Instructions for Lipster tablets 800mg No. 20
Composition
active ingredient: acyclovir;
1 tablet contains acyclovir calculated as 100% anhydrous substance 200 mg or 400 mg, or 800 mg;
Excipients: microcrystalline cellulose, povidone, sodium starch glycolate (type A), magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
200 mg tablets: round tablets with a biconvex surface, white or almost white in color;
400 mg tablets: round tablets with a biconvex surface, white or almost white in color;
800 mg tablets: oblong tablets with a biconvex surface, with a score on one side, white or almost white in color.
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 order of decreasing 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 viruses, herpes zoster viruses and Epstein-Barr viruses, 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. About 20% of the dose is absorbed soon after administration. When doses of 600 mg or more are taken, acyclovir is absorbed relatively little. The average peak steady-state concentration (Cssmax) in plasma 4 hours after a 200 mg dose is 3 μmol/l, and the lowest concentration Cssmin is 1.6 μmol/l. After a dose of 800 mg, the corresponding concentrations were 6.9 μmol/l and 3.5 μmol/l. Most of the drug is excreted unchanged by the kidneys.
When acyclovir was administered to a group of newborns at a dose of 15 mg/kg every 8 hours, the following values were observed: Cmax - 83.5 μmol (18.8 μg/ml), Cmin - 14.1 μmol (3.2 μg/ml).
Renal clearance of acyclovir is significantly higher than creatinine clearance, indicating that the drug is eliminated not only by glomerular filtration but also by tubular secretion. The plasma half-life of acyclovir is about 3 hours under normal renal function. The only major metabolite of acyclovir that can be detected in urine is 9-carboxymethoxymethylguanine, which accounts for 10 to 15% of the administered dose.
In chronic renal failure, the terminal half-life of the drug increases to 19.5 hours. The average concentration of acyclovir during dialysis decreases by approximately 60%.
In the elderly, clearance decreases with age as creatinine clearance decreases, but the terminal half-life is almost unchanged. When acyclovir and zidovudine were co-administered in HIV patients, no changes in the pharmacokinetics of either drug were detected.
In a mutagenicity study, an effect was detected in 2 of 11 mammalian cell tests at concentrations that were 25 times (after intravenous administration) and 150 times (after oral administration) higher than the drug level in human plasma.
Indication
- Infections of the skin and mucous membranes caused by the Herpes simplex virus, including primary genital herpes infections and relapses (except neonatal herpes simplex infections and severe infections caused by Herpes simplex in children with impaired immune response).
- For the prevention of recurrent Herpes simplex infections in patients with normal immunity.
- For the prevention of Herpes simplex infection in immunocompromised patients.
- For the treatment of infections caused by the Varicella zoster virus (chickenpox and 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 with a similar mechanism of excretion may increase the plasma concentration of acyclovir.
Probenecid and cimetidine prolong the half-life of acyclovir and increase the AUC of acyclovir.
Concomitant administration of acyclovir with mycophenolate mofetil, an immunosuppressant used in transplant patients, has been shown to increase the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil. However, given the wide therapeutic index of acyclovir, no dose adjustment is necessary.
In an experimental study of the simultaneous use of acyclovir and theophylline in 5 people, an increase in the AUC of the total dose of theophylline by approximately 50% was found. It is recommended to monitor the plasma theophylline content during concomitant treatment with acyclovir.
Application features
Hydration: Patients receiving large doses of acyclovir orally or parenterally should be ensured to receive adequate fluids.
The use of other nephrotoxic drugs increases the risk of renal failure.
Use in patients with renal insufficiency and elderly patients: Acyclovir is excreted by the kidneys, and therefore the dose should be reduced in patients with renal insufficiency. It should be borne in mind that the elderly are more likely to have impaired renal function, so a dose reduction may also be necessary for this category. Elderly patients and patients with renal insufficiency are at increased risk of developing neurological adverse reactions, so careful monitoring for the occurrence of these adverse reactions is necessary. In the reported cases, these reactions were usually reversible upon discontinuation of treatment.
In patients with severe immunodeficiency, prolonged treatment with acyclovir or periodic repeated courses of treatment with acyclovir may lead to the emergence of viral strains with reduced sensitivity to acyclovir. In such cases, continued treatment with acyclovir may be ineffective.
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
Pregnancy
Acyclovir should be used only when the potential benefit of the drug to the pregnant woman outweighs the possible risk to the fetus.
The post-marketing surveillance registry has documented the results of the use of various pharmaceutical forms of acyclovir in pregnant women. No increase in the number of congenital malformations was found in children whose mothers used acyclovir during pregnancy. In standard tests, systemic acyclovir did not cause any embryotoxic or teratogenic effects in rabbits, rats, or mice. In a non-standardized test in rats, fetal anomalies were found, but only after the administration of large subcutaneous doses that were toxic to the mother. The clinical significance of these findings is unknown.
Feeding
After oral administration of 200 mg 5 times daily, acyclovir is found in breast milk at concentrations that are 0.6 to 4.1 times the plasma acyclovir level. The potential dose to the breastfed infant is up to 0.3 mg/kg/day. Therefore, acyclovir should be administered with caution to nursing mothers, taking into account the risk/benefit ratio.
Fertility
The effect of oral or parenteral acyclovir on female fertility is unknown. In a study of oral acyclovir at a dose of 1 gram per day for 6 months in men, there was no clinically significant effect of acyclovir on sperm count, motility, or morphology.
Ability to influence reaction speed when driving vehicles or other mechanisms
When considering the possibility of driving a car and other mechanisms, the clinical status of the patient and the side effect profile of the drug should be taken into account. Clinical studies of the effect of acyclovir on the speed of reaction when driving a car or working with other mechanisms have not been conducted. In addition, the pharmacology of acyclovir does not give reason to expect any negative effects.
Method of administration and doses
The tablet should be taken whole with water.
| Purpose of application | Dosage |
| Adults |
| Treatment of Herpes simplex infection | 1 tablet at a dose of 200 mg 5 times a day for 5 days |
| Prevention of Herpes simplex infection | 1 tablet at a dose of 400 mg 2 times a day |
| Treatment of Varicella zoster infection | 1 tablet at a dose of 800 mg 5 times a day for 7 days |
| Children aged 2 years and over |
| Treatment of Herpes simplex infection | 1 tablet at a dose of 200 mg 5 times a day for 5 days |
Treatment of Herpes simplex infection
Pediatric patients: In the treatment of Herpes simplex infection in children aged 2 years and older, the adult dose can be used.
Elderly patients: When treating elderly patients, the possible presence of renal insufficiency should be taken into account and the need for dose adjustment should be assessed accordingly. Patients receiving large oral doses of acyclovir should be adequately hydrated.
Renal impairment: Acyclovir should be used with caution in patients with renal impairment. Adequate hydration should be ensured. In the treatment of Herpes simplex infection in patients with severe renal impairment (glomerular filtration rate < 10 ml/min), it is recommended to reduce the dose to 200 mg 2 times a day every 12 hours.
Prevention of Herpes simplex infection in patients with a normal immune response
Prophylaxis should be performed in patients with laboratory-confirmed frequent recurrences of Herpes simplex.
Adults: 1 tablet of 200 mg 4 times a day every 6 hours. A possible scheme of use of tablets of 400 mg 2 times a day with an interval of 12 hours. Also, treatment can be effective when reducing the daily dose to 600 mg: 200 mg 3 times a day every 8 hours or even 200 mg 2 times a day every 12 hours. In some patients, stopping the infection is possible when taking 800 mg per day.
Elderly patients: When treating elderly patients, the possible presence of renal insufficiency should be taken into account and the need for dose adjustment should be assessed accordingly. Patients receiving large oral doses of acyclovir should be adequately hydrated.
Renal impairment: Acyclovir should be used with caution in patients with renal impairment. Adequate hydration should be ensured.
Prevention of Herpes simplex infection in patients with a weakened immune response
Adults: 1 tablet of 200 mg 4 times a day every 6 hours. For patients with severe immunodeficiency (e.g. after bone marrow transplantation) or for patients with reduced absorption of the drug from the intestine, a dose of 400 mg 4 times a day may be used or, alternatively, the appropriate dose of acyclovir in a dosage form for intravenous administration. The duration of prophylactic use of acyclovir is determined depending on the duration of the risk period.
Pediatric patients: For the prevention of infections caused by the Herpes simplex virus, the adult dose can be used in immunocompromised children aged 2 years and older.
There are no adequate data on the use of acyclovir for the prophylaxis (prevention of recurrence) 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.
Elderly patients: When treating elderly patients, the possible presence of renal insufficiency should be taken into account and the need for dose adjustment should be assessed accordingly. Patients receiving large oral doses of acyclovir should be adequately hydrated.
Renal impairment: Acyclovir should be used with caution in patients with renal impairment. Adequate hydration should be ensured. In the treatment and prevention of Herpes simplex infection in patients with severe renal impairment (glomerular filtration rate < 10 ml/min), it is recommended to reduce the dose to 200 mg 2 times a day every 12 hours. In such patients, the half-life of acyclovir is about 20 hours, so with longer dosing intervals, the recommended single dose does not result in higher plasma levels.
Treatment of herpes zoster and chickenpox
Adults: 1 tablet of 800 mg 5 times a day every 4 hours, except at night. Duration of treatment - 7 days.
For patients with significant immunosuppression (e.g., after bone marrow transplantation) or with malabsorption, intravenous acyclovir should be considered.
Treatment should be started as soon as possible after the onset of the disease - the best results are achieved if treatment is started as early as possible after the appearance of skin symptoms.
Pediatric patients
For children over 6 years of age: 1 tablet of 800 mg 4 times a day; for children 2–6 years of age: 1 tablet of 400 mg 4 times a day. The treatment period is 5 days. A more accurate single dose of the drug can be calculated based on the child's body weight as 20 mg/kg of body weight (not to exceed 800 mg) of acyclovir 4 times a day.
Elderly patients: When treating elderly patients, the possible presence of renal insufficiency should be taken into account and the need for dose adjustment should be assessed accordingly. Patients receiving large oral doses of acyclovir should be adequately hydrated.
Renal impairment: Acyclovir should be used with caution in patients with renal impairment. Adequate hydration should be ensured. Patients with moderate renal impairment (glomerular filtration rate 10–25 mL/min) are recommended to take 800 mg 3 times a day every 8 hours. Patients with severe renal impairment (glomerular filtration rate < 10 mL/min) are recommended to take 800 mg 2 times a day every 12 hours.
Acyclovir is not suitable for the prevention of chickenpox in healthy people.
Children.
Acyclovir tablets should be used in children aged 2 years and older as indicated in the “Method of administration and dosage” section.
Overdose
Acyclovir is only partially absorbed from the gastrointestinal tract. There are cases of accidental ingestion of up to 20 g of acyclovir by patients without toxic effects. Accidental repeated overdose of oral acyclovir over several days causes gastrointestinal (such as nausea and vomiting) and neurological symptoms (headache and confusion).
Overdose of intravenous acyclovir increases serum creatinine and blood urea nitrogen, leading to renal failure. Neurological manifestations of overdose may include confusion, hallucinations, agitation, convulsions, and coma.
Treatment.
The patient should be carefully examined for signs of intoxication. Since acyclovir is well eliminated from the blood by hemodialysis, the latter should be used in case of overdose.
Adverse reactions
Adverse reactions are classified by frequency as follows: very common ≥ 1/10; common ≥ 1/100, < 1/10; uncommon ≥ 1/1000, < 1/100; rare ≥ 1/10,000, < 1/1000; very rare < 1/10,000.
Blood and lymphatic system disorders
Very rare: anemia, leukopenia, thrombocytopenia.
On the part of the immune system
Rare: anaphylaxis.
Mental and nervous system disorders
Common: headache, dizziness.
Very rare: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.
The above neurological reactions are usually reversible and usually occur in patients with renal insufficiency or other risk factors (see section "Special warnings and precautions for use").
Respiratory, thoracic and mediastinal disorders
Rare: shortness of breath.
From the digestive system
Common: nausea, vomiting, diarrhea, abdominal pain.
Hepatobiliary system
Rare: reversible increases in bilirubin and liver enzymes.
Very rare: hepatitis, jaundice.
Skin and subcutaneous tissue disorders
Common: pruritus, rash (also photosensitivity)
Uncommon: urticaria, accelerated diffuse hair loss.
Accelerated diffuse hair loss is associated with many diseases and medications, but no clear link to acyclovir has been found.
Rare: angioedema.
Renal and urinary disorders
Rare: increased blood urea and creatinine levels.
Very rare: acute renal failure, kidney pain.
Kidney pain may be associated with renal failure and crystalluria.
General disorders and administration site conditions
Common: fatigue, fever.
Expiration date
2 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
The drug does not require special storage conditions.
Keep out of reach of children.
Packaging
10 tablets in a blister. 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address.
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
