Instructions for use Acyclovir-Darnitsa tablets 200 mg No. 20
Composition
active ingredient: aciclovir;
1 tablet contains acyclovir 200 mg;
Excipients: potato starch, povidone, croscarmellose sodium, calcium stearate.
Dosage form
Pills.
Main physicochemical properties: white or almost white tablets with a bevel and a score.
Pharmacotherapeutic group
Antiviral agents for systemic use.
ATX code J05A B01.
Pharmacological properties
Pharmacodynamics.
Acyclovir is a synthetic purine nucleoside analogue with in vivo and in vitro inhibitory activity against human herpesviruses, including herpes simplex virus types I and II, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus. In cell culture, acyclovir exhibits the greatest activity against herpes simplex virus type I and then, in decreasing order of activity, against herpes simplex virus type II, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus.
The inhibitory activity of acyclovir against the above viruses is highly selective. The enzyme thymidine kinase in a normal uninfected cell does not use acyclovir as a substrate, so the toxic effect on host cells is minimal. However, thymidine kinase, encoded by herpes simplex viruses, varicella zoster viruses, and Epstein-Barr virus, converts acyclovir to acyclovir monophosphate, a nucleoside analogue, which is then converted sequentially to diphosphate and triphosphate by cellular enzymes. Following incorporation into viral DNA, acyclovir triphosphate interacts with viral DNA polymerase, resulting in termination of viral DNA chain synthesis.
With prolonged or repeated courses of treatment of severely immunocompromised patients, a decrease in the sensitivity of individual strains of the virus is possible, which do not always respond to treatment with acyclovir. Most clinical cases of insensitivity are associated with a deficiency of viral thymidine kinase, but there are reports of damage to viral thymidine kinase and DNA. In vitro interaction of individual herpes simplex viruses with acyclovir can also lead to the formation of less sensitive strains. The relationship between the sensitivity of individual herpes simplex viruses in vitro and the clinical results of treatment with acyclovir is not fully understood.
Pharmacokinetics.
Acyclovir is only partially absorbed from the gastrointestinal tract (approximately 20% of the dose). Simultaneous food intake does not lead to a decrease in absorption. The maximum concentration is reached after 1.5-2 hours.
Its level of binding to blood plasma proteins is relatively low (from 9% to 33%) and does not change when interacting with other drugs.
Acyclovir penetrates the placental barrier, into cerebrospinal fluid (50% of the corresponding concentration in blood plasma), and breast milk.
Most of the drug (85-90%) is excreted unchanged by the kidneys and only a small part (10-15%) is excreted as a metabolite (9-carboxymethoxymethylguanine). Renal clearance of acyclovir is significantly higher than creatinine clearance, which indicates that renal excretion of the drug is carried out not only by glomerular filtration, but also by tubular secretion.
The terminal half-life of intravenous acyclovir is approximately 2.9 hours, in patients with chronic renal failure - 19.5 hours, during hemodialysis - 5.7 hours. The level of acyclovir in blood plasma during dialysis decreases by approximately 60%.
Indication
Treatment of infections of the skin and mucous membranes caused by the Herpes simplex virus, including primary and recurrent genital herpes.
Prevention of recurrence of infections caused by the Herpes simplex virus in patients with normal immunity.
Prevention of infections caused by the Herpes simplex virus in immunocompromised patients.
Treatment of infections caused by the Varicella zoster virus (chickenpox, shingles).
Contraindication
Hypersensitivity to acyclovir, valacyclovir or other components of the drug.
Interaction with other medicinal products and other types of interactions
Acyclovir is excreted mainly unchanged by the kidneys by tubular secretion, therefore any drugs that have a similar mechanism of excretion may increase the concentration of acyclovir in the blood plasma.
When using the drug simultaneously with other drugs, it is possible:
with probenecid, cimetidine – prolongation of the half-life of acyclovir and the area under the “concentration/time” curve;
with immunosuppressants in patients after organ transplantation - increased levels of acyclovir and the inactive metabolite of the immunosuppressive drug (mycophenolate mofetil) in blood plasma; given the wide therapeutic index of acyclovir, dose adjustment is not required.
An experimental study in 5 men indicated that concomitant acyclovir therapy increased the AUC of fully administered theophylline by approximately 50%. It is recommended that plasma concentrations be measured during concomitant acyclovir therapy.
No clinically significant interactions of acyclovir with other drugs have been identified.
Application features
When using high doses of the drug, an adequate level of hydration of the body should be maintained.
Acyclovir-DARNYTSYA should be used with caution in patients with impaired renal function, since acyclovir is excreted from the body mainly by renal clearance. Dose adjustment should be made (see section "Method of administration and dosage").
Acyclovir-DARNYTSYA should be used with caution in elderly patients, as this group of patients is more likely to have impaired renal function. If necessary, dose adjustment should be made (see section "Method of administration and dosage").
Both these groups (patients with renal impairment and elderly patients) are at risk for neurological disorders and should therefore be closely monitored for these adverse reactions. According to the available data, these reactions are generally reversible upon discontinuation of treatment (see section 4.8).
The risk of kidney damage increases with concomitant use with other nephrotoxic drugs.
Prolonged or repeated courses of acyclovir treatment in severely immunocompromised individuals may result in the isolation of viral strains with reduced susceptibility that may not respond to prolonged acyclovir treatment.
Available clinical trial data are insufficient to conclude that acyclovir treatment reduces the incidence of complications associated with varicella in immunocompetent patients.
Use during pregnancy or breastfeeding
The post-marketing surveillance registry documented the results of the use of various pharmaceutical forms of acyclovir in pregnant women. No increase in the number of birth defects was found in children whose mothers used acyclovir during pregnancy, compared with the general population.
When acyclovir is administered orally at a dose of 200 mg 5 times a day, it penetrates into breast milk in concentrations that are 0.6-4.1% of the corresponding plasma acyclovir level. The child can potentially absorb acyclovir at a dose of up to 0.3 mg/kg body weight per day.
During pregnancy or breastfeeding, the drug should be used only if its potential benefit to the mother outweighs the possible risk to the fetus.
There is no information on the effect of acyclovir on female fertility.
In a study of 20 male patients with normal sperm counts, oral administration of up to 1 g per day for 6 months showed no clinically significant effects on sperm count, motility, or morphology.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical studies of the effect of acyclovir on the speed of reaction when driving or working with other mechanisms have not been conducted. The pharmacology of acyclovir does not give reason to expect any negative effect. When deciding whether to drive or use other mechanisms, the clinical status of the patient and the adverse reaction profile of the drug should be taken into account.
Method of administration and doses
The tablet should be taken whole with water. When using high doses of the drug, an adequate level of hydration of the body should be maintained.
Adults.
Treatment of infections caused by the Herpes simplex virus.
ACICLOVIR-DARNYTSYA should be administered at a dose of 200 mg 5 times a day with approximately 4-hour intervals, except at night. The duration of treatment is 5 days, but in case of severe primary infection it may be extended.
If necessary, in patients with severe immunodeficiency (e.g. after bone marrow transplantation) or with reduced intestinal absorption, the single dose can be doubled to 400 mg or an appropriate dose for intravenous administration can be used.
Treatment should be started as early as possible after the onset of infection. In the case of recurrent herpes, it is best to start treatment in the prodromal period or after the first signs of skin lesions appear.
Prevention of recurrence of infections caused by the Herpes simplex virus in patients with normal immunity.
ACICLOVIR-DARNYTSYA should be used at a dose of 200 mg 4 times a day with a 6-hour interval (or for convenience – at a dose of 400 mg 2 times a day with a 12-hour interval).
Treatment will be effective even after reducing the dose of the drug to 200 mg 3 times a day with an 8-hour interval or even 2 times a day with an 12-hour interval.
In some cases, radical improvement is observed after taking a daily dose of 800 mg of the drug.
To monitor possible changes in the natural course of the disease, drug therapy should be interrupted periodically at intervals of 6-12 months.
Prevention of infections caused by the Herpes simplex virus in immunocompromised patients.
ACICLOVIR-DARNYTSYA should be used at a dose of 200 mg 4 times a day with a 6-hour interval.
If necessary, in patients with severe immunodeficiency or with reduced intestinal absorption, the single dose can be doubled to 400 mg or an appropriate dose for intravenous administration can be used.
The duration of prophylaxis depends on the duration of the risk period.
ACICLOVIR-DARNYTSYA should be administered at a dose of 800 mg 5 times a day with approximately 4-hour intervals, except at night. Duration of treatment – 7 days.
Treatment should be started as early as possible after the onset of the disease; the result will be better if therapy is started immediately after the appearance of the rash.
Patients with severe immunodeficiency (e.g., after bone marrow transplantation) or with reduced intestinal absorption are better served by intravenous administration of the drug.
Children aged 2 years and over.
Treatment and prevention of infections caused by the Herpes simplex virus in immunocompromised children.
ACICLOVIR-DARNYTSYA should be used in doses as for adults.
Treatment of chickenpox.
ACICLOVIR-DARNYTSYA should be used in the following doses: children aged 2 to 6 years – 400 mg 4 times a day, children aged 6 years and over – 800 mg 4 times a day.
More precisely, the dose of the drug can be calculated based on the child's body weight - 20 mg/kg of body weight per day, divided into 4 doses. The maximum daily dose is 800 mg. The duration of treatment is 5 days.
There are no specific data on the use of acyclovir for the prevention of infections caused by the herpes simplex virus or for the treatment of infections caused by the herpes zoster virus in children with normal immunity.
Patients with renal impairment.
Acyclovir-DARNYTSYA should be used with caution. It is necessary to maintain an adequate level of hydration of the body.
In the prevention and treatment of infections caused by the Herpes simplex virus, in patients with renal insufficiency, the recommended oral doses do not lead to accumulation of acyclovir, the level of which would exceed the safe level established for intravenous administration. However, in patients with severe renal insufficiency (creatinine clearance less than 10 ml/min), it is recommended to use Acyclovir-DARNYTSYA at a dose of 200 mg 2 times a day with an interval of approximately 12 hours.
When treating infections caused by the Varicella zoster virus, patients with significantly reduced immunity are recommended to use ACICLOVIR-DARNYTSYA at a dose of: in severe renal failure (creatinine clearance less than 10 ml/min) - 800 mg 2 times a day with an interval of approximately 12 hours, in moderate renal failure (creatinine clearance within 10–25 ml/min) - 800 mg 3 times a day with an interval of approximately 8 hours.
Elderly patients.
Acyclovir-DARNYTSYA should be used with caution. It is necessary to maintain an adequate level of hydration of the body.
The possibility of impaired renal function in elderly patients should be borne in mind, and the dose of the drug for them should be adjusted accordingly.
Children
ACICLOVIR-DARNYTSYA should be used in children over 2 years of age.
Overdose
Symptoms: Acyclovir is only partially absorbed from the gastrointestinal tract. Accidental ingestion of up to 20 g of acyclovir has been reported without toxic effects.
In case of accidental overdose of oral acyclovir, the following symptoms occur within several days: gastroenterological (nausea, vomiting) and neurological (headache, confusion).
Overdose of intravenous acyclovir increases serum creatinine levels and, accordingly, renal failure occurs. Neurological manifestations of overdose may include confusion, hallucinations, agitation, seizures, and coma.
Treatment: should be examined for symptoms of intoxication, symptomatic therapy should be carried out, in severe cases - hemodialysis.
Side effects
The adverse reactions listed below are classified by system organ class and frequency of occurrence. Frequency categories: very common ≥ 1/10, common ≥ 1/100 and < 1/10, uncommon ≥ 1/1000 and < 1/100, rare ≥ 1/10000 and < 1/1000, very rare < 1/10000.
Respiratory, thoracic and mediastinal disorders: rarely - shortness of breath.
Gastrointestinal: rarely - nausea, vomiting, diarrhea, abdominal pain, decreased appetite, gastritis, dysphagia.
From the liver and biliary tract: rarely - transient increase in liver enzyme activity and bilirubin level; very rarely - jaundice, hepatitis.
On the part of the kidneys and urinary system: rarely - increased concentration of urea and creatinine in the blood; very rarely - acute renal failure, pain in the kidney area.
Pain in the kidney area may be associated with renal failure and crystalluria.
From the nervous system: often - headache, dizziness; very rarely - psychomotor agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.
The above symptoms are in most cases reversible and are observed mainly in patients with renal insufficiency or other predisposing factors (see section "Special warnings and precautions for use").
From the cardiovascular system: rarely - palpitations, chest pain.
From the blood and lymphatic system: very rarely - anemia, leukopenia, thrombocytopenia.
Immune system disorders: rarely - hypersensitivity reactions, including angioedema, anaphylactic reactions.
Skin and subcutaneous tissue disorders: common: rash, itching, photosensitivity; uncommon: hyperemia, urticaria, alopecia.
General disorders and administration site conditions: common: fatigue, fever.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a contour blister pack; 2 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
