Valaciclovir pills 500mg №50

Pharmacological group:

antivirals (except for HIV) / nucleoside analog.

Pharmachologic effect:

antiherpetic, antiviral.

Pharmacological properties

Valacyclovir is a prodrug that in the body is almost completely and quickly converted to Acyclovir, which acquires specific activity after phosphorylation processes. Acyclovir is a structural analogue of purine nucleosides (normal components of DNA), which blocks the multiplication of viruses through interaction with its DNA polymerase. Antiherpetic selective activity is possible due to the similarity with Herpes simplex thymidine kinase, Epstein-Barr virus, Varicella zoster. With the participation of thymidine kinase, the virus is first transformed into acyclovirmonophosphate, then, under the action of guanylate kinase, human cells are transformed into acyclovir diphosphate and then into acyclovir triphosphate (which is the active form). Triphosphate prevents the replication of the DNA of the virus due to the fact that it competitively inhibits the DNA polymerase of the virus and inhibits the lengthening of the DNA chain. In vitro is active against Epstein-Barr viruses, Varicella zoster, Herpes simplex type 1 and 2, human herpes virus type 6, cytomegalovirus. The resistance of Varicela zoster and Herpes simplex strains is formed due to hidden changes in DNA polymerase or thymidine kinase or due to phenotypic deficiency of virus thymidine kinase; such resistance in patients with a normal immune system is very rare,significantly more often with various immunodeficiencies (for patients who receive Chemotherapy for cancer, for HIV infection, and others). Valacyclovir is rapidly absorbed in the gastrointestinal tract after ingestion and as a result of metabolism in the intestine and the liver is converted into acyclovir and L-valine almost completely (99%). The pharmacokinetics of acyclovir and valaciclovir after ingestion have been studied in 14 studies in healthy adult volunteers. When taking 1000 mg of valaciclovir hydrochloride, the absolute bioavailability of acyclovir was 54.5 ± 9.1% and did not depend on food intake. Pharmacokinetic parameters when using different doses of the drug dose is not proportional. For example, after taking valaciclovir hydrochloride (once) in doses of 1000, 750, 500, 250, 100 mg, the maximum concentration of acyclovir was 5.65; 4.17; 3.28; 2.15; 0.83; mcg / ml, AUC -19.52; 14.11; 11.59; 5.76; 2.28 h • mkg / ml, respectively. After taking valacyclovir hydrochloride (many times, 4 times a day for 11 days) in doses of 1000, 500, 250 mg, the maximum concentration is 4.96; 3.69; 2.11 mcg / ml and AUC - 15,70; 9.88; 5.66 h • mcg / ml, respectively. Plasma concentration of unchanged valaciclovir is very low, less than 0.5 μg / ml at all doses studied, and after 3 hours valaciclovir is not detected in plasma; Valaciclovir binds to proteins 13.5-17.9%. Acyclovir undergoes biotransformation under the influence of aldehyde and alcohol dehydrogenase, aldehyde oxidase with the formation of inactive metabolites. The metabolism of acyclovir / valaciclovir with cytochrome P450 enzymes is not related.The half-life of valaciclovir is less than half an hour, and acyclovir after using valacyclovir hydrochloride 2.5-3.3 hours (in healthy volunteers), in the elderly (65 years-83 years) - 3.3-3.7 hours, in patients with renal insufficiency of time increases. Valaciclovir is excreted by 45.6% in urine and 47.12% in feces for 96 hours. Renal clearance is 255 ml / min. Of the total amount of valacyclovir, which is excreted by the kidneys, 80-90% is excreted as acyclovir. Less than 1% of Valaciclovir is unchanged. After re-use of valaciclovir in patients with normal kidney function, acyclovir does not accumulate. In patients with liver disease of moderate or severe severity, the rate of conversion of valacyclovir to acyclovir decreases, the half-life does not change. In patients with HIV infection, the pharmacological parameters of valaciclovir did not differ from healthy volunteers. When 400 mg / kg was administered to rats and rabbits (plasma concentrations at such a dose higher than a human one by 10 and 7 times, respectively), valacyclovir did not have a teratogenic effect during organogenesis. He also had no effect on fertility when using 200 mg / kg / day (concentration 6 higher than in humans) in female and male rats.

Indications

Infections of the mucous membranes and skin that are caused by the herpes simplex virus (including genital herpes); shingles; prevention of recurrence of diseases that are caused by the herpes simplex virus.

Dosing and Valaciclovir

Valaciclovir is taken orally, regardless of the meal. Depending on the evidence set dosing mode. Treatment should begin as early as possible, its effectiveness is greater if therapy is started for the first time for 2 days of the onset of symptoms or signs of illness (burning or pain, rash). With shingles for 1 week, 3 times a day for 1000 mg. With simple herpes (including genital recurrent) for 5 - 10 days, 2 times a day, 500 mg. In case of renal insufficiency, the dose is reduced: for herpes zoster, every 12 hours, 1000 mg at Cl creatinine 30–49 ml / min or once a day, if Cl creatinine 10–29 ml / min, 500 mg once a day, if Cl creatinine less than 10 ml / min; for simple herpes (including genital) - 500 mg every 12 hours with Cl creatinine 30–49 ml / min or 1 time per day with Cl creatinine less than 30 ml / min; if hemodialysis is performed, then the drug should be taken after it.
When skipping the next reception valaciclovir do it when you remember, the next reception to make after a set time from the last use.
Use with great care in all conditions that are accompanied by immunodeficiency. During clinical trials with hemolytic uremic syndrome and / or thrombocytopenic purpura, and in some cases fatal, in patients with severe HIV infection, after high kidney or bone marrow transplantation.With caution used for violations of the kidneys. In patients with kidney disease who received high doses of the drug, there were cases of disorders of the central nervous system and acute renal failure. Older people with valaciclovir therapy need to increase the amount of fluid they drink. When treating genital herpes, sexual contact should be avoided.

Contraindications

Hypersensitivity (including acyclovir), kidney transplantation, bone marrow transplantation.

Restrictions on the use of

Renal impairment, age up to 12 years (efficacy and safety of use are not defined), expressed forms of HIV infection.

Use during pregnancy and lactation

In pregnancy, valaciclovir may be used if the expected effects of treatment exceed the possible risks to the fetus (no safety studies have been carried out in pregnant women). Data on the outcome of pregnancy in women who took acyclovir in the first trimester of pregnancy (acyclovir is the active metabolite of valacyclovir) did not indicate an increase in the number of congenital malformations in children when compared with the general population. Since a small number of women were included in such observations, it is impossible to make definite and reliable conclusions about the safety of taking valaciclovir during pregnancy. Acyclovir, being the main metabolite of valacyclovir, is excreted in breast milk.Valaciclovir itself in unchanged form of breast milk is not detected. Valaciclovir should be applied to lactating women with extreme caution and only when necessary.

Side effects of valacyclovir

Digestive System: nausea, pain and discomfort in the stomach, diarrhea, vomiting, anorexia, a passing increase in liver function tests;
nervous system: dizziness, fatigue, headache, tremor, hallucinations, depression, confusion, delirium, encephalopathy, coma (in the event of renal impairment);
Allergic reactions: pruritus, urticaria, rash, anaphylaxis, angioedema; others: dyspnea, alopecia, hypertension, arthralgia, dysmenorrhea, photosensitivity, tachycardia, thrombocytopenia, renal failure.

The interaction of valacyclovir with other substances

In patients with normal renal function, clinically significant interactions have not been established. Probenecid and cimetidine (together or separately) after a single dose of 1000 mg of valaciclovir increase the AUC and maximum concentration and reduce the renal clearance of acyclovir. The pharmacokinetics of valaciclovir do not change when used together with Magnesium or aluminum containing antacids, Digoxin, thiazide diuretics. Nephrotoxic drugs increase the possibility of developing disorders of the central nervous system and renal failure.

Overdose

In case of overdose, the deposition of acyclovir in the tubules of the kidneys occurs. Hemodialysis is necessary (for anuria and acute renal failure).