In humans, valacyclovir is rapidly and completely trenbolone enanthate for sale converted to acyclovir under the influence valatsikpovirgidrolazy enzyme. Acyclovir has in vitro a specific inhibitory activity against herpes simplex virus (HSV) 1 st and 2 nd type, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus type 6 . Acyclovir inhibits viral DNA synthesis immediately after phosphorylation and conversion to the active form of acyclovir triphosphate.The first stage of phosphorylation requires the activity of a virus-specific trenbolone enanthate for sale enzyme. For HSV, VZV and EBV this enzyme is the viral thymidine kinase, which is present in infected cells by the virus. Partial selectivity of phosphorylation is maintained in CMV and mediated through the phosphotransferase gene product of UL 97. Activation of acyclovir specific viral enzyme, to a great extent explains its selectivity.
The process of phosphorylation of acyclovir (conversion from mono- to triphosphate) by cellular kinases completed. Acyclovir triphosphate competitively inhibits viral DNA polymerase and being a nucleoside analog, is incorporated into the viral DNA, which leads to obligate rupture chain termination of DNA synthesis and therefore to block replication of the virus.
In patients with immunocompetent HSV and VZV with reduced sensitivity to valatsikpoviru are extremely rare, but sometimes can be detected in patients with severe immune disorders, eg, bone marrow transplant patients receiving chemotherapy for malignant tumors and in HIV-infected. Resistance is usually due to a thymidine kinase deficiency, which leads to excessive proliferation of the virus in the host organism. Sometimes reduced sensitivity to acyclovir due to the emergence of strains with impaired viral thymidine kinase or DNA polymerase structure. The virulence of the virus species resembles that of his wild strain.
Pharmacokinetics General: After oral administration valaciclovir is well absorbed from the gastrointestinal tract and rapidly and almost completely transformed into aciclovir and valine. This conversion is catalyzed by the enzyme valatsikpovirgidralazoy isolated from human liver. After receiving a single dose valatsikpovira 250-2000 mg mean peak concentration of acyclovir in plasma in healthy volunteers with normal renal function was 10-37 mol (2,2-8.3 g / ml), and the median time to reach this concentration 1.2 hours. Valatsikpovira When receiving a dose of 1000 mg of acyclovir bioavailability is 54% and is independent of food intake. Peak plasma concentration valatsikpovira in only 4% of the concentration of acyclovir, the median time to achieve it – 30 – 100 minutes post-dose, 3 hours peak concentration level remains the same or decreases. Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration. Degree valatsikpovira binding to plasma proteins is very low (only 15%). In patients with normal renal function, the half-life of acyclovir after administration of valacyclovir plasma is about 3 hours, and in patients with end-stage renal failure average half-life of about 14 hours.Valaciclovir is excreted in the urine mainly as acyclovir (more than 80% of the dose) and metabolite acyclovir 9 karboksimetoksimetilguanina, unaltered eliminated less than 1% of the formulation. Patient characteristics: The pharmacokinetics of valaciclovir and acyclovir largely impaired in patients infected with viruses PIP EOI. in late pregnancy daily steady rate “area under curve” (area under the curve ratios plasma concentration / time) after administration of 1000 mg valaciclovir was greater than about 2 times, than that when taking acyclovir at a dose of 1200 mg per day. Admission trenbolone enanthate for sale 1000 mg or 2000 mg does not violate the disposition and pharmacokinetic parameters of valaciclovir in HIV-infected patients compared to healthy individuals. In recipients of organ transplants, receiving valaciclovir 2000 mg 4 times daily, peak concentration of acyclovir is equal to or superior to that of in healthy volunteers receiving the same dose, and the daily performance “area under the curve” they are much higher.
- Treatment of herpes zoster (shingles). trenbolone enanthate for sale accelerates the disappearance of pain, reduces its duration and the percentage of patients with pain caused by herpes zoster, including acute and post-herpetic neuralgia.
- Treatment of infections of the skin and mucous membranes caused by HSV, including first identified and recurrent genital herpes.
- Treatment of herpes labialis (lip fever).
- trenbolone enanthate for sale is able to prevent the formation of lesions, if taken at the first symptoms of herpes simplex recurrence.
- Prevention (suppression) of recurrences of infections of the skin and mucous membranes caused by HSV, including genital herpes.
- trenbolone enanthate for sale can reduce genital herpes infection of the healthy partner, if taken as suppressive therapy in combination with safer sex.
- Prophylaxis of cytomegalovirus (CMV) infections occurring in organ transplantation. Prophylactic treatment with trenbolone enanthate for sale reduces the severity of CMV infection of acute transplant rejection (in patients with kidney transplants), opportunistic infections and other herpes infections (HSV, VZV).
trenbolone enanthate for sale is contraindicated in patients with hypersensitivity to valatsikpoviru, atsikpoviru and any auxiliary ingredients in the drug.
It should be used with caution in symptomatic forms of HIV.
Pregnancy and lactation Teratogenicity: Valaciclovir is not teratogenic in rats and vozdeystiya rabbits. Valaciclovir is almost completely metabolised to aciclovir education. Subcutaneous administration of aciclovir in standard tests for teratogenicity caused no teratogenic effects in rats and rabbits. In additional studies in rats of fetal development were found by subcutaneous administration of the drug in doses which induced an increase in the plasma concentration of acyclovir to 100 ug / mL and the toxic effects in the mother. Fertility: Orally valacyclovir did not induce fertility disorders in male and female rats .pregnancy: the use of trenbolone enanthate for sale in pregnancy is insufficient data. trenbolone enanthate for sale should be used during pregnancy only if the potential benefit outweighs the potential risk. The data records of the outcome of pregnancy in women who took trenbolone enanthate for sale or Zovirax (Acyclovir is an active metabolite of valaciclovir), showed no increase in the number of birth defects in their children compared with the general population. Since the register included a small number of women taking valacyclovir during pregnancy, the reliable and specific conclusions about the safety of valaciclovir in pregnancy can not be done. Lactation: acyclovir, the main metabolite of valaciclovir, is excreted in breast milk. After assigning the valaciclovir 500 mg of acyclovir into the maximum concentration (Cmax) in breast milk in 0,5-2,3 times (an average 1.4 times) higher than the corresponding concentration of acyclovir in maternal plasma. The ratio of AUC of acyclovir present in breast milk, to the mother of acyclovir plasma AUC ranged from 1.4 to 2.6 (mean 2.2).The average value of the concentration of acyclovir in breast milk was 2.24 micrograms / ml (9.95 mkgM). When receiving mother valaciclovir 500 mg 2 times a day child undergo a similar treatment of acyclovir as when taking it orally in a dosage of about 0.61 mg / kg / day. The half-life of acyclovir from breast milk is the same as from the blood plasma. Valacyclovir in unchanged form was not detected in maternal plasma, breast milk, urine, or a child. trenbolone enanthate for sale should be used with caution in nursing women. However / in a Zovirax 30 mg / kg / day is used to treat neonatal diseases caused by herpes simplex virus.
Dosage and application Treatment of herpes zoster Adults trenbolone enanthate for sale administered in a dose of 1000 mg 3 times daily for 7 days. Treatment of infections caused by HSV Adults trenbolone enanthate for sale administered in a dose of 500 mg 2 times a day. In the case of relapse, treatment should continue for 3 to 5 days . In more severe cases, the primary treatment should be started as early as possible, and its duration should be increased from 5 to 10 days. In recurrent HSV is considered an ideal appointment of trenbolone enanthate for sale in the prodromal period or immediately upon appearance of the first symptoms of the disease. As an alternative for the treatment of herpes labialis (lip fever) effectively appointment trenbolone enanthate for sale dose of 2 g twice a day for 1. The second dose should be taken approximately 12 hours later (but not earlier than 6 hours) after the first dose. By using such dosing regimen duration of treatment should not exceed one day as it was shown to provide no additional clinical benefit. Therapy should be initiated with the appearance of the earliest symptoms of fever lip (ie, tingling, itching, burning). Prevention (suppression) of recurrences of infections caused by HSV Adult patients with preserved immune trenbolone enanthate for sale is appointed at a dose of 500 mg once a day. In patients with very frequent recurrences (10 or more per year) an additional effect can be achieved by assigning trenbolone enanthate for sale in a daily dose of 500 mg, divided into two doses (250 mg, 2 times a day). for adult patients with immunodeficiencies recommended dose trenbolone enanthate for sale 500 mg two times a day. Duration of treatment is 4-12 months. Infection prevention genital herpes healthy partner. The infected heterosexual adults with preserved immunity and the number of exacerbations of up to 9 per year, should take trenbolone enanthate for sale 500 mg 1 time a day for a year or more every day at regular sexuality, with no regular sexual intercourse receiving trenbolone enanthate for sale should be started 3 days prior to the alleged sexual contact. Data on the prevention of infections in other patient populations does not exist. prevention of CMV infection doses for adults and adolescents (from 12 years) recommended to appoint trenbolone enanthate for sale dose of 2 g 4 times a day, as soon as possible after transplantation. The dose should be reduced according to creatinine clearance. The duration of treatment is 90 days, but in patients with a high risk, treatment may be longer. Doses in renal failure: treatment of herpes zoster and infections caused by HSV, prevention (suppression) and the reduction of infection of a healthy life: The dose of trenbolone enanthate for sale is recommended to reduce in patients with a significant decrease in renal function (see. dose of renal failure in the table).
|Therapeutic indications||Creatinine clearance ml / min||The dose of trenbolone enanthate for sale|
for at least 15
|1 g of 2 times daily
1g once a day 1
|Herpes simplex (treatment)||less than 15||500 mg 1 time per day|
|Herpes labialis (treatment) (2 g in 2 divided doses for 1 day)||31-49
less than 15
|1g twice a day for 1
to 500 mg twice a day for 1
to 500 mg once
|Herpes simplex prevention (suppression):
– patients with preserved immune
– Patients with reduced immunity
|less than 15
less than 15
|250 mg 1 time per day
to 500 mg 1 time per day
|Reduction of infection with genital herpes||less than 15||250 mg 1 time per day|
Patients who are on hemodialysis, it is recommended to use trenbolone enanthate for sale immediately after hemodialysis in the same dose as patients with creatinine clearance less than 15 ml / min. Prevention of CMV: trenbolone enanthate for sale destination mode in patients with impaired renal function should be installed in accordance with the table of the below.
|Creatinine clearance ml / min||The dose of trenbolone enanthate for sale|
|75 or more||2 g 4 times a day|
|from 50 to less than 75||1.5 g 4 times a day|
|from 25 to less than 50||1.5 grams 3 times per day|
|from 10 to less than 25||1.5 g of 2 times a day|
|less than 10 or dialysis *||1.5 g 1 day|
In patients on hemodialysis, the trenbolone enanthate for sale should be administered after hemodialysis.
It is necessary often to determine creatinine clearance, especially during periods when renal function is changing rapidly eg immediately after transplantation or engraftment, and the trenbolone enanthate for sale dose is adjusted according to the performance of clearance creatinine. The dose of trenbolone enanthate for sale with abnormal liver function in patients with mild to moderately severe cirrhosis of the liver (hepatic synthetic function maintained) trenbolone enanthate for sale dose adjustment is required. Pharmacokinetic data in patients with severe hepatic cirrhosis (in violation of the synthetic function of the liver and the presence of shunts between the portal system and general vascular bed) also do not indicate a need to adjust the dose of trenbolone enanthate for sale, however, the experience of its clinical applications in this disease is limited. Doses in children No data the use of trenbolone enanthate for sale in children. The doses in elderly patients a dose adjustment is not required, except for a significant renal dysfunction. It is necessary to maintain an adequate fluid and electrolyte Ballance.
Adverse reactions are listed below according to the classification by major systems and organs and occurrence frequency.
Used frequency data: Very often: ≥ 1 on 10 Most: ≥ 1 in 100 and <1 to 10; Uncommon: ≥ 1 in 1,000 or < 1 100 rare: ≥ 1 in 10,000 and <1 per 1,000 Very rare: <1 in 10,000 disorders of the nervous systemCommon: headache. Disorders of the gastrointestinal tract Common: nausea. These post-marketing studies Disorders of blood and lymph system Very rare: leucopenia, thrombocytopenia. Basically, leukopenia was observed in patients with reduced immunity. Violations by the immune system Very rare: anaphylaxis. Mental disorders and disorders of the nervous system Rare: dizziness, confusion, hallucinations, decreased mental abilities. Very rare: agitation, tremor, ataxia , dysarthria, psychotic symptoms, convulsions, encephalopathy, coma. The above symptoms are reversible and usually seen in patients with impaired renal function or in the background of other predisposing conditions. Patients with organ transplant, receiving high doses (8 g daily) of trenbolone enanthate for sale for prophylaxis of CMV infection, neurological reactions occur more often than when receiving lower doses. Violations of the respiratory organs of thoracic and mediastinal disorders Uncommon: dyspnoea Disorders of the gastrointestinal -kishechnogo tract rare: abdominal discomfort, vomiting, diarrhea disorders of the liver and bile ducts Very rare: reversible disturbances of liver function tests, which are sometimes regarded as manifestations of hepatitis. violations of the skin and subcutaneous tissue Uncommon: rash, including photosensitivity manifestations. rare: . pruritus Very rare: urticaria, angioneurotic edema.violations of the kidney and urinary tract rare: renal dysfunction. Very rare: acute renal failure, renal colic. (Renal colic may be associated with renal impairment.). Others: In patients with severely impaired immune system, especially in patients with an advanced stage AIDS receiving high doses of valaciclovir (8 g daily) for a long period of time, the cases of renal failure was observed , microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). These complications have been observed in patients with the same disease but not receiving valacyclovir.
Overdose Symptoms and signs: data on overdose of trenbolone enanthate for sale are not sufficient. Single administration of an overdose to 20 g of acyclovir, which partly is absorbed from the gastrointestinal tract, is not accompanied by toxic effects of the drug. Ingestion within a few days of ultrahigh doses of acyclovir was associated with gastrointestinal (nausea and vomiting) and neurological symptoms (headache and confusion). Overdose with intravenous acyclovir accompanied by an increase in serum creatinine levels and the subsequent development of renal failure, and the neurological complications include confusion, hallucinations, agitation, seizures and coma. Management: Patients should be monitored closely to detect signs of toxic effects. Haemodialysis significantly enhances the removal of aciclovir from the blood and can be considered the treatment of choice in the management of patients with an overdose of trenbolone enanthate for sale.
Interaction with other drugs
Clinically significant interactions have not been established. Acyclovir is eliminated in the urine primarily as unchanged active in secreting renal tubule. Following the appointment of 1g. trenbolone enanthate for sale, cimetidine and probenecid to block tubular secretion, increase the AUC of aciclovir and reduce its renal clearance. However, this dose of trenbolone enanthate for sale does not require any correction due to the wide therapeutic index of aciclovir. Care must be taken in the case of simultaneous application trenbolone enanthate for sale higher doses (4 g daily) and drugs that compete with acyclovir for elimination pathway, since there is a potential threat to increase the plasma level of one or both drugs or their metabolites. It was observed increase in AUC of acyclovir and the inactive metabolite of mycophenolate mofetil, an immunosuppressive drug used in transplantation, while the use of these drugs. It should also be taken (to observe the change of renal function) trenbolone enanthate for sale when combined at higher doses (4 g. Per day or more) with drugs that affect the other kidney (e.g., cyclosporine, tacrolimus).
Cautions degree of hydration of the body: in patients at risk of dehydration, especially in elderly patients, it is necessary to provide adequate fluid replacement. Use in renal failure: trenbolone enanthate for sale dose should be adjusted depending on the degree of renal dysfunction. Patients with renal impairment are at increased risk of neurological complications. The use of higher doses of trenbolone enanthate for sale in hepatic failure and liver transplantation: no data on the use of trenbolone enanthate for sale in higher doses (4g or more per day.) In patients with liver disease, so high dose trenbolone enanthate for sale they should be used with caution. Special studies on the effect of Valtraksa not provola liver transplant. However, it has been shown that prophylactic atseklavira in high doses reduces CMV infection. Use in genital herpes: suppressive therapy trenbolone enanthate for sale reduces the risk of transmission of genital herpes, but do not eliminate it completely and does not lead to a complete cure. trenbolone enanthate for sale therapy is recommended in combination with safer sex.