Pharmacological properties Valtrex:
Valtrex Valacyclovir (2 – [(2-amino-1 ,6-dihydro-6-oxo-9H-purin-9-yl) methoxy] ethyl L valinat hydrochloride) – an antiviral drug. Is a specific inhibitor of DNA polymerase of herpes viruses. Blocks the synthesis of viral DNA and viral replication. In humans, valaciclovir is converted to acyclovir and valine. Acyclovir in vitro has a specific activity against herpes simplex virus types I and II, the virus Varicella zoster, cytomegalovirus, Epstein – Barr virus and human herpesvirus type VI. As a result of phosphorylation of acyclovir triphosphate is converted to active acyclovir, competitive ingibiruyushego synthesis of viral DNA. In the first stage of phosphorylation requires the activity of virus-specific enzyme. For herpes simplex virus, Varicella zoster virus and Epstein – Barr virus thymidine kinase is, available only in cells infected with the virus. When CMV infection acyclovir phosphorylation in part by a specific enzyme, which largely explains its selectivity.
Cases of low sensitivity to acyclovir in the treatment and prophylactic use in patients with normal immune status is very rare, they occurred mainly in immunocompromised patients, such as after bone marrow transplantation and other organs in patients receiving chemotherapy for cancer, and patients infected with HIV. Drug resistance is usually associated with deficiency of thymidine kinase. Sometimes the decrease in sensitivity due to a violation or a viral thymidine kinase or DNA polymerase.
Valtrex faster pain relief in the treatment of herpes zoster reduces the duration of pain, and reduces the incidence of patients with zosterassotsiirovannoy pain, including acute and postherpetic neuralgia. Prevention of cytomegalovirus infection with Valtrex reduces the risk of acute graft rejection (patients after kidney transplantation), the incidence of opportunistic infections and other infections caused by herpes simplex virus and herpes zoster.
After oral administration valaciclovir is well absorbed from the gastrointestinal tract, is rapidly and almost completely converted to aciclovir and valine, possibly under the action of the enzyme by hydrolysis valatsiklovirgidrolazy valacyclovir. The bioavailability of acyclovir when receiving 1 g of valacyclovir is 54% and not decreasing, while eating. The maximum concentration of acyclovir after a single dose of 250 mg-1 g of valacyclovir is an average of 10-25 micromol / l (2,2-5,7 mg / ml) achieved after 1-1.5 h after administration. The maximum concentration of valaciclovir in plasma is reached after an average of 30-60 minutes after ingestion, after 3 hours and valaciclovir in plasma is not defined. The pharmacokinetics of valacyclovir and acyclovir is similar for single and repeated use. Binding of valaciclovir to plasma proteins is very low. The half-life of acyclovir after single and repeated application of approximately 3 hours Valacyclovir is excreted in urine, mainly in the form of acyclovir and its metabolite 9 carboxy methoxymethyl guanine. Zoster virus and herpes simplex virus did not significantly alter the pharmacokinetics of valacyclovir and acyclovir after oral Valtrex.
In the study of the pharmacokinetics of valacyclovir and acyclovir in the speed with trimester of pregnancy, AUC in the phase of the plateau after the application valaciclovir at a dose of 1,000 m / day was approximately 2 times higher than after application of acyclovir administered orally at a dose of 1200 mg / day.
In patients with HIV infection pharmacokinetic characteristics of acyclovir after single or repeated application at a dose of 1-2 grams of Valtrex have not changed compared with those in healthy individuals.
APPLICATION Valtrex:
The treatment of shingles: 1 g 3 times daily for 7 days, infections caused by herpes simplex virus, 500 mg 2 times / day. Treatment of recurrence of the disease lasts for 3-5 days in the case of the primary disease, which can flow more difficult, from 5 to 10 days. Treatment should begin as early as possible, for recurrent herpes simplex infections of forms – in the prodromal period or immediately after the first symptoms.
Alternatively, for the treatment of labial herpes Valtrex effectively use a dose of 2 g 2 times daily for 1 day. The second dose should be taken approximately 12 hours (no earlier than 6 h) after the first dose. In this mode dosing duration of treatment should not exceed 1 day, since it is proved that it does not increase the clinical efficacy of treatment. Therapy should be started when the first early symptoms of labial herpes (feeling tingling, itching or burning sensation in the lips).
Preventive treatment (suppression) of recurrence of infections caused by herpes simplex virus: patients with normal immune status is prescribed 500 mg 1 time a day. Some patients with very frequent exacerbations (eg, 10 or more episodes per year), a dose of 500 mg administered in 2 divided doses (250 mg 2 times a day). Patients with immunodeficiency prescribe a dose of 500 mg 2 times a day.
Reducing transmission of genital herpes: the adult heterosexual persons with normal immunity to genital herpes (an infected sexual partner), all of whom had at least 9 or exacerbations of the disease within a year, Valtrex is prescribed in doses of 500 mg 1 time a day infected partner. Data to reduce transmission of genital herpes in patients with no other populations.
Prevention of cytomegalovirus infection and disease: adults and adolescents (aged over 12 years) Valtrex is prescribed at a dose of 2 g 4 times a day as soon as possible after transplantation. In renal failure dose is reduced. The treatment duration is typically 90 days but can be increased in patients with high risk.
Dosage adjustment in patients with impaired renal function
Must carefully prescribe valaciclovir for patients with impaired renal function. Be sure to maintain an adequate level of hydration of the body.
Patients on hemodialysis, Valtrex is recommended to use the same dose as patients with creatinine clearance below 15 ml / min of drug taking after hemodialysis.
Prevention of cytomegalovirus infection:
Creatinine clearance, ml / min: 75 and above - 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
Less than 10 or dialysis – 1.5 g of 1 time per day
Creatinine clearance should be constantly monitored, especially at a time when renal function may change rapidly, such as immediately after transplantation. Accordingly, the dose should be corrected by Valtrex.
Dispensing with abnormal liver function
No need for dose adjustment in patients with liver cirrhosis mild or moderate severity. Indicators of pharmacokinetics in advanced cirrhosis (in violation of the synthesizing function of liver and signs of portal hypertension) did not indicate the need for correction of dosing, but clinical experience with the drug in this group of patients is limited.
Children: data on the use of the drug have no children.
Patients with advanced age: elderly patients with no marked changes in renal function to change the dose is not recommended. The possibility of renal dysfunction in a patient should be considered and the dosage adjusted accordingly. Necessary to maintain an adequate level of hydration of the body.
CONTRAINDICATIONS Valtrex:
Hypersensitivity to valacyclovir, acyclovir or other ingredients.
SIDE EFFECTS Valtrex:
The following information about the side effects are classified according to organs and systems, the frequency of occurrence and are divided into categories:
very often ≥ 1 to 10, often ≥ 1 100 and <1 to 10, rarely ≥ 1 in 1000 and <1 to 100, rarely ≥ 1 in 10 000 and <1 in 1000, very rare <1 in 10 000.
According to clinical studies
Nervous system disorders: frequent – a headache.
Gastrointestinal disorders: Frequent – nausea.
According to post-licensure surveillance
In the blood and lymphatic system: very rare – leukopenia, and thrombocytopenia. Leukopenia primarily detected in immunocompromised patients.
By the immune system: very rare – anaphylaxis.
The nervous system and mental disorders: rarely – dizziness, and confusion, hallucinations, loss of consciousness is very rare – agitation, tremor, ataxia, disartriya, psychotic symptoms, seizures, encephalopathy, coma.
These symptoms are in most cases are reversible and will mark them, mainly in patients with renal insufficiency or other risk factors (see APPLICATION). In patients after organ transplantation, receiving Valtrex for CMV prophylaxis in high doses (8 g per day), neurological reactions occur more frequently than those receiving lower doses.
The respiratory system and chest cavity: Infrequent – shortness of breath.
Gastrointestinal: rare – abdominal discomfort, vomiting, diarrhea.
Hepatobiliary system: very rare – a reversible increase in liver function tests are sometimes judged as hepatitis.
Skin and subcutaneous tissue disorders: rare – skin rashes, including photosensitivity phenomenon, rarely – itching and very rarely – urticaria, angioedema.
The kidneys and urinary system: rarely – renal dysfunction is very rare – acute renal failure.
Other: there are reports of kidney failure, microangiopathy, hemolytic anemia and thrombocytopenia (sometimes in combination) in a clinical trial in severely immunocompromised patients, especially in patients with advanced HIV infection receiving high-dose (8 g per day) for valaciclovir a long time. The same phenomenon was seen in patients not treated with valacyclovir, but with similar conditions.
SPECIAL INSTRUCTIONS Valtrex:
Special caution.
Hydration: elderly patients during treatment Valtrex should increase fluid intake. In the absence of marked renal dysfunction correct dosing regimen is not required.
Use in renal impairment and elderly patients. Acyclovir is eliminated via the kidneys, in connection with the elderly patients with a probability of decline in renal function is necessary to reduce the dose. Patients with a history of kidney disease in the risk of neurologic complications increases, and with a view to early identification of such patients be carefully monitored. According to reports, these reactions are mostly reversible and disappear after discontinuation of treatment. (See ADVERSE REACTIONS).
The use of higher doses of Valtrex with liver failure and liver transplantation: data on the use of higher doses of Valtrex (4 mg or more per day) for the treatment of patients with liver disease do not. It is therefore necessary with caution to a higher dose of the drug in such patients. Specific studies on the use of Valtrex for liver transplantation is not performed, but it was found that prophylaxis with high-dose acyclovir reduces the incidence of CMV infection and disease infection.
Reducing transmission of genital herpes: suppressive therapy with valacyclovir reduces the risk of transmission of genital herpes, but does not cure herpes infections and do not completely eliminate the risk of transmission. In addition to medication Valtrex is recommended to follow the rules of safe sex.
During pregnancy and lactation. Data on the use of Valtrex during pregnancy are limited, so Valtrex can be used only when the expected benefit of therapy outweighs the potential risk to the fetus. Conducted surveillance of pregnant women taking valacyclovir, or any form of acyclovir (the active metabolite of valacyclovir): 111 and 1246 women, respectively (29 and 756 pregnant women taking valacyclovir, respectively, or any form of acyclovir in the first trimester of pregnancy). Neither congenital effect was not unique or consistent, so you can determine why they occur. Embryotoxic and teratogenic effects were detected, compared with a control group of patients, but given the small number of observed, true and final conclusion about the safety of valaciclovir in pregnancy can be done.
Lactation. Acyclovir, valacyclovir main metabolite, determined in breast milk. As a result of daily application of 500 mg of valacyclovir average maximum concentration of acyclovir in breast milk differed from 0.5 to 2.3 (average 1.4) times the concentration of acyclovir in plasma of the mother. The relationship between the concentration of acyclovir in breast milk and blood plasma of the mother is from 1.4 to 2.6 (average 2.2). The average concentration of acyclovir in breast milk was 2.24 mg / ml (9.95 mmol). If you are receiving valaciclovir mother in a dose of 500 mg 2 times a day the child through breast milk receive a dose of 0.61 mg of acyclovir / kg per day. The half-life of acyclovir in breast milk is similar to that of blood plasma. Valacyclovir unchanged in plasma mothers, breast milk or urine of an infant is not determined.
We recommend Valtrex with caution by women during lactation. However, acyclovir is used to treat infants with infections caused by herpes simplex virus, by / in the introduction to the doses of 30 mg / kg per day.
Effect on ability to drive motor vehicles and other machines. Special warnings not.
INTERACTION Valtrex:
signs of clinically significant drug interactions have been identified.
Acyclovir appears mainly unchanged in the urine by active tubular secretion. Any medications given concurrently with Valtrex and with this inference, may increase the concentration of acyclovir in plasma.
Cimetidine and probenecid increases value of AUC of acyclovir by reducing its renal clearance, however, there is no need for dose adjustment because of the wide therapeutic index of acyclovir.
Caution must be exercised by giving high doses of Valtrex (4 g / d) for the prevention of cytomegalovirus infection in conjunction with drugs which compete with aciclovir for elimination pathway, as this could lead to increased plasma levels of one or both drugs and their metabolites. At the same time taking with mycophenolate mofetilom (immunosuppressive drugs used in organ transplants) in blood plasma increases the level of acyclovir and mycophenolate mofetil inactive metabolite. It should also keep careful while appointing high doses of Valtrex and other drugs that affect renal function (eg cyclosporine, tacrolimus).
Overdose Valtrex:
Symptoms
Cases of acute renal failure and neurological symptoms including confusion, hallucinations, agitation, loss of consciousness and coma in patients with an overdose of valacyclovir, also noted nausea and vomiting. To prevent inadvertent overdose must adhere caution when using the drug. Many of the reported cases of repeated overdose in patients with impaired renal function and elderly patients were due to insufficient reduction of the dose.
Treatment
Patients should be carefully monitoring for timely diagnosis of toxic manifestations. Hemodialysis removal of acyclovir significantly faster from the blood and can be considered the best method of treatment in the event of symptomatic overdose.
