after provocation by an allergen.
Clinical efficacy and safety
Studies conducted in healthy volunteers have shown that cetirizine at a dose of 5 mg or 10 mg significantly reduces the “triple response” – a skin reaction like “bloom” caused by high concentrations of histamine in the skin, however, this effect is correlated with clinical effectiveness not proven.
One 35-day study in children aged 5-12 years showed no development of tolerance, i.e. inability to suppress the “bloom” response to the antihistamine effect of cetirizine. After discontinuation of repeated doses of cetirizine for three days, the skin regained its characteristic ability to respond to histamine.
The 6-week, placebo-controlled study involved 186 patients with allergic rhinitis and concomitant mild to moderate asthma. Cetirizine at a dose of 10 mg/day alleviated the symptoms of rhinitis and did not affect respiratory function. This study confirmed the safety of cetirizine in allergy patients with mild to moderate asthma.
One placebo-controlled study showed that high-dose cetirizine (60 mg/day) for 7 days did not significantly prolong the QT interval.
Based on the studies conducted, it was found that cetirizine in recommended doses improves the quality of life of patients suffering from persistent or seasonal allergic rhinitis.
Pharmacokinetics
Suction
The equilibrium maximum concentration is approximately 300 ng/ml and is achieved within 1.0±0.5 hours. Cetirizine at a dose of 10 mg/day did not accumulate when repeated dosing for 10 days. Distribution of pharmacokinetic parameters such as maximum plasma concentration (Cmax) and area under the curve (AUC), is unimodal.
Food does not affect the completeness of absorption, although the rate of absorption decreases. The degree of bioavailability is similar when cetirizine is used in the form of solution, capsules or tablets.
Distribution
The apparent volume of distribution is approximately 0.50 l/kg. 93±0.3% of cetirizine is bound to plasma proteins. Cetirizine does not affect the binding of warfarin to plasma proteins.
Biotransformation
Cetirizine does not undergo significant pre-systemic metabolism.
Excretion
About 2/3 of the dose is excreted unchanged in the urine. The half-life is approximately 10 hours.
Linearity/nonlinearity
Cetirizine has linear kinetics in the dose range from 5 to 60 mg.
Special patient groups
Elderly
In 16 elderly volunteer subjects, following a single oral dose of 10 mg cetirizine, the elimination half-life was increased by approximately 50% and clearance was decreased by 40% compared with non-elderly subjects. The decreased clearance of cetirizine in these elderly volunteers was likely due to worsening renal function.
Children and babies
The half-life of cetirizine was approximately 6 hours in children aged 6 to 12 years and 5 hours in children aged 2 to 6 years. In children aged 6 to 24 months, the half-life was reduced to 3.1 hours.
Patients with impaired renal function
In patients with mild renal failure (creatinine clearance>40 ml/min), the pharmacokinetics of the drug were similar to those in healthy volunteers. In moderate renal failure, compared with healthy volunteers, the half-life increased threefold and clearance decreased by 70%.
Compared with healthy volunteers, hemodialysis patients (HD)
Indications for use
For adults and children 6 years and older:
• relief of symptoms of seasonal and year-round allergic rhinitis (hay fever, hay fever); the maximum duration of treatment for seasonal rhinitis in children is 4 weeks;
• allergic conjunctivitis;
• chronic idiopathic urticaria.
Противопоказания
• hypersensitivity to cetirizine, hydroxyzine or piperazine derivatives, as well as other components of the drug;
• end-stage renal failure (creatinine clearance
Dosing and Administration
Seasonal allergic rhinitis
Adults and teenagers over 12 years of age: The recommended dose is 10 mg (1 tablet) 1 time per day.
Deti ot 6 do 12 let: 10 mg (1 tablet) 1 time per day. The maximum duration of treatment is 4 weeks.
The dose can be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening, respectively.
Allergic Conjunctivitis
Adults and teenagers over 12 years of age: The recommended dose is 10 mg (1 tablet) 1 time per day.
Deti ot 6 do 12 let: 10 mg (1 tablet) 1 time per day. The maximum duration of treatment is 4 weeks. The dose can be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening, respectively.
Perennial allergic rhinitis and chronic idiopathic urticaria
Adults and teenagers over 12 years of age: The recommended dose is 10 mg (1 tablet) 1 time per day.
Deti ot 6 do 12 let: 10 mg (1 tablet) 1 time per day. The dose can be divided into 2 doses of 5 mg (1/2 tablet) in the morning and evening, respectively.
Patients requiring special dosing regimens
Elderly patients
With an age-related decrease in glomerular filtration, the drug is prescribed for elderly patients at the same dose as for patients with renal failure.
Patients with kidney failure
There are no data on the effectiveness and safety of cetirizine in patients with renal failure. Because cetirizine is primarily eliminated by the kidney, in cases where alternative treatment cannot be used, dosing intervals should be individualized according to renal function.
The intervals between taking the drug are individually adjusted depending on the degree of renal failure. Dosing is carried out in accordance with the table below. When using this table, creatinine clearance (CC) is calculated in ml/min.
Creatinine clearance can be calculated from serum creatinine concentration (mg/dL) using the following formula:
CC for women can be calculated by multiplying the resulting value by a factor of 0,85.
Dosing for patients with renal impairment
Side effect
According to clinical studies, cetirizine at all recommended doses can cause only minimal adverse reactions from the central nervous system, such as drowsiness, fatigue, dizziness and headache. In some cases, paradoxical stimulation of the central nervous system was observed.
Although cetirizine is a selective peripheral H1 receptor antagonist and has relatively no anticholinergic activity, urinary and visual accommodation disturbances, as well as dry mouth, have been observed in isolated cases.
There have been cases of liver dysfunction with elevated liver enzymes accompanied by elevated bilirubin levels. In most cases, these changes resolve when treatment with cetirizine is discontinued.
Clinical researches
Double-blind, controlled clinical or pharmacoclinical studies of cetirizine compared with placebo or other antihistamines at recommended doses (for cetirizine 10 mg/day) for which quantitative safety data were available included 3200 patients treated with cetirizine.
Based on these placebo-controlled study data pooled together, the following adverse reactions were observed for cetirizine 10 mg, occurring at an incidence of 1% or more:
Adverse reaction (WHO-ART)
Cetirizine 10 mg (n=3260)
Despite a statistically higher incidence of somnolence compared to placebo, in most cases the severity of somnolence was mild to moderate. Data from objective tests conducted in other studies showed that daily activities were not impaired in young healthy volunteers when the drug was used at recommended doses.
Children and adolescents
Adverse reactions observed with an incidence of 1% or greater in clinical or pharmacoclinical studies in children aged 6 months to 12 years are listed below:
| Adverse reaction (WHO-ART) | Cetirizine (n=1656) | Placebo (n= 1294) |
| Gastrointestinal disorders Diarrhea | 1.0% | 0.6% |
| Mental disorders Drowsiness | 1.8% | 1.4% |
| Respiratory system disorders Rhinitis | 1.4% | 1.1% |
| General disorders Fatigue | 1.0% | 0.3% |
To describe side effects, the following categories of frequency of occurrence were used depending on the total number of cases of use: very often (≥1/10), often (≥1/100,
Safety measures
• In patients with renal insufficiency, the dose should be adjusted accordingly (see section “Dosage and Administration”).
• In elderly patients, renal function may decrease, which should be taken into account when dosing the drug.
• The use of Cetrin in patients with epilepsy and a tendency to seizures should be carried out with caution.
• In children under 6 years of age, the use of film-coated tablets is not recommended, since the release form does not allow for dose adjustment of the drug.
• When taking Cetrin, you should avoid drinking alcohol and CNS antidepressants, as cetirizine may cause increased drowsiness.
• Caution should be exercised in patients who have predisposing factors for urinary retention (spinal cord lesions, prostatic hyperplasia), since cetirizine may increase the risk of urinary problems.
Influence on the ability to manage transport means and work mechanisms
The use of the drug may cause drowsiness, so persons driving vehicles and working with machinery should not exceed the recommended dose.
Objective measurements of driving ability, sleep latency, and work performance did not demonstrate any clinically significant effects at the recommended dose of 10 mg.
Patients should consider their own response to the drug. In the central nervous system, it may lead to further decreased vigilance and decreased performance.
Application in pregnancy and lactation
Pregnancy
There are currently no clinical studies available on the use of cetirizine in pregnant women. Experimental studies on animals did not reveal any direct or indirect toxic effect of cetirizine on the course of pregnancy, embryonic development, embryonic development, including in the postnatal period. The potential risk for women is unknown. Caution should be exercised when taking the drug during pregnancy.
Lactation
Cetirizine is excreted in breast milk, so the drug should be prescribed with caution during breastfeeding.
Interaction with other drugs
When used simultaneously with pseudoephedrine, cimetidine, ketoconazole, erythromycin or azithromycin, no effect on the pharmacokinetics of cetirizine was detected. No pharmacodynamic interactions were observed. Tests in vitro showed that cetirizine does not affect the protein binding properties of warfarin.
When used simultaneously with azithromycin, erythromycin, ketoconazole, theophylline and pseudoephedrine, no clinically significant undesirable interactions were identified, and no changes were noted in the electrocardiogram.
With simultaneous use of cetirizine (20 mg/day) with theophylline (400 mg/day), a small but stable increase in the area under the concentration-time curve per day was detected, cetirizine by 19%, theophylline -11%. Moreover, the maximum plasma levels reached 7,7% and 6,4% for cetirizine and theophylline, respectively. At the same time, the total clearance of cetirizine decreased by 16%, the clearance of theophylline by 10%, if treatment with theophylline was carried out before the administration of cetirizine. However, when treated initially with cetirizine, no significant effect on the pharmacokinetics of theophylline was detected.
After a single dose of 10 mg of cetirizine, the effect of alcohol is not significantly enhanced; 1 of 16 psychometric tests showed a statistically significant interaction with diazepam 5 mg.
With simultaneous daily use of cetirizine (10 mg) with glipizide, the blood glucose concentration decreased slightly. However, this was not clinically significant. However, it is recommended to take these medications separately – glipizide in the morning and cetirizine in the evening.
Eating does not affect the completeness of absorption, although its rate decreases by 1 hour.
With repeated dosing of ritonavir (600 mg twice daily) and cetirizine (10 mg/day), the effect rate increased by 40%, while the effect of ritonavir changed little (-11%) with concomitant use of cetirizine.
A three-day washout period is recommended before prescribing allergy tests. Antihistamines have an inhibitory effect on skin allergy tests.
Overdose
Symptoms observed after cetirizine overdose are mainly related to CNS effects or effects that may indicate an anticholinergic effect.
With a single dose of 50 mg, the following were observed: symptoms: confusion, diarrhea, dizziness, fatigue, headache, malaise, mydriasis, itching, weakness, anxiety, sedation, drowsiness, stupor, tachycardia, tremor, urinary retention.
Treatment: immediately after taking the drug – gastric lavage or inducing vomiting. It is recommended to take activated carbon and carry out symptomatic and supportive therapy. There is no specific antidote. Hemodialysis is ineffective.
Packaging
10 tablets in a blister pack made of PVC/PVDC film and aluminum foil. 2 blister packs together with instructions for medical use are placed in a cardboard pack (No. 10×2).
Storage conditions
Store in a place protected from light and moisture, at temperatures up to 25°C. Keep out of the reach of children.
Shelf life
3 years. Do not use after the expiration date stated on the package.
Conditions for dispensing from pharmacies
Information about manufacturer
Manufactured and packaged by: Dr. Reddy’s Laboratories Ltd., India.
Packed: open joint-stock company “Borisov Medical Preparations Plant”, Republic of Belarus, Minsk region, Borisov, st. Chapaeva, 64, tel/fax +375(177)735612
