Valavir

General characteristics. Structure:

Active ingredient: valaciclovir;

1 tablet contains a valatsiklovir of a hydrochloride of 556 mg in terms of валацикловир 100% anhydrous substance of 500 mg;

excipients: cellulose microcrystallic (101), povidone, silicon dioxide colloid anhydrous, кросповидон, magnesium stearate; structure of a cover: Sepifilm 050 (methylhydroxypropyl cellulose, cellulose microcrystallic, acetylated (or acetates of esters) mono - and diglycerides), кандурин.

Pharmacological properties:

Pharmacodynamics. Valatsiklovir – L-valinovy ether of an acyclovir which is an analog of a purine (guanine) nucleoside. In a liver by means of a valatsiklovirgidrolaza валацикловир turns into an acyclovir and valine. An acyclovir – specific inhibitor of viruses of herpes with activity of invitro against viruses of a herpes simplex of I and II type, the Varicellazoster virus, a cytomegalovirus, Epstein-Burra's virus and a virus of herpes of the person of the VI type. An active form of an acyclovir is an acyclovir triphosphate which is formed by phosphorylation with participation of cellular kinases (a virus thymidinekinase (shopping mall)). Activation of an acyclovir specific virus enzyme substantially explains its selectivity. An acyclovir triphosphate competitively inhibits a virus DNA polymerase and is incorporated in virus DNA.

Resistance is caused by deficit of a thymidinekinase virus that leads to excessive spread of a virus in the owner's organism. Sometimes decrease in sensitivity to an acyclovir is caused by emergence of virus strains with the broken structure virus shopping mall or DNA polymerases.

With normal immunity the virus with reduced sensitivity to an acyclovir occurs at patients exclusively seldom and sometimes comes to light only at patients with heavy disturbance of immunity.

Pharmacokinetics. Valatsiklovir is well soaked up, quickly and almost completely turns into an acyclovir and valine.

Bioavailability of an acyclovir at reception of 1 g of a valatsiklovir makes 54% irrespective of meal. Average peak concentration of an acyclovir makes 10-37 µmol (2,2-8,3 mkg/ml) after use of a single dose of 250-2000 mg in 1-2 hours after use. Peak concentration of a valatsiklovir in plasma makes 4% of concentration of an acyclovir and is reached on average in 30-100 minutes, and in 3 hours decreases to below the measured quantities. Pharmacokinetic parameters of a valatsiklovir and acyclovir after one-time and repeated introduction are similar. Linkng of a valatsiklovir with proteins of plasma very low – 15%.

The elimination half-life of an acyclovir makes about 3 hours, patients with an end-stage of a renal failure approximately have 14 hours. Valatsiklovir is brought with urine, mainly in the form of an acyclovir (more than 80% of a dose) and its metabolite a 9-karboksimetoksimetilguanin.

At recipients of transplants of bodies which received валацикловир in a dose 2 000 mg 4 times a day the maximum concentration of an acyclovir equaled or exceeded such at healthy volunteers who received the same dose of drug, and daily indicators of the area under a curve "concentration time" were considerably big.
Pharmaceutical characteristics.

Main physical and chemical properties: tablets of oblong shape with a biconvex surface, with risky, covered with a film nacreous cover, almost white color.

Indications to use:

Treatment of the surrounding herpes (herpes zoster).
Treatment of infections of skin and the mucous membranes caused by a herpes simplex virus including primary and recurrent genital herpes.
Treatment of labial herpes (lip fever).
Preventive treatment (suppression) of a recurrence of infections of skin and the mucous membranes caused by a herpes simplex virus including genital herpes.
Reduction of transfer of a virus of genital herpes to the healthy partner at Valavir's use as suppressive therapy on condition of observance of rules of safe sex.
Prevention of a Cytomegaloviral infection and diseases after organ transplantation.

Route of administration and doses:

Treatment of the surrounding herpes: 1000 mg (2 tablets) of Valavir 3 times a day for        7 days.

Treatment of the infections caused by a herpes simplex virus: 500 mg (1 tablet) of Valavir 2 times a day. A course of treatment of recurrent cases - 3 or 5 days. At primary course of a disease which can be heavy treatment needs to be prolonged from 5 to 10 days. Treatment should be begun as soon as possible. At a recurrence of an infection it is desirable to use drug in a prodromal stage or at once after emergence of the first symptoms. Valavir can prevent development of defeats at an infection recurrence if treatment is begun at once after emergence of the first symptoms of a disease.

Alternatively for treatment of labial herpes an effective dose of Valavir is 2000 mg (4 tablets) 2 times a day within 1 day. The second dose should be accepted approximately in 12 hours (not earlier than in 6 hours) after reception of the first dose. At such mode of dosing duration of treatment has to be no more than 1 day as more prolonged use does not increase clinical performance of treatment. Treatment should be begun at emergence of the first early symptoms of labial herpes (feeling of tingling, an itch or burning in lips).

Suppression of the recurrence of an infection caused by a herpes simplex virus:
sick with normal immunity appoint 500 mg (1 tablet) of Valavir once a day;
appoint sick with an immunodeficiency 500 mg (1 tablet) 2 times a day.

Reduction of transfer of a virus of genital herpes. To adult heterosexualists with normal immunity at whom to 9 aggravations a year, Valavir appoint in a dose 500 mg once a day.

There are no data on reduction of transfer of a virus of genital herpes in other populations of patients.

Prevention of a Cytomegaloviral infection. To adults and teenagers Valavir is more senior than 12 years appoint in a dose 2000 mg (4 tablets) 4 times a day as soon as possible after transplantation. At a renal failure the dose is reduced. Duration of treatment makes usually 90 days, but can be increased for patients with a high risk.

Dosing at disturbances of functions of kidneys. It is necessary to appoint carefully валацикловир the patient with disturbances of functions of kidneys. Surely it is necessary to support the adequate level of hydration of an organism. The mode of dosing depends on clearance of creatinine and indications.

Treatment and prevention of the infections caused by the Herpes zoster virus and a virus of a herpes simplex

Therapeutic indications           Clearance of creatinine, ml/min.              Valavir's Dose
                                               Herpes zoster 15-30                            of 1000 mg 2 times a day
                                                                It is less than 15                        1000 mg once a day
Herpes simplex (treatment)                                                   is Less than 15 500 mg once a day
Herpes labialis (treatment)                               of 31-49                           1000 mg 2 times within 1 day
                                                                                                 15-30 500 mg 2 times within 1 day
                                                                                          It is less than 15 500 mg once
Herpes simplex (prevention)
 
- normal immunity                                                    is Less than 15 250 mg * once a day
- the immunodeficiency                                                                is Less than 15 500 mg once a day

Reduction of transfer of a virus

Herpes genitalis                                                                  is Less than 15 250 mg * once a day

* Use drug in the corresponding dosage.

Patients who are on a hemodialysis are recommended to apply the same doses of Valavir, as patients with clearance of creatinine is less than 15 have some. The dose has to be appointed after carrying out a hemodialysis.

Prevention of a Cytomegaloviral infection

Clearance of creatinine, ml/min.                           Valavir's Dose

75 and                                              more than 2000 mg 4 times a day
From 50 to 75                                               1500 mg 4 times a day
From 25 to 50                                                1500 mg 3 times a day
From 10 to 25                                                1500 mg 2 times a day
Less than 10 or dialysis                                of 1500 mg once a day

To patients who are on a hemodialysis Valavir appoint after holding a session of a hemodialysis. The clearance of creatinine has to be controlled constantly, especially during the periods when function of kidneys can change quickly, for example, right after transplantation. Respectively it is necessary to change Valavir's dose.

Dosing at disturbances of functions of a liver. To change a dose the patient with easy or moderate degree of cirrhosis there is no need (the synthesizing function of a liver is kept). Clinical experience of use of drug at late stages of cirrhosis (with disturbance of the synthesizing function of a liver and existence of signs of the portal block) is limited, but indicators of pharmacokinetics testify to lack of need to change a dose. There are no higher doses given about use (4000 mg and any more in day).

Patients of advanced age. Valavir's dose demands correction to avoid possible renal failures. It is necessary to support the adequate level of hydration of an organism.

Features of use:

Use during pregnancy or feeding by a breast.

Valavir's use during pregnancy or feeding by a breast perhaps if the potential advantage of treatment exceeds potential risk for a fruit or the child.
Children.

Children do not have experience of use of drug therefore you should not appoint drug of this age category of patients. For prevention of a Cytomegaloviral infection drug is appointed to children 12 years are more senior.

Hydration. It is necessary to support the adequate level of liquid which is entered, patients with the increased risk have dehydrations, especially at patients of advanced age.

Use at disturbances of functions of kidneys and the patient of advanced age. Valatsiklovir is brought by kidneys therefore the dose of a valatsiklovir should be reduced the patient with disturbances of functions of kidneys (see the section "Route of Administration and Doses"). At patients of advanced age function of kidneys therefore dose adjustment is necessary for them is reduced. At patients with disturbances of functions of kidneys and at patients of advanced age the risk of development of neurologic complications therefore they are subject to careful medical observation increases.

The above-stated reactions, in most cases after the treatment termination, are reversible.

There are no higher doses given concerning use (4 mg and any more in days) Valavir at a liver failure and transplantation of a liver. Therefore it is necessary to appoint with care higher doses of Valavir such patient. It was established that prevention by means of high doses of a valatsiklovir reduces the frequency of infection and the diseases caused by a cytomegalovirus.

Reduction of transfer of a virus of genital herpes. Supressivny therapy valatsikloviry reduces risk of transfer of genital herpes. It does not cure a herpes infection, and also completely does not exclude risk of transfer of a virus. In addition to therapy by Valavir observance by patients of rules of safe sex is recommended.
Ability to influence speed of response at control of motor transport or work with other mechanisms.

There are no data on a negative impact on the speed of psychomotor reactions, but it is necessary to consider a clinical condition of the patient and possible side effects during administration of drug.

Side effects:

On emergence frequency side reactions are divided into such categories: very often (≥1/10), it is frequent (≥1/100 and <1/10), infrequently (≥1/1000 and <1/100), is rare (≥1/10000 and <1/1000), is very rare (<1/10000).

Nervous system and mental disorders: often – a headache; seldom – dizziness, confusion of consciousness, a hallucination, decrease in mental capacities; very seldom – excitement, a tremor, an ataxy, a dysarthtia, psychotic symptoms, convulsions, encephalopathy, a coma.

Digestive tract: often – nausea; seldom – discomfort in a stomach, vomiting, diarrhea.

Gepatobiliarny system: very seldom – reversible increase in level of hepatic tests. Periodically it is described as hepatitis.

Blood and lymphatic system: very seldom – a leukopenia, thrombocytopenia. The leukopenia is mainly observed at patients with an immunodeficiency.

Immune system: very seldom – an anaphylaxis.

Respiratory system and bodies of a chest cavity: infrequently – an asthma.

Skin and hypodermic fabrics: infrequently – rash, including the photosensitization phenomena; seldom - an itch; very seldom – a small tortoiseshell, a Quincke's disease.

Kidneys and urinary system: seldom – a renal failure; very seldom – an acute renal failure, pain in kidneys. Pain in kidneys can be associated with a renal failure.

Another: there are messages on a renal failure, mikroangiopatichesky hemolitic anemia and thrombocytopenia (sometimes in a combination) at heavy patients with an immunodeficiency, especially at patients with late stages of HIV infection which received high doses (8000 mg a day) a valatsiklovira throughout a long time. These phenomena were noticed at patients with the same diseases, but which were not treated valatsikloviry.

Interaction with other medicines:

Any clinically significant forms of interaction were not revealed.

Valatsiklovir is brought with urine due to active canalicular secretion therefore other medicines which compete for this mechanism of removal are capable to increase concentration, to lead to increase in level in plasma of one or both drugs and their metabolites.

Cimetidinum, пробенецид reduce renal clearance of an acyclovir a little, nevertheless there is no need for drug dose adjustment.

At simultaneous use from a mikofenolat mofetily (the immunosuppressive drug which is applied after organ transplantation) the level of an acyclovir and inactive metabolite of a mikofenolat of a mofetil in plasma increases.

It is necessary to be careful also at co-administration of high doses of Valavir (4 g and more) and other drugs influencing function of kidneys (for example cyclosporine, a takrolimus).

Contraindications:

Hypersensitivity to components of drug and to an acyclovir.

Overdose:

Symptoms: nausea, vomiting, development of an acute renal failure and neurologic symptoms, including confusion of consciousness, a hallucination, agitation, a loss of consciousness and a coma.

Treatment: symptomatic, hemodialysis.

Storage conditions:

Period of validity. 2 years. Not to use drug after the termination of the period of validity specified on packaging. To store in the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 6 tablets in the blister, on 7 blisters enclosed in a pack.

On 10 tablets in the blister enclosed in a pack.