Aciclovir, tablets 200 mg 20 pcs

Pharmacotherapeutic group: antiviral agent.

Code ATX: J05AB01.

Pharmacological properties:

Pharmacodynamics

Mechanism of Action

. Acyclovir is a synthetic analog of the purine nucleoside that has the ability to inhibit invitroinvivo human herpes viruses, including herpes simplex virus (HPV) types 1 and 2, varicella zoster virus (Varicella zoster virus (VZV)), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture acyclovir has the most pronounced antiviral activity against HPV-1, followed in descending order of activity by HPV-2, VZV, EBV and CMV.

In patients with severe immunodeficiency, prolonged or repeated courses of acyclovir therapy may lead to the emergence of resistant strains, so further treatment with acyclovir may not be effective. Most isolated strains with reduced sensitivity to acyclovir had relatively low thymidine kinase content, as well as disruption of viral thymidine kinase or DNA polymerase structure. Exposure to acyclovir on herpes simplex virus (HPV) strains invitro can also produce less sensitive strains. No correlation has been established between the sensitivity of herpes simplex virus (HPV) strains to acyclovir invitro and the clinical efficacy of the drug.

Pharmacokinetics

.Absorption

Acyclovir is only partially absorbed from the intestine. After administration of 200 mg of acyclovir every 4 hours, the mean maximum equilibrium plasma concentration (Cs_max) was 3.1 µM (0.7 µg/mL) and the mean equilibrium minimum plasma concentration (Cs_min) was 1.8 µM (0.4 µg/mL). When administered orally, 400 mg and 800 mg of acyclovir every 4 hours, the Cs_max was 5.3 µM (1.2 µg/mL) and 8 µM (1.8 µg/mL), respectively, and Cs_min was 2.7 µM (0.6 µg/mL) and 4 µM (0.9 µg/mL), respectively.

Distribution

The concentration of acyclovir in cerebrospinal fluid is approximately 50% of its concentration in plasma.

Aciclovir binds only slightly (9-33%) with blood plasma proteins, therefore drug interactions due to displacement from binding sites with blood plasma proteins are unlikely.

Elimation

In adults after oral administration of acyclovir the elimination half-life from the blood plasma is about 3 hours. Most of the drug is excreted unchanged by the kidneys. Renal clearance of acyclovir significantly exceeds creatinine clearance, which indicates excretion of acyclovir by not only glomerular filtration but also by tubular secretion. 9-carboxymethoxy-methylguanine is the main metabolite of acyclovir and accounts for about 10-15% of the dose excreted in the urine. When acyclovir was administered 1 h after 1 g of probenecid, the acyclovir elimination half-life and AUC (area under the pharmacokinetic “concentration-time” curve) increased by 18 and 40%, respectively.

Special patient groups

In patients with chronic renal failure the half-life of acyclovir averaged 19.5 h. During hemodialysis the average half-life of acyclovir was 5.7 h. The plasma concentration of acyclovir during dialysis decreased by approximately 60%.

In elderly patients, the overall clearance of acyclovir decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir does not change significantly.

The pharmacokinetic characteristics of both drugs were virtually unchanged when acyclovir and zidovudine were administered simultaneously to HIV-infected patients.

Indications

– Treatment of infections of the skin and mucous membranes caused by the herpes simplex virus, including primary and recurrent genital herpes;

– prevention of relapses of infections caused by the herpes simplex virus in patients with normal immune status;

– prevention of infections caused by the herpes simplex virus in patients with immunodeficiency;

– treatment of chickenpox and herpes zoster (early treatment of herpes zoster with acyclovir has an analgesic effect and can reduce the incidence of postherpetic neuralgia).

Pharmacological effect

Pharmacotherapeutic group: antiviral agent.

ATX code: J05AB01.

Pharmacological properties:

Pharmacodynamics

Mechanism of action

Acyclovir is a synthetic analogue of a purine nucleoside that has the ability to inhibit in vitro and in vivo human herpes viruses, including herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the most pronounced antiviral activity against HSV-1, followed in descending order of activity by HSV-2, VZV, EBV and CMV.

The inhibitory effect of acyclovir on herpes viruses (HSV-1, HSV-2, VZV, EBV and CMV) is highly selective. Acyclovir is not a substrate for the thymidine kinase enzyme in uninfected cells, therefore acyclovir is of low toxicity to mammalian cells. However, thymidine kinase of cells infected with HSV, VZV, EBV and CMV viruses converts acyclovir into acyclovir monophosphate, a nucleoside analogue, which is then sequentially converted into diphosphate and triphosphate under the action of cellular enzymes. The incorporation of acyclovir triphosphate into the viral DNA chain and subsequent chain termination blocks further replication of the viral DNA.

In patients with severe immunodeficiency, long-term or repeated courses of acyclovir therapy may lead to the emergence of resistant strains, so further treatment with acyclovir may be ineffective. Most isolated strains with reduced sensitivity to acyclovir had a relatively low content of thymidine kinase, as well as a disorder in the structure of the viral thymidine kinase or DNA polymerase. In vitro exposure of herpes simplex virus (HSV) strains to acyclovir may also result in the formation of strains that are less sensitive to it. A correlation has not been established between the sensitivity of herpes simplex virus (HSV) strains to acyclovir in vitro and the clinical effectiveness of the drug.

Pharmacokinetics

Suction

Acyclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the mean maximum steady-state plasma concentration (Cssmax) was 3.1 μM (0.7 μg/ml), and the mean steady-state minimum plasma concentration (Cssmin) was 1.8 μM (0.4 μg/ml). When 400 mg and 800 mg of acyclovir were taken orally every 4 hours, Cssmax was 5.3 µM (1.2 µg/ml) and 8 µM (1.8 µg/ml), respectively, and Cssmin was 2.7 µM (0.6 µg/ml) and 4 µM (0.9 µg/ml), respectively.

Distribution

The concentration of acyclovir in cerebrospinal fluid is approximately 50% of its concentration in blood plasma.

Acyclovir binds to blood plasma proteins to an insignificant extent (9-33%), so drug interactions due to displacement from binding sites with blood plasma proteins are unlikely.

Removal

In adults, after taking acyclovir orally, the half-life from blood plasma is about 3 hours. Most of the drug is excreted unchanged by the kidneys. The renal clearance of acyclovir significantly exceeds the clearance of creatinine, which indicates that acyclovir is eliminated through not only glomerular filtration, but also tubular secretion. 9-carboxymethoxy-methylguanine is the main metabolite of acyclovir and accounts for about 10-15% of the dose excreted in the urine. When acyclovir was administered 1 hour after taking 1 g of probenecid, the half-life of acyclovir and AUC (area under the concentration-time pharmacokinetic curve) increased by 18 and 40%, respectively.

Special patient groups

In patients with chronic renal failure, the half-life of acyclovir averaged 19.5 hours. During hemodialysis, the average half-life of acyclovir was 5.7 hours. The plasma concentration of acyclovir decreased by approximately 60% during dialysis.

In elderly patients, the total clearance of acyclovir decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir changes slightly.

When acyclovir and zidovudine were administered simultaneously to HIV-infected patients, the pharmacokinetic characteristics of both drugs remained virtually unchanged.

Special instructions

The available data from clinical trials are insufficient to conclude that the use of acyclovir reduces the risk of varicella in patients with normal immune status.

The risk of developing renal failure increases when used simultaneously with other nephrotoxic drugs.

Hydration status

Patients taking high doses of Acyclovir by mouth should receive sufficient fluids.

Elderly patients and patients with impaired renal function

Since acyclovir is excreted by the kidneys, doses should be reduced in patients with renal failure (see section “Dosage and Administration”).

Elderly patients may experience decreased renal function; therefore, a dose reduction may also be required for this group of patients. Both elderly patients and patients with impaired renal function are at increased risk of developing side effects from the nervous system (such reactions are usually reversible in response to drug withdrawal) and, accordingly, should be under close medical supervision.

Patients with severe immunodeficiency

Long-term or repeated courses of treatment with acyclovir in patients with severe immunodeficiency may lead to the emergence of strains of the virus with reduced sensitivity to acyclovir that will not respond to continued therapy with acyclovir.

Transmission of infection

All patients, especially those who are symptomatic, should exercise caution to avoid potential transmission of the virus. Patients should be informed about cases of asymptomatic virus carriage.

Impact on the ability to drive vehicles and machinery:

There have been no studies of the effect of acyclovir on the ability to drive vehicles or operate machinery. It is not possible to predict the negative impact of acyclovir on these activities based on the pharmacological properties of the active substance, but it is necessary to take into account the side effect profile of acyclovir.

Active ingredient

Acyclovir

Composition

For one tablet:

Active ingredient:

Acyclovir – 200.0 mg.

Excipients:

lactose monohydrate – 137.0 mg, potato starch – 45.0 mg, sucrose – 16.0 mg, povidone K-17 – 7.6 mg, magnesium stearate – 3.0 mg, sodium lauryl sulfate – 1.4 mg.

Pregnancy

Fertility

There is no data on the effect of acyclovir on female fertility.

A study of 20 male patients with normal sperm counts found that oral acyclovir up to 1 g per day for 6 months had no clinically significant effect on sperm count, motility or morphology.

Pregnancy

The post-registration registry of pregnancies during treatment with acyclovir collected data on pregnancy outcomes in women taking acyclovir in different dosage forms. In an analysis of registry data, there was no increase in the number of birth defects in infants whose mothers took acyclovir during pregnancy compared with the general population. The identified birth defects were not uniform or consistent, suggesting a common cause.

However, caution should be exercised when prescribing Acyclovir to women during pregnancy and assess the expected benefit to the mother and the possible risk to the fetus.

Breastfeeding period

After taking the drug Acyclovir orally at a dose of 200 mg 5 times a day, acyclovir was determined in breast milk at a concentration ranging from 60 to 410% of the plasma concentration. At such concentrations in breast milk, breastfed infants can receive acyclovir in doses up to 0.3 mg/kg/day. Given this, caution should be exercised when prescribing Acyclovir to nursing women.

Contraindications

Hypersensitivity to acyclovir or valacyclovir or any other component of the drug; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; children under 3 years of age.

With caution: Pregnancy, breastfeeding, old age, renal failure, dehydration, simultaneous use with other nephrotoxic drugs.

Side Effects

The frequency categories of adverse reactions listed below are estimates. For most adverse reactions, the necessary data to determine the frequency of occurrence are not available. In addition, the incidence of adverse reactions may vary depending on the indication.

The adverse reactions presented below are listed according to their frequency of occurrence, defined as follows: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (>1/10,000 and <1/1000), very rare (<1/10,000).

Frequency of occurrence of adverse reactions

Blood and lymphatic system disorders

Very rare: anemia, leukopenia, thrombocytopenia.

Immune system disorders

Rarely: anaphylaxis.

Nervous system and mental status disorders

Common: headache, dizziness.

Very rare: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.

Typically, these side effects were observed in patients with renal failure or in the presence of other precipitating factors and were mainly reversible (see section “Special instructions”).

Respiratory, thoracic and mediastinal disorders

Rarely: shortness of breath.

Gastrointestinal disorders

Common: nausea, vomiting, diarrhea, abdominal pain.

Disorders of the liver and biliary tract

Rare: reversible increase in the concentration of bilirubin and liver enzymes in the blood.

Very rare: hepatitis, jaundice.

Skin and subcutaneous tissue disorders

Common: itching, rash, including photosensitivity.

Uncommon: urticaria, rapid diffuse hair loss.

Since rapid diffuse hair loss is observed in various diseases and during therapy with many drugs, its connection with the use of acyclovir has not been established.

Rarely: angioedema.

Very rare: toxic epidermal necrolysis, exudative erythema multiforme.

Renal and urinary tract disorders

Rarely: increased concentrations of urea and creatinine in the blood serum.

Very rare: acute renal failure, renal colic.

Renal colic may be associated with renal failure and crystalluria.

General and administration site disorders

Common: fatigue, fever.

Interaction

No clinically significant interactions were observed with the use of Acyclovir.

Acyclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar route of elimination may increase plasma concentrations of acyclovir.

Acyclovir increases theophylline AUC by approximately 50% when administered concomitantly, so it is recommended that plasma theophylline concentrations be measured when acyclovir is coadministered.

Probenecid and cimetidine increase the AUC (area under the concentration-time curve) of acyclovir and reduce its renal clearance. There was an increase in plasma AUC for acyclovir and the inactive metabolite mycophenolate mofetil, an immunosuppressant used in transplantation, when both drugs were used simultaneously. However, no dose adjustment is required due to the broad therapeutic index of acyclovir.

Overdose

Acyclovir is only partially absorbed from the gastrointestinal tract.

As a rule, no toxic effects have been reported with a random single dose of acyclovir up to 20 g.

With repeated oral doses over several days of doses exceeding the recommended ones, disturbances from the gastrointestinal tract (nausea, vomiting) and nervous system (headache and confusion) were observed.

Sometimes neurological effects such as seizures and coma may occur.

Patients require careful medical observation to identify possible symptoms of intoxication.

Acyclovir is eliminated from the body by hemodialysis, so hemodialysis can be used to treat overdose.

Storage conditions

In a place protected from moisture and light at a temperature not exceeding 25°C.
Keep out of the reach of children.

Shelf life

3 years. Do not use after expiration date.

Manufacturer

ABVA RUS, Russia