Zovirax - instructions for use, dose, side effects, contraindications

Acyclovir is a synthetic analogue of a purine nucleoside. which has the ability to inhibit in vitro and in vivo human herpes viruses, including herpes simplex virus (TIG) of the 1st and 2nd types, the virus of varicella and herpes zoster (varicella-zoster virus, Varicella zoster virus (VZV)), the Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture acyclovir has the most pronounced antiviral activity in relation to HSV-1, then in order of decreasing activity follows: HSV-2, VZV, EBV and CMV.

Inhibitory action acyclovir for herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV) is highly selective. Acyclovir is not a substrate for the enzyme thymidine kinase of uninfected cells, therefore acyclovir low toxicity for mammalian cells. Thymidine kinase of cells infected with HSV, VDV, EBV and CMV viruses converts acyclovir in acyclovir monophosphate - an analogue of a nucleoside, which is then subsequently converted into a diphosphate and triphosphate under the action of cellular enzymes. Inclusion of acyclovir triphosphate in the chain of viral DNA and subsequent chain termination block further replication of the viral DNA.

In patients with severe immunodeficiency, prolonged or repeated courses of therapy with acyclovir may lead to the emergence of resistant strains, so further treatment with acyclovir may not be effective. In most isolated strains with reduced sensitivity to acyclovir, a relatively low content of viral thymidine kinase was observed, a disruption in the structure of viral thymidine kinase or DNA polymerase. The effect of acyclovir on strains of the herpes simplex virus (HSV) in vitro can also lead to the formation of less sensitive strains. Not a correlation was established between the sensitivity of strains of the herpes simplex virus (HSV) to acyclovir in vitro and clinical efficacy of the drug.

Pharmacokinetics:

Suction

Acyclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the average maximum equilibrium concentration in the plasma (C_ssmax) was 3.1 μM (0.7 μg / ml), and the mean equilibrium minimum plasma concentration (C_ssmin) was 1.8 μM (0.4 μg / ml). When taking 400 mg and 800 mg of acyclovir every 4 hours Css_max was 5.3 μM (1.2 μg / ml) and 8 μM (1.8 μg / ml), respectively, a C_ssmin 2.7 μM (0.6 μg / ml) and 4 μM (0.9 μg / ml), respectively.

Distributedande

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

With blood plasma proteins acyclovir binds to an insignificant degree (9-33 %), therefore, drug interactions due to displacement from the binding sites with plasma proteins are unlikely.

Excretion

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

Special patient groups

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

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

With simultaneous administration of acyclovir and zidovudine to HIV-infected patients, pharmacokinetic characteristics of both drugs practically did not change.

Indications:

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

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

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

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

Contraindications:

Zovirax is contraindicated in case of hypersensitivity to acyclovir or valaciclovir.

Zovirax in tableted dosage form is not used in children under 3 years of age.

Carefully:Zovirax should be used with caution in case of dehydration and kidney failure.

Pregnancy and lactation:

Pregnancy

Analysis of treatment with acyclovir in women during pregnancy did not reveal an increase in the number of birth defects in their children compared to the general population.

However, caution should be exercised when prescribing Zovirax to women during pregnancy and assessing the intended benefit to the mother and the possible risk to the fetus.

Lactation

After taking the drug Zovirax inside at a dose of 200 mg 5 times a day acyclovir was defined in breast milk at a concentration of 60 to 410 % plasma concentration. At such concentrations in breast milk, breastfed infants may receive acyclovir in a dose up to 0.3 mg / kg / day. Given this, caution should be exercised when administering Zovirax to lactating women.

Dosing and Administration:

A drug Zovirax, pills can be taken with meals, because eating does not violate its absorption to a large extent. Tablets should be washed down with a full glass of water.

Adults

Treatment of infections caused by the herpes simplex virus

For the treatment of infections caused by the herpes simplex virus, the recommended dose of Zovirax is 200 mg 5 times a day (every 4 hours, except during the night sleep). Usually the course of treatment is 5 days, but can be prolonged with severe primary infections.

In case of severe immunodeficiency (for example, after bone marrow transplantation) or with a violation of absorption from the intestine, the dose of Zovirax for oral administration may be increased to 400 mg. Alternatively, the possibility of using Zovirax in the dosage form of lyophilizate for the preparation of a solution for infusions may be considered. Treatment should be started as soon as possible after the onset of infection; with relapses the drug is recommended to be prescribed already in the prodromal period or with the appearance of the first elements of the rash.

Prevention of recurrence of infections caused by the herpes simplex virus

To prevent the recurrence of infections caused by the herpes simplex virus, in patients with normal immune status, the recommended dose of Zovirax is 200 mg 4 times a day (every 6 hours).

A more convenient therapy scheme for 400 mg twice a day (every 12 hours) is suitable for many patients.

In some cases, lower doses of Zovirax 200 mg 3 times a day (every 8 hours) are effective, or 200 mg 2 times a day (every 12 hours).

Some patients may experience an exacerbation of the infection with a total daily dose of 800 mg.

Treatment with Zovirax should be interrupted periodically for 6-12 months to identify possible changes in the course of the disease.

Prevention of infections that caused the herpes simplex virus in patients with immunodeficiency

To prevent infections caused by the herpes simplex virus, in patients with immunodeficiency, the recommended dose of Zovirax is 200 mg 4 times a day (every 6 hours).

In case of severe immunodeficiency (for example, after bone marrow transplantation of the brain) or in the case of impaired absorption intestinal dose of Zovirax for intake can be increased to 400 mg 4 times a day. As Alternatives can be considered the possibility of using the drug Zovirax in dosage form lyophilizate for cooking solution for infusion. The duration of the preventive course of therapy is determined by the length of the period when there is risk of infection.

Treatment of varicella and herpes zoster

Long-term treatment of chicken pox and herpes zoster recommended dose of the drug Zovirax is 800 mg 5 times a day (every 4 hours, except during the night sleep). The course of treatment is 7 days.

In patients with severe immunodeficiency (eg, after bone marrow transplantation) or with intestinal absorption, consideration should be given to the possibility of prescribing Zovirax in the dosage form of lyophilizate for the preparation of a solution for infusions.

The drug should be prescribed as soon as possible after the onset of infection, since in this case the treatment is more effective.

Special patient groups

Children aged 3 years and over

Treatment of infections caused by the herpes simplex virus: prevention of infections caused by the herpes simplex virus in patients with immunodeficiency

- at the age of 3 years and older the same dose as for adults.

Treatment of chicken pox

- at the age of 6 years and older - 800 mg 4 times a day;

- at the age of 3 to 6 years - 400 mg 4 times a day.

More precisely, the dose can be determined from the calculation of 20 mg / kg body weight (but not more than 800 mg) 4 times a day. The course of treatment is 5 days.

Prevention of recurrence of infections caused by the herpes simplex virus: treatment of herpes zoster

There is no data on the dosage regimen.

Elderly patients

It is necessary to consider the likelihood of renal failure in elderly patients, the dose should be adjusted according to the degree of renal failure (see subsection "Patients with renal insufficiency ").

It is necessary to ensure the maintenance of an adequate water balance.

Patients with impaired function of night

Caution is advised when prescribing Zovirax to patients with impaired function of the night. It is necessary to ensure the maintenance of an adequate water balance.

In patients with renal insufficiency, taking acyclovir orally at the recommended doses for the treatment and prevention of infections caused by the herpes simplex virus does not result in cumulation of the drug to concentrations exceeding the established safe levels.However, in patients with creatinine clearance less than 10 ml / min, the dosage of Zovirax should be reduced to 200 mg 2 rye per day (every 12 hours).

In the treatment of varicella and herpes zoster, recommended dosages of Zovirax, tablets are:

- when creatinine clearance is less than 10 ml / min - 800 mg twice a day (every 12 hours);

- with a creatinine clearance of 10-25 ml / min - 800 mg 3 times a day (every 8 hours).

Side effects:

The following classification of unwanted reactions is used depending on the frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10), sometimes (> 1/1000, <1/100), rarely (> 1 / 10,000, <1/1000), very rarely (<1 / 10,000).

From the hematopoiesis and lymphatic system:

Rarely: Anemia, leukopenia, thrombocytopenia

From the immune system:

Rarely: Anaphylaxis

From the side of neuro-mental status:

Often: Headache, dizziness

Very rarely: Excitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic, symptoms, convulsions, drowsiness, encephalopathy, coma.

Usually, these side effects were observed in patients with renal insufficiency or in the presence of other provoking factors, were mainly reversible.

From the respiratory system, chest and mediastinum:

Rarely: Dyspnea

From the gastrointestinal tract:

Often: Nausea, vomiting, diarrhea, abdominal pain.

From the liver and biliary tract

Rarely: Reversible increase in bilirubin and hepatic enzymes in blood.

Rarely: Hepatitis, jaundice.

From the skin and subcutaneous tissue:

Often: Itching, rash, including photosensitization.

Sometimes: hives, rapid diffuse hair loss.

Since this type of alopecia is observed in various diseases and in the treatment with many drugs, its association with acyclovir is not established.

Rarely: Angioedema.

Rarely: Toxic epidermal necrolysis, multiforme exudative erythema.

From the urinary system:

Rarely: Increased levels of urea and creatinine in the blood.

Rarely: Acute renal failure, renal colic.

Renal colic can be associated with kidney failure.

Others:

Often: Fatigue, fever.

Overdose:

Symptoms

Acyclovir is only partially absorbed in the gastrointestinal tract. In case of occasional single-dose acyclovir oral doses of up to 20 g, no toxic effects are reported.With repeated doses exceeding recommended, inside for several days, there were violations of the gastrointestinal tract (nausea, vomiting) and neurologic (headache and confusion).

Sometimes there may be shortness of breath, diarrhea, impaired renal function, agitation, confusion, hallucinations, convulsive seizures, coma.

Treatment

Patients need careful medical supervision to identify possible symptoms of intoxication. Acyclovir is excreted from the body by hemodialysis, so hemodialysis can be used to develop symptoms of intoxication.

Interaction:

No clinically significant interactions were observed with Zovirax.

Acyclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar elimination route can increase the plasma concentration of acyclovir. Probenecid and cimetidine, being inhibitors of microsomal oxidation, increase the index AUC (the area under the curve "concentration in plasma - time") of acyclovir, reduce its renal clearance and increase the plasma concentration. An increase in the indicator was noted AUC for acyclovir and an inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplantology, while using both drugs simultaneously. However, dose adjustment is not required due to a wide range of therapeutic doses of acyclovir.

Special instructions:

Hydration status

Patients taking high doses of Zovirax preparation inside should receive a sufficient amount of fluid.

Older patients and patients with renal insufficiency

Patients of this group are at increased risk of developing side effects from the nervous system (usually such reactions are reversible in response to drug withdrawal), respectively, should be under close medical supervision.

Transmission of infection

All patients, especially in the presence of clinical manifestations, should be careful to avoid the potential for transmission of the virus, and patients should be informed of cases of asymptomatic virus.

Effect on the ability to drive transp. cf. and fur:

No data.

Form release / dosage:

Tablets of 200 mg.

Packaging:

For 5 tablets in a blister of PVC / PVDC / A1; 5 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store in a dry place, at a temperature below 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015206 / 01

Date of registration:16.10.2008

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GlaxoSmithKline Pharmaceuticals, S.A. Poland

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp26.06.2015

Illustrated instructions

Instructions

Zovirax ® (Zovirax®)