Valtrovir

General characteristics. Structure:

Active ingredient: valaciclovir;
1 tablet contains a valatsiklovir of a hydrochloride, in terms of валацикловир, 500 mg; excipients: povidone, calcium stearate, cellulose microcrystallic, sodium krakhmalglikolit (type A), mix for a covering of "Opadry II Yellow". Mix for a covering of "Opadry II Yellow" contains: gipromeloza; lactose, monohydrate; titanium dioxide (Е 171); polyethyleneglycol 3000 (macrogoal); triacetin; quinolinic yellow (Е 104); yellow decline of FCF (Е 110); ferrous oxide yellow (Е 172); indigo carmine (Е 132).

Pharmacological properties:

Pharmacodynamics. Valatsiklovir – antiviral drug. Is specific inhibitor of a DNA polymerase of viruses of herpes. Blocks synthesis of virus DNA and replication of viruses. In a human body валацикловир quickly and completely turns into an acyclovir by means of valatsiklovirgidrolaza enzyme. Valatsiklovir is active in vitro concerning herpes simplex viruses І and ІІ types, the Varicella zoster virus, a cytomegalovirus, Epstein-Burra's virus and a virus of herpes of the person like VІ. Owing to phosphorylation the acyclovir turns into active triphosphate of an acyclovir, kotoryykonkurentno inhibits synthesis of virus DNA. At the first stage of phosphorylation activity of virus-specific enzyme – a virus thymidinekinase which is only in virusinfitsirovanny cells is required. At a Cytomegaloviral infection phosphorylation of an acyclovir is partially carried out by specific enzyme – UL 97 phosphotransferase that substantially explains its selectivity.
Phosphorylation process (transformation of monophosphate into triphosphate) completely comes to the end with cellular enzymes. Triphosphate of an acyclovir inhibits virus DNA - a polymerase and, being a nucleoside analog, is built in virus DNA that leads to an obligate rupture of a chain, the termination of synthesis of DNA and, therefore, to blocking of replication of a virus.

Pharmacokinetics. Valatsiklovir and an acyclovir have similar pharmacokinetic parameters after intake. After intake валацикловир it is well soaked up, quickly and almost completely turns into an acyclovir and L-valine. Bioavailability of an acyclovir at reception of 1000 mg of a valatsiklovir makes 54% and does not decrease at a concomitant use of food. The maximum concentration of an acyclovir after a single dose of 250-1000 mg of a valatsiklovir makes 10-25 µmol (2,2-5,7 mkg/ml) and comes in 1-1,5 hours after reception. The maximum concentration of a valatsiklovir in plasma
comes on average in 30-60 minutes after reception and in 3 hours валацикловир in a blood plasma is not defined. Linkng of a valatsiklovir with proteins of plasma very low (15%). Elimination half-life
acyclovir (Т½) after one-time and reusable introduction of a valatsiklovir at patients with normal function of kidneys makes about 3 hours. Valatsiklovir is brought with urine mainly in the form of an acyclovir (more than 80% of a dose) and its metabolite 9-karboksi-a metoksimetilguanin, in an invariable look less than 1% of drug are removed.
At patients with an end-stage of renal failure Т½ of an acyclovir makes about 14 hours.
Pharmaceutical characteristics. Main physical and chemical properties. Tablets, film coated citreous color, with a biconvex surface, from a risky on the one hand tablet and a stamping of "KMP" on the other hand. On cross section the kernel of white color is noticeable.

Indications to use:

– Treatment of diseases of skin and the mucous membranes caused by the Herpes simplex virus, including for the first time revealed and recurrent genital herpes;
– treatment of herpes of lips (Herpes labialis);
– prevention of a recurrence of the infections caused by a herpes simplex virus (on condition of an initiation of treatment at once after emergence of the first symptoms of a disease), including damages of skin and mucous membranes;
– preventive treatment of a recurrence of infections of skin and the mucous membranes caused by a herpes simplex virus including genital herpes;
– for decrease in risk of transfer of a virus from patients with genital herpes (at Valtrovir's use as suppressive therapy in a combination with observance of rules of safe sex);
– treatment of the surrounding herpes;
– prevention of the Cytomegaloviral infection developing after organ transplantation.

Route of administration and doses:

Adults. For treatment of the infections caused by a herpes simplex virus, the adult Valtrovir appoint 500 mg 2 times a day. Treatment of a recurrence of a disease lasts 3-5 days; in case of primary disease which can proceed more hard, from 5 to 10 days. It is desirable to begin treatment in a prodromal stage or at once after emergence of the first symptoms of a disease. Treatment of herpes of lips: on 2 g 2 times a day for 1 day with an interval between receptions about 12 h, but not less than 6 h. Therapy should be begun at emergence of the first early symptoms of lip herpes (feeling of tingling, an itch or burning in lips).
Treatment of the surrounding herpes: 1000 mg of Valtrovir 3 times a day within 7 days. Treatment has to be begun as soon as possible. For prevention of a recurrence of the infections caused by a herpes simplex virus: the patient with normal immunity appoints 500 mg of 1 times a day. To some patients with very frequent aggravations (for example, 10 and more episodes in a year) the dose of 500 mg is appointed in 2 receptions (250 mg 2 times a day). The patient with an immunodeficiency appoints a dose of 500 mg 2 times a day. Reduction of transfer of a virus of genital herpes: adult heterosexual persons (with normal immunity) with genital herpes (the infected sexual partner) at which note 9 or less exacerbations of a disease within a year Valtrovir need to appoint in a dose 500 mg of 1 times a day to the infected partner. There are no data on reduction of transfer of a virus of genital herpes in other populations of patients.
For prevention of a Cytomegaloviral infection by the adult and to teenagers 12 years are more senior appoint in a dose 2 g 4 times a day as it is possible after transplantation earlier. Use duration usually makes 90 days, but can be increased for patients with a high risk.
Dosage at an impaired renal function. Valtrovir's dosage has to be changed according to degree of a renal failure, as shown below:

                         Change of a Dosage of Valtrovir function
                           Herpes simplex kidneys                                       Decrease in risk
(clearance   of Herpes              Prevention                                   of transfer of a virus at
  zoster creatinine      Treatment   Normal     Immunodefi-   genital herpes
and ml/min.)                                    immunity       tsit 

15-30        1 000 mg                                                         
                 2 times in  change  changes    changes         changes
                  days
<15       1 000   mg 500 mg of 1 times  of 250 mg of 1 times  of 500 mg of 1 times      of 250 mg of 1 times a day
               1 time in     in days           a day         a day
                  days

For treatment of Herpes labialis (oral Herpes simplex):

Clearance of creatinine, ml/min.            dosing Mode
31 - 49                                     1 g 2 times a day for 1 day
15 -                                    30 500 mg 2 times a day for 1 day
<                                        15 500 mg once

For prevention of a Cytomegaloviral infection recommend the following doses:

Clearance of creatinine, ml/min.       dosing Mode
75 and                                    higher than 2 g 4 times a day
                                         50-75 1,5 g 4 times a day
                                         25-50 1,5 g 3 times a day
                                         10-25 1,5 g 2 times a day
Lower than 10 or dialysis                    of 1,5 g of 1 times a day

At the patients who are on a hemodialysis it is recommended to apply the same dosage of Valtrovir, as to patients with clearance of creatinine less than 15 ml/min. Drug is accepted after the procedure of a hemodialysis. A dosage at the broken function of a liver. To change a dose patients with easy or moderate degree of cirrhosis have no need (the synthesizing function of a liver is kept). Pharmacokinetic indicators at the started cirrhosis cases (with disturbance of the synthesizing function of a liver and existence of signs of the portal block) testify to lack of need of change of a dosage, however clinical experience is limited.

Features of use:

Use for elderly patients. In the absence of serious violations of function of kidneys it is not necessary to change a dosage. It is necessary to support the adequate level of hydration. Correction of a dose is necessary for patients with a renal failure (see the Route of administration and doses). At patients with a renal failure and at the patients receiving Valtrovir for prevention of a Cytomegaloviral infection after organ transplantation the frequency of development of neurologic reactions is higher. Therefore with care it is necessary to apply Valtrovir at a liver failure and transplantation of a liver. There are no higher daily doses of a valatsiklovir given about use (4 mg and any more) for treatment of patients with liver diseases. Special researches concerning use of a valatsiklovir at transplantation of a liver were not conducted; however it is established that prevention by means of high doses of an acyclovir reduces the frequency of infection and a disease caused by a cytomegalovirus.
Suppressive therapy valatsikloviry reduces risk of transfer of genital herpes, but does not cure a herpes infection and completely does not exclude risk of transfer of a virus. In addition to therapy by Valtrovir it is recommended to follow the rules of safe sex.
Ability to influence speed of response at control of motor transport or work with other mechanisms. At the moment there are no such messages. However, should take with caution drug the persons managing motor transport or working with other mechanisms in connection with risk of development of possible undesirable reactions from a nervous system.

Side effects:

Criteria for evaluation of frequency of development of side reactions: very often – ≥1 on 10, it is frequent – ≥1 on 100 and ≤1 on 10, infrequently – ≥1 on 1000 and <1 on 100, is rare – ≥1 on 10 000 and <1 on 1000, is very rare – <1 on 10 000.
From TsNS: often – a headache, it is rare – reversible neurologic disturbances, such as dizziness, disturbance and confusion of consciousness, a hallucination, decrease in mental capacities, a loss of consciousness; very seldom – agitation, a tremor, an ataxy, a dysarthtia, psychotic symptoms, spasms, encephalopathy, a coma. As a rule, these symptoms have reversible character and are observed at patients of risk group.
From the alimentary system: often – nausea, it is rare – feeling of discomfort in an abdominal cavity, an abdominal pain, vomiting, diarrhea, dryness in a mouth, a meteorism, anorexia.
From gepatobiliarny system: very seldom – the tranzitorny increase in indicators of hepatic tests which sometimes is regarded as hepatitis.
From kidneys: seldom – renal failures, it is very rare – kidney pain which can be associated with a renal failure, an acute renal failure.
From system of a hemopoiesis: very seldom – a leukopenia/neutropenia (especially at patients with an immunodeficiency), thrombocytopenia.
Allergic reactions: infrequently – rash, a photosensitization, it is rare – an itch, is very rare – a small tortoiseshell, a Quincke's disease, an anaphylaxis.
Others: infrequently – an asthma. Also at the patients with an immunodeficiency receiving it is long high doses of a valatsiklovir, the renal failure, a mikroangiopatiya, hemolitic anemia and thrombocytopenia are possible (sometimes in a combination).

Interaction with other medicines:

Clinically significant forms of interaction of Valtrovir with other medicines were not noted. Cimetidinum and пробенецид is increased by AUC (the area under the pharmacokinetic curve describing dependence "concentration/time") an acyclovir by decrease in its renal clearance: nevertheless, need for change of a dose is absent in view of a wide therapeutic index of an acyclovir. Any drugs which are removed by active canalicular secretion and are appointed along with Valtrovir, can increase concentration of an acyclovir in a blood plasma.
With care and under control of function of kidneys it is necessary to apply Valtrovir along with nephrotoxic drugs, such as cyclosporine, такролимус. It is necessary to appoint with care Valtrovir in high doses (4 g a day) for prevention of a Cytomegaloviral infection along with the drugs competing with an acyclovir for ways of removal as it can lead to increase in level in a blood plasma of one or both drugs and their metabolites.
Simultaneous use of a valatsiklovir and mikofenolat of a mofetil (the immunosuppressant which is applied at organ transplantation) leads to increase in concentration of both ingredients in a blood plasma.

Contraindications:

Hypersensitivity to the valatsiklovir, an acyclovir or any other component which is a part of drug.
Use during pregnancy or feeding by a breast. Purpose of drug during pregnancy is possible only when the expected advantage for the woman exceeds potential risk for a fruit.
The acyclovir, the main metabolite of a valatsiklovir, is allocated with breast milk. Considering it, it is necessary to be careful at purpose of drug Valtrovir during feeding by a breast and to resolve an issue of a possibility of the termination of feeding by a breast. Children. There are no data on use of drug for treatment of children.

Overdose:

Symptoms. Nausea, vomiting, development of an acute renal failure, neurologic symptoms (confusion of consciousness, a hallucination, agitation, a loss of consciousness and a coma) are possible. The majority of the described symptoms are effects of an insufficient dose decline at patients with a renal failure and patients of advanced age. It is necessary to be careful at establishment of a dose.
Treatment. Patients have to be under observation for identification of signs of toxic action. The hemodialysis considerably accelerates elimination of an acyclovir from blood and can be considered as an optimum method of treatment in case of symptomatic overdose.

Storage conditions:

Period of validity 2 years. To store in the place, unavailable to children, in original packaging, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. 1 or 5 blisters No. 10 in a pack.