The instruction for use of medicine for experts Улкарил® 200 Улкарил® 400 Улкарил® 800 Trade name Улкарил® 200 Улкарил® 400 Улкарил® 800 International unlicensed name Acyclovir Dosage Form of the Tablet, 200 mg, 400 mg, 800 mg Structure One tablet contains active agent – acyclovir of 200 mg, 400 mg, 800 mg, excipients: lactose, corn starch, magnesium stearate Description Улкарил® 200: tablets of white color, round, with a biconvex surface. Ô½¬áÓ¿½® 400: tablets of white color, round, with a biconvex surface, with risky on one party. Ô½¬áÓ¿½® 800: tablets of white color, oblong, with a biconvex surface, with risky on one party. Pharmacotherapeutic group Antiviral drugs for direct action. Nucleosides and nucleotides the Code of automatic telephone exchange J05AB01 the Pharmacological Pharmacokinetics At properties intake, irrespective of meal, acyclovir is absorbed from digestive tract partially (20%). The maximum concentration in blood plasma is defined in 1.5 – 2 hours. Well gets into bodies and fabrics, concentration of acyclovir in cerebrospinal fluid makes about 50% of its plasma concentration. Acyclovir in insignificant degree contacts proteins of blood plasma (9–33%) therefore medicinal interactions owing to replacement from binding sites with proteins are improbable. The t ½ acyclovirs at intake makes about 4 hours. The most part of drug is removed by kidneys in not changed look. The renal clearance of acyclovir considerably exceeds clearance of creatinine that demonstrates removal of acyclovir by means of not only glomerular filtration, but also canalicular secretion. It is a little metabolized by a liver, the main metabolite of acyclovir is 9-karboksimetoksimetilguanin to which share in urine about 10-15% of the entered drug dose fall. At patients with chronic kidney disease of T1/2 of acyclovir makes, on average, 19.5 h, and when carrying out a hemodialysis average T1/2 of acyclovir – 5.7 h, and concentration of acyclovir in plasma decreases approximately by 60%. Acyclovir gets through hematoencephalic and placentary barriers, is emitted with breast milk. The pharmacodynamics Ulkaril is a synthetic analog of a nucleoside of thymidine. The thymidinekinase of the cells infected with a virus, will actively transform acyclovir through a number of consecutive reactions to mono – di – and acyclovir triphosphate. Triphosphate of acyclovir is built in instead of a deoxyguanosine virus DNA, inhibits a DNA polymerase of the last and suppresses replication process. In herpes acyclovir prevents formation of new elements of rash, reduces the probability of skin dissimination and visceral complications, accelerates formation of crusts. Promotes decrease in pain in a sharp phase of the surrounding herpes. The specificity and very high selectivity of action is also caused by its primary accumulation in the cells affected with a herpes virus. The activity of acyclovir against a herpes simplex virus (type 1) is twice higher, than at Cytarabinum, by 10 times — than at an idoksuridin, by 15 times — than at a trifluorotimidin and by 160 times — than at a vidarabin. It is highly active concerning a virus of a herpes simplex (Herpes simplex (VHS)) of type 1 and 2, a virus of chicken pox and shingles (Varicella zoster (VZV)), a virus Epshtayn-Barra. It is moderately active concerning a cytomegalovirus. Indications – infections of skin and the mucous membranes caused by a herpes simplex virus including primary and recurrent genital herpes – prevention of a recurrence of the infections caused by a herpes simplex virus at patients with the normal immune status and an immunodeficiency – chicken pox – the shingles caused by the Varicella zoster virus – prevention of a Cytomegaloviral infection after bone marrow transplantation the Route of administration and doses by the Adult Lecheniye of the infections caused by a herpes simplex virus the Recommended dose of drug makes 200 mg of 5 times in every day of 4 h, an exception is the period of night sleep. The usual course of treatment makes 5 days, but can be prolonged in heavy primary infections. In case of the expressed immunodeficiency (for example, after bone marrow transplantation) or at disturbance of absorption from intestines the drug dose for intake can be increased up to 400 mg of 5 times a day. Lecheniye needs to begin as soon as possible after developing of an infection. At a recurrence it is already recommended to appoint drug in a prodromal stage or at emergence of the first elements of rash. Prevention of a recurrence of the infections caused by a herpes simplex virus In patients with the normal immune status the recommended dose of drug makes 200 mg 4 times a day (each 6 h), or according to other scheme of therapy — 400 mg 2 times a day (each 12 h). In certain cases effective are lower doses of Ulkaril — 200 mg 3 times a day (each 8 h) or 2 times a day (each 12 h), or the single total daily dose – 800 mg is possible. Drug treatment periodically should be interrupted for 6–12 months for identification of possible changes during a disease. Prevention of the infections caused by a herpes simplex virus In patients with an immunodeficiency the recommended Ulkaril’s dose – 200 mg 4 times a day (each 6 h). In case of the expressed immunodeficiency (for example, after bone marrow transplantation) or at disturbance of absorption from intestines Ulkaril’s dose can be increased up to 400 mg of 5 times a day. Duration of a preventive course of therapy depends on duration of the period of possible risk of infection. Lecheniye of chicken pox and the surrounding herpes the Recommended Ulkaril’s dose makes 800 mg of 5 times a day, the drug is taken by each 4 h, an exception is the period of night sleep. A course of treatment – 7 days. Drug treatment should be begun as soon as possible after the beginning of an infection since the efficiency of treatment depends on it. DetyamLechenie and prevention of the infections caused by a herpes simplex virus at children with an immunodeficiency – of 2 years is also more senior — doses same as for adults – 2 years — a half of a dose for adults are younger. Lecheniye of chicken pox – is more senior than 6 years — 800 mg 4 times a day – from 2 to 6 years — 400 mg 4 times a day – 2 years — 200 mg 4 times a day are younger. More precisely the dose can be defined at the rate of 20 mg/kg of body weight (but no more than 800 mg) 4 times a day. The course of treatment makes 5 days. Is not present recrudesced about prevention of the infections caused by a virus of a herpes simplex and treatment of the surrounding herpes in children with normal indicators of immunity. According to the available limited data, for treatment of children 2 years with the expressed immunodeficiency are more senior it is possible to apply the same doses of Ulkaril, as to treatment of adults. Patients of advanced age At advanced age there is a decrease in clearance of acyclovir in an organism to decrease in clearance of creatinine. Patients of advanced age have to receive enough liquid against the background of reception of high doses of Ulkaril inside, in a renal failure at them it is necessary to resolve an issue of Ulkaril dose decline. Patients with a renal failure At patients with a renal failure the intake of acyclovir inside in the recommended doses for the purpose of treatment and prevention of the infections caused by a herpes simplex virus does not lead to cumulation of drug to the concentration exceeding the established safe levels. However to patients with the profound renal failure (Cl of creatinine & lt, 10 ml/min.) recommend to reduce Ulkaril’s dose to 200 mg 2 times a day (each 12 h). At treatment of chicken pox, the surrounding herpes and also at treatment of patients with the expressed immunodeficiency the recommended Ulkaril’s doses make: – a heavy renal failure (Cl of creatinine & lt, 10 ml/min.) 800 mg 2 times in every day of 12 h – a moderate renal failure (Cl of creatinine of 10-25 ml/min.) of 800 mg 3 times in every day of 8 h. Side effects – a headache, dizziness – increased fatigue, decrease in concentration of attention, a hallucination, drowsiness or insomnia – fervescence – nausea, vomiting, diarrhea, an abdominal pain – a lymphocytopenia, an erythropenia, a leukopenia, is rare – a lymphadenopathy – rash, a photosensitization, urticaria, an itching, fever, is rare — short wind, a Quincke’s disease, an anaphylaxis – increase in concentration in blood of urea, creatinine – reversible increase in level of bilirubin and activity of liver enzymes Seldom – a fast diffusion hair loss (connection with intake of acyclovir is not established) Contraindications – hypersensitivity to acyclovir or other components of drug – dehydration – a renal failure – neurologic disturbances Medicinal interactions Probenetsid blocks canalicular secretion of acyclovir and by that increases concentration of acyclovir in blood plasma, cerebrospinal fluid and its elimination half-life. Acyclovir strengthens effect of nephrotoxic drugs (especially at patients with impaired renal function). Blockers of calcium channels and Cimetidinum increase AUC (the area under a curve “concentration in plasma – time) acyclovir and reduce its renal clearance, however dose adjustment is not required, owing to the wide range of therapeutic doses of acyclovir. The combined use of acyclovir and the mikofenolat of a mofenil, the immunosuppressive drug which is accepted at organ transplantation leads to increase in an indicator of AUC for acyclovir and an inactive metabolite of the mikofenolat of a mofenil. The concomitant use of acyclovir and a zidovudine in HIV infections does not influence kinetics of these drugs. Special instructions At simultaneous use of c nephrotoxic drugs at patients with renal failures and with insufficiency of water loading it is necessary to consider a possibility of development of an acute renal failure, owing to formation of a deposit from acyclovir crystals. At Ulkaril’s use it is necessary to control function of kidneys. Treatment of patients of advanced age should be carried out at sufficient increase in water loading and under observation of the doctor since at this category of patients the elimination half-life of acyclovir increases. If at women with herpes of genitals for the 1st week the state does not improve, it is necessary to perform gynecologic examination. At patients with herpes of genitals the risk of developing cervical cancer therefore it is necessary to carry out the Papanikolau test of 1 times a year for definition of initial changes of a neck of the uterus is increased. At treatment of genital herpes it is necessary to avoid sexual contacts since use of acyclovir does not prevent transfer of a virus to partners. Pregnancy and a lactation women Should be careful at Ulkaril’s appointment during pregnancy and to estimate expected advantage for mother and possible risk for a fruit. Acyclovir gets into breast milk. When breastfeeding children can receive acyclovir in a dose to 0.3 mg/kg/days. Considering this fact, it is necessary to be careful at Ulkaril’s appointment to the feeding women. The feature of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms of Patients should inform on the danger connected with management of transport, service of the mechanical equipment and other potentially dangerous types of activity. Overdose Symptoms: headache, nausea, vomiting, diarrhea, short wind, renal failure, lethargy, spasms, coma. Treatment: there is no specific antidote, symptomatic treatment and supporting. Carrying out dialysis, especially at patients with an acute renal failure is recommended. It is necessary to increase intake of liquid in an organism for prevention of formation of crystals in renal tubules. Form of release and packing of the Tablet of 200 mg, 400 mg, 800 mg. Ô½¬áÓ¿½® 200: in the blister on 25 tablets. 1 blister in a cardboard pack together with the instruction for use. Ô½¬áÓ¿½® 400: in the blister on 5 tablets. 5 blisters in a cardboard pack together with the instruction for use. Ô½¬áÓ¿½® 800: in the blister on 5 tablets. 5 blisters in a cardboard pack together with the instruction for use. To Store storage conditions at a temperature from +15 °C to +30 °C in the dry, protected from light place. To store out of children’s reach! Expiration date Улкарил® 200: 5 years Улкарил® 400: 3 years Улкарил® 800: 2 years not to apply after an expiration date. Prescription status According to the prescription Republic of Kazakhstan JSC Nobel Almatinskaya Pharmatsevticheskaya Fabrika Producer Almaty, Shevchenko St. 162 E.