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

Excipients: cellulose microcrystalline (PH 101) 109.425 mg, crospovidone 7 mg, dye indigo carmine (E132) 0.3 mg, povidone (K 30) 18 mg, povidone (K 90D) 2 mg, magnesium stearate 7 mg, purified water q.s.*

Film Sheath: coloring Opadrai 02C50740 blue 21 mg, purified water q.s.*

The composition of the dye Opadrai 02C50740 blue: (E464) 13.02 mg, titanium dioxide (E171) 5.46 mg, macrogol / PEG 400 1.05 mg, macrogol / PEG 6000 0.63 mg, indigo carmine dye (E132) 0.42 mg, polysorbate 80 (E433) 0.42 mg.

* evaporates in the production process

Description:From light blue to blue, oval, biconvex tablets covered with a film membrane; on one side of the tablets engraving "V" and "5" on opposite sides of the risks and incisions on both sides of the risks; two layers are visible on the cross section: a blue shell and a white core with blue patches.

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

J.05.A.B.11 Valaciclovir

J.05.A.B Nucleosides and nucleotides

Pharmacodynamics:

Valacyclovir: (28) - [2- [2-Amino-6-oxo-1,6-dihydro-9H-purin-9-yl) methoxy] ethyl] -2-amino-3-methylbutanoate hydrochloride is an antiviral drug. Blocks the synthesis of viral DNA and virus replication. In the human body valaciclovir turns into acyclovir and valine. Acyclovir in vitro has a specific activity in relation to herpes simplex virus type I and II, virus Varicella zoster, cytomegalovirus, Epstein-Barr virus and human herpesvirus type VI.Due to phosphorylation acyclovir is converted into active triphosphate acyclovir, competitively inhibiting the synthesis of viral DNA. At the first stage of phosphorylation, the activity of the virus-specific enzyme is necessary. For herpes simplex virus, virus Varicella zoster and the Epstein-Barr virus is a viral thymidine kinase found only in cells infected with the virus. With cytomegalovirus infection, the phosphorylation of acyclovir is mediated by the product of the phosphotransferase gene UL97.

Pharmacokinetics:

After oral administration valaciclovir is well absorbed in the gastrointestinal tract (GIT), quickly and almost completely turns into acyclovir and valine. Bioavailability of acyclovir when taking 1 g of valaciclovir is 54% and does not decrease with simultaneous intake of food. The maximum concentration of acyclovir after a single dose of 250 mg - 1 g of valaciclovir is on average 15-25 μmol / l and is achieved 1.6-2.1 hours after administration; in 3 hours valaciclovir in the blood plasma is not determined. Binding of valaciclovir to plasma proteins is 13-18%.

The half-life of acyclovir after a single and repeated application is approximately 3 hours. Valaciclovir is excreted by the kidneys, mainly in the form of acyclovir and its metabolite 9-carboxymethoxymethylguanine.

Acyclovir is widely distributed in tissues and body fluids, including the brain, kidneys, lungs, liver, watery moisture, tear fluid, intestines, muscles, spleen, uterus, mucous membrane and vaginal secretion, sperm, amniotic fluid, cerebrospinal fluid (CSF) ( 50% of the concentration in the plasma), the liquid of herpetic vesicles. The highest concentrations are created in the kidneys, liver and intestines. Penetrates through the placenta and into breast milk.

Indications:

In adults: herpes lips, genital herpes (primary and recurrent infection, prolonged suppressive therapy of recurrent genital herpes in people with immunodeficiency, including HIV infection, reducing the risk of transmission of infection to the sexual partner); herpes zoster.

Have adults and children over 12 years of age: prevention of cytomegalovirus infection in organ transplantation.

Contraindications:

Hypersensitivity, HIV infection with CD4 + lymphocyte content less than 100 / mm3, children's age (up to 12 years with cytomegalovirus infection (CMV), up to 18 years - for other indications).

Carefully:

Hepatic / renal failure, pregnancy, lactation, children and the elderly, hypohydration, simultaneous use of nephrotoxic drugs.

Pregnancy and lactation:

There are limited data on the use of valacyclovir in pregnancy.

Valacyclovir is used only in cases where the potential benefit to the mother exceeds the possible risk to the fetus.

Registered data on the outcome of pregnancy in women who took valaciclovir or acyclovir, which is an active metabolite of valacyclovir, did not show an increase in the number of birth defects in their children compared to the general population. Because the register includes a small number of women who valaciclovir when pregnancy, it is impossible to make reliable and definite conclusions about the safety of valaciclovir during pregnancy.

Acyclovir, the main metabolite of valacyclovir, is excreted in breast milk. After taking valaciclovir inside at a dose of 500 mg FROM_maxAcyclovir in breast milk in 0,5-2,3 times (on average, 1,4 times) exceeded the corresponding concentrations of acyclovir in the blood plasma of the mother.The ratio of the area under the concentration-time curve (AUC) in the blood plasma of acyclovir in breast milk to the area under the concentration-time curve (AUC) of acyclovir in the mother plasma ranged from 1.4 to 2.6 (mean 2 , 2). The mean concentration of acyclovir in breast milk was 2.24 μg / ml (9.95 μg / M). When a valaciclovir mother is taken inside at a dose of 500 mg 2 times / day, the child will undergo the same effect of acyclovir as if taking it inside at a dose of about 0.61 mg / kg / day. The half-life (T_1/2) of acyclovir from breast milk is the same as from plasma of blood. Valaciclovir in unmodified form was not determined in the plasma of the mother, breast milk or in the urine of the child.

During the period of breastfeeding the drug is used only if the intended benefit to the mother exceeds the potential risk for the child. Given this, caution should be exercised valaciclovir mother during lactation (breastfeeding). However, intravenous (IV) administration of acyclovir in a dose of 30 mg / kg / day is used in neonates for the treatment of diseases caused by the herpes simplex virus.

AT experimental research valaciclovir did not have a teratogenic effect in rats and rabbits. Subcutaneous (sc) administration of acyclovir in conventional tests for Teratogenicity did not cause teratogenic effects in rats and rabbits. In additional studies in rats, fetal abnormalities were detected with the sc administration of the drug in doses that caused an increase in the plasma concentration of acyclovir to 100 μg / ml and toxic effects in the mother.

When taken orally valaciclovir did not cause fertility disorders in males and female rats.

Dosing and Administration:

Inside (regardless of food intake).

For treatment of herpes zoster adults are prescribed 1 g 3 times / day. within 7 days.

For the treatment of diseases caused by the virus Herpes simplex adults valaciclovir prescribe 500 mg 2 times / day. In case of relapse, treatment should be given within 3 or 5 days. In more severe primary cases, treatment should be started as early as possible, and its duration should be increased from 5 to 10 days. When relapses of the disease is optimal, the appointment of valaciclovir in the prodromal period or immediately after the appearance of the first symptoms of the disease.

As an alternative for treatment herpes lips (labial fever) effective administration of valaciclovir in a dose of 2 g 2 times for 1 day. The second dose should be taken after approximately 12 hours (but not earlier than 6 hours) after taking the first dose. With this dosage regimen, the duration of treatment should not exceed 1 day, as it does not provide additional clinical benefits. Therapy should be started when the earliest symptoms of a labial fever occur (ie, tingling, itching, burning).

For prevention (suppression) of recurrences of infections caused by the virus Herpes simplex, adults with normal immunity are prescribed in a dose of 500 mg 1 time / day. Adults with immunodeficiency recommended to appoint 500 mg 2 times / day. The duration of treatment is 4-12 months. Data on the prevention of infection in other populations of patients are absent.

When renal failure the dosage regimen is set depending on the creatinine clearance (CK) and the indications.

Indications	CK (ml / min)	Valacyclovir dose
Shingles Herpes	15-30 ml / min	1 g 2 times / day.
Shingles Herpes	less than 15 ml / min	1 g 1 time / day.
Treatment of infections caused by Herpes simplex	less than 15 ml / min	500 mg once a day.
Treatment of labial herpes	31-49 ml / min	1 g 2 times for 1 day
	15-30 ml / min	500 mg twice a day. within 1 day
	less than 15 ml / min	500 mg once
Prevention (suppression) of infections caused by Herpes simplex	less than 15 ml / min	at a normal state of immunity: 250 mg 1 time / day
	less than 15 ml / min	with immunodeficiency: 500 mg 1 time / day
To reduce infection with genital herpes	less than 15 ml / min	250 mg 1 time / day

Patients who are on hemodialysis, it is recommended to appoint valaciclovir immediately after the end of the hemodialysis session in a dose intended for patients with SC less than 15 ml / min. The drug should be used after the end of the hemodialysis session.

For prevention of cytomegalovirus infection in adults and adolescents over 12 years, the recommended dose is 2 g 4 times / day. The drug is prescribed as soon as possible after the transplantation. The dose should be reduced depending on the creatinine clearance (CK). The course duration is 90 days, but can be increased in patients with a high risk of infection.

Creatinine clearance (ml / min)	Valacyclovir dose
≥75	2 g 4 times / day.
50 - <75	1.5 g 4 times / day.
25 - < 50	1.5 g 3 times / day.
10 - <25	1.5 g 2 times / day.
<10 or hemodialysis	1.5 grams once a day.

Frequent monitoring of QC is necessary, especially during the period when the kidney function changes rapidly (including immediately after transplantation or transplant engraftment); The dose of valacyclovir should be adjusted in accordance with QC.

Side effects:

According to the frequency, side effects are divided according to the criteria of the World Health Organization (WHO) into the following categories: very often (≥1: 10), often (≥1: 100 and <1:10), infrequently (≥1: 1000 and <1: 100 ), rarely (≥1: 10000 and <1: 1000), very rarely, including individual cases (<1: 10000).

Clinical Trials Data

Disturbances from the nervous system

Often: headache.

Disorders from the gastrointestinal tract

Often: nausea.

Post-marketing research data

Violations by the blood system and hematopoiesis

Very rarely: leukopenia, thrombocytopenia. Basically, leukopenia was observed in patients with reduced immunity.

Immune system disorders

Very rarely: anaphylaxis.

Disorders from the nervous system and the psyche

Rarely: dizziness, confusion consciousness, hallucinations, oppression of consciousness.

Very rarely: agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma.The above symptoms are mostly reversible and are usually observed in patients with impaired renal function or against a background of other predisposing conditions. In adult patients with transplanted organ, receiving high doses of acyclovir (8 g per day) for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses.

Disturbances from the respiratory system and mediastinal organs

Infrequent: shortness of breath.

Disorders from the gastrointestinal tract

Rarely: abdominal discomfort, vomiting, diarrhea.

Disturbances from the liver and bile ducts

Very rarely: reversible violations functional hepatic tests, which are sometimes regarded as manifestations of hepatitis.

Disturbances from the skin and subcutaneous fat

Infrequent: rashes, including photosensitivity.

Rarely: itching.

Very rarely: urticaria, angioedema.

Infringements from urinary system

Infrequently: hematuria (often associated with other disorders of the kidneys).

Rarely: impaired renal function.

Very rarely: acute renal insufficiency, renal colic. Renal colic can be associated with impaired renal function. Cases of precipitation of acyclovir crystals in the lumen of renal tubules have been reported. Adequate drinking regimen should be observed during treatment.

Other: In patients with severe impaired immunity, especially in adult patients with advanced HIV infection receiving high doses of acyclovir (8 g daily) for a long period of time, cases of renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia (sometimes in combination). Similar complications were observed in patients with the same underlying / or concomitant diseases, but not receiving valaciclovir.

Overdose:

Symptomatology

The onset of acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, loss of consciousness and to whom in patients with overdose of valaciclovir, nausea and vomiting. To prevent an overdose, be careful when using the drug. Many of the described cases of repeated overdose in patients with impaired renal function and in elderly patients were caused by an insufficient dose reduction.

Treatment

Patients should be closely monitored for the timely diagnosis of toxic manifestations. Hemodialysis significantly accelerates the excretion of acyclovir from the blood and can be considered the optimal method of treatment in case of symptomatic overdose

Interaction:

Clinically significant interactions are not established.

Acyclovir is excreted by the kidneys, mainly in unmodified form through active renal secretion. Combined use of drugs with this removal mechanism can lead to an increase in the concentration of acyclovir in the blood plasma.

After using acyclovir in a dose of 1000 mg and drugs cimetidine, probenecid, which are derived in the same way as acyclovir, there is an increase AUC acyclovir and, thus, decreases the renal clearance of acyclovir. However, due to the wide therapeutic index of acyclovir, dose adjustment of valacyclovir is not required.

In the treatment of labial herpes, the prevention and treatment of diseases caused by CMV, caution should be exercised in case of simultaneous use of acyclovir in higher doses (4 grams per day and above) and drugs,which compete with acyclovir for the route of excretion, because there is a potential threat of an increase in plasma concentrations of one or both drugs or their metabolites. An increase was noted AUC acyclovir and an inactive metabolite of mycophenolate mofetil (immunosuppressant, used in patients after organ transplantation) with simultaneous use of these drugs.

Simultaneous use of the drug acyclovir with nephrotoxic drugs, including aminoglycosides, organic platinum compounds, iodinated contrast medium, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be performed with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.

Special instructions:

Hydration. Older patients, persons with dehydration during treatment with valaciclovir, need to increase the amount of fluid consumed. In the absence of severe renal dysfunction, correction of the dosing regimen is not required.

Use in cases of impaired renal function and in elderly patients. Valaciclovir is excreted through the kidneys, in connection with this elderly patient with a probability of reducing kidney function, it is necessary to reduce the dose of the drug. In patients with renal pathology, the risk of developing nephrologic complications increases, and for the purpose of their timely detection, such patients should be closely monitored.

Reduction of transmission of the virus of genital herpes. Suppressive therapy with valacyclovir reduces the risk of transmission of genital herpes, but does not cure herpes infection and does not completely exclude the risk of transmission of the virus, it is recommended to avoid sexual contact.

The period of breastfeeding. It is recommended that caution be given valaciclovir women during lactation.

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

There are no special caveats. When there are side effects from the central nervous system (including agitation, hallucinations, confusion, delusions, convulsions and encephalopathy), the drug is canceled.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:10 tablets in a blister of aluminum foil and PVC / PVDH film.

1, 2, 3 and 4 blisters with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001250

Date of registration:21.11.2011 / 21.06.2016

Expiration Date:21.11.2016

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp05.02.2017

Illustrated instructions

Instructions

Vairova (Vayrova)