Instructions Acyclovir tablets 0.2 g blister No. 20
Composition
active ingredient: aciclovir;
1 tablet contains acyclovir 200 mg (0.2 g);
Excipients: lactose monohydrate, corn starch, magnesium stearate, croscarmellose sodium.
Dosage form
Pills.
Main physicochemical properties: white or almost white tablets.
Pharmacotherapeutic group
Antivirals for systemic use. Direct-acting antivirals. Acyclovir. 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 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 the termination of viral DNA chain synthesis.
With prolonged or repeated courses of treatment of severely immunocompromised patients, cases of reduced sensitivity of individual virus strains may occur, 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 may 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 has not been fully elucidated.
Pharmacokinetics.
Acyclovir is only partially absorbed from the gut. The mean peak steady-state plasma concentration (Cssmax) after a 200 mg dose administered 4 hours apart is 3.1 μmol (0.7 μg/ml) and the corresponding plasma level (Cssmin) is 1.8 μmol (0.4 μg/ml). The corresponding Cssmax levels after 400 mg and 800 mg doses administered 4 hours apart are 5.3 μmol (1.2 μg/ml) and 8 μmol (1.8 μg/ml) and the equivalent Cssmin levels are 2.7 μmol (0.6 μg/ml) and 4 μmol (0.9 μg/ml).
In adults, the terminal half-life of intravenous acyclovir is approximately 2.9 hours. The majority of the drug is excreted unchanged by the kidneys. Renal clearance of acyclovir is significantly higher than creatinine clearance, indicating that renal elimination of the drug is by tubular secretion as well as glomerular filtration.
9-Carboxymethoxymethylguanine is the only major metabolite of acyclovir and accounts for approximately 10-15% of the administered dose that can be detected in the urine. When acyclovir is administered 1 hour after 1 g of probenecid, the terminal half-life and area under the concentration-time curve increase by 18% and 40%, respectively.
In patients with chronic renal failure, the mean terminal half-life is 19.5 hours. The mean half-life of acyclovir during hemodialysis is 5.7 hours. The plasma level of acyclovir is reduced by approximately 60% during dialysis.
The concentration of the drug in the cerebrospinal fluid is approximately 50% of the corresponding concentration in the blood plasma. The level of binding to plasma proteins is relatively low (from 9% to 33%), and it does not change when interacting with other drugs.
When acyclovir and zidovudine were used simultaneously for the treatment of HIV-infected patients, no changes in the pharmacokinetics of these drugs were detected.
Clinical characteristics.
Indication
- Treatment of viral infections of the skin and mucous membranes caused by the herpes simplex virus, including primary and recurrent genital herpes;
- suppression (prevention of relapses) 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 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, so any drugs that have a similar mechanism of excretion can increase the concentration of acyclovir in the blood plasma. Probenecid and cimetidine prolong the half-life of acyclovir and the area under the "concentration/time" curve. When used simultaneously with immunosuppressants in the treatment of patients after organ transplantation, the level of acyclovir and the inactive metabolite of the immunosuppressive drug in the blood plasma also increases, but due to the wide therapeutic index of acyclovir, dose adjustment is not required.
Application features
Acyclovir is eliminated primarily by renal clearance, and therefore the dose should be reduced in patients with renal impairment (see Dosage and Administration). Elderly patients are also more likely to have impaired renal function, and a dose reduction may be necessary in this patient group. Both groups (renal impairment and elderly patients) are at risk for neurological adverse events and should be monitored closely for these adverse events. These events have been reported to be generally reversible upon discontinuation of treatment.
Special attention should be paid to maintaining adequate hydration in patients receiving high doses of acyclovir.
The drug contains lactose, so it should not be used in patients with hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Use during pregnancy or breastfeeding
There has been no increase in the number of birth defects in children whose mothers used acyclovir during pregnancy compared with the general population. However, acyclovir tablets should be used only when the potential benefit to the mother outweighs the potential risk to the fetus.
When 200 mg of acyclovir is taken orally 5 times a day, acyclovir penetrates into breast milk in concentrations of 0.6-4.1% of the corresponding plasma acyclovir level. Potentially, a breastfed child can absorb acyclovir at a dose of up to 0.3 mg/kg body weight per day. Therefore, acyclovir should be prescribed to breastfeeding women with caution, taking into account the risk/benefit ratio.
Ability to influence reaction speed when driving vehicles or other mechanisms
When deciding whether to drive or operate machinery, the patient's clinical status 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 or operating other mechanisms have not been conducted. In addition, the pharmacology of acyclovir does not give reason to expect any negative effect.
Method of administration and doses
The tablet should be taken whole with water. When using high doses of acyclovir, adequate hydration should be maintained.
Adults
Treatment of infections caused by the herpes simplex virus.
To treat infections caused by the herpes simplex virus, it is necessary to take acyclovir tablets at a dose of 200 mg 5 times a day at approximately 4-hour intervals, except at night.
Treatment should last 5 days, but in case of severe primary infection it may be extended.
For some immunocompromised patients (e.g. after bone marrow transplantation) or for patients with reduced intestinal absorption, the dose may be doubled to 400 mg or an appropriate intravenous dose may 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 (suppressive therapy) of infections caused by the herpes simplex virus.
In patients with normal immunity, to prevent recurrence of infections caused by the herpes simplex virus, acyclovir tablets at a dose of 200 mg should be taken 4 times a day with
6-hour interval.
For convenience, most patients can take 400 mg of acyclovir twice daily with
12-hour interval.
Treatment will be effective even after reducing the dose of tableted acyclovir to 200 mg, which should be taken 3 times a day with an 8-hour interval or even 2 times a day with an 12-hour interval.
Some patients experience radical improvement after taking a daily dose of 800 mg of acyclovir.
To monitor possible changes in the natural course of the disease, acyclovir therapy should be interrupted periodically at intervals of 6-12 months.
Prevention of infections caused by the herpes simplex virus.
To prevent infections caused by the herpes simplex virus, in immunocompromised patients, acyclovir tablets at a dose of 200 mg should be taken 4 times a day with
6-hour interval. In patients with significant immunodeficiency (e.g. after bone marrow transplantation) or in patients with reduced intestinal absorption, the dose can be doubled to 400 mg or an appropriate dose for intravenous administration can be used.
The duration of prophylactic use is determined by the duration of the risk period.
For the treatment of infections caused by the varicella and herpes zoster viruses, acyclovir tablets should be taken at a dose of 800 mg 5 times a day at 4-hour intervals, excluding the night period. Treatment should last 7 days.
In patients with severe immunodeficiency (e.g., after bone marrow transplantation) or in patients with reduced intestinal absorption, intravenous administration is preferable.
Treatment should be started as early as possible after the onset of the disease, the result will be better if treatment is started immediately after the appearance of the rash.
Children.
For the treatment and prevention of infections caused by the herpes simplex virus, the same doses as for adults can be used in immunocompromised children aged 2 years and older.
For the treatment of chickenpox, children aged 6 years and older should be prescribed 800 mg of acyclovir 4 times a day, and children aged 2 to 6 years should be given 400 mg of acyclovir 4 times a day. The duration of treatment is 5 days.
The dose of the drug can be calculated more accurately based on the child's body weight - 20 mg/kg of body weight per day (not to exceed 800 mg) of acyclovir, divided into 4 doses.
There are no specific 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.
This dosage form of the drug should not be used in children under 2 years of age.
Elderly patients.
The possibility of impaired renal function in elderly patients should be borne in mind and the dose of the drug should be adjusted accordingly (see Renal failure). Adequate hydration should be maintained.
Kidney failure.
Acyclovir should be administered with caution to patients with renal insufficiency. Adequate hydration should be maintained.
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 establish 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 (chickenpox and herpes zoster), in patients with significantly reduced immunity, it is recommended that in severe renal failure (creatinine clearance less than 10 ml/min) a dose of 800 mg be established 2 times a day with an interval of approximately 12 hours, and in patients with moderate renal failure (creatinine clearance within 10-25 ml/min) - 800 mg 3 times a day with an interval of approximately 8 hours.
Children
Acyclovir tablets should be used in children over 2 years of age.
Overdose
Symptoms.
Acyclovir is only partially absorbed from the gastrointestinal tract. There have been 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 has resulted in gastroenterological (such as nausea and vomiting) and neurological symptoms (headache and confusion).
Overdose of intravenous acyclovir increases serum creatinine and blood urea nitrogen levels, and renal failure occurs. Neurological manifestations of overdose may include confusion, hallucinations, agitation, convulsions, and coma.
Treatment: the patient should be carefully examined for symptoms of intoxication. Gastric lavage and symptomatic treatment are recommended. Since acyclovir levels in the blood are well eliminated by hemodialysis, it should be used in case of overdose.
Adverse reactions
The side effects listed below are classified as follows.
From the blood and lymphatic system.
Anemia, thrombocytopenia, leukopenia.
From the immune system.
Anaphylaxis.
Mental and nervous system disorders.
Headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.
The above neurological reactions are generally reversible and usually occur when used to treat patients with renal insufficiency or other risk factors.
On the part of the respiratory system and chest organs.
Dyspnea.
From the gastroenterological system.
Nausea, vomiting, diarrhea, abdominal pain.
On the part of the hepatobiliary system.
Reversible increase in bilirubin and liver enzymes, jaundice, hepatitis.
On the skin and subcutaneous tissue.
Pruritus, rash (including photosensitivity), urticaria, accelerated diffuse hair loss. Since hair loss can be associated with a large number of diseases and medications used by the patient, no clear relationship with acyclovir has been found. Angioedema.
On the part of the kidneys and urinary system.
Increased blood urea and creatinine levels, acute renal failure, kidney pain.
Kidney pain may be associated with renal failure and crystalluria.
General disorders.
Increased 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 blister; 1 or 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
Private Joint-Stock Company "Lekhim-Kharkiv".
Technolog PJSC.
Location of the manufacturer and address of its place of business
Ukraine, 61115, Kharkiv region, Kharkiv city, Severyna Pototskoho street, building 36.
Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna Street, building 8.
