Nevirpin

General characteristics. Structure:

Active ingredient: 100,0 mg or 200,0 mg of not Virapinum.

The antiviral medicine used for prevention and treatment of HIV infections.

Pharmacological properties:

Pharmacodynamics. Antiviral means. Is not nucleotide inhibitor of the return VICh-1 transcriptase. Directly connects to the return transcriptase and blocks activity of a RNA-dependent and DNA-dependent polymerase, causing destruction of the catalytic site of enzyme.

On the action mechanism not Virapinum does not compete with matrix or nukleozidny triphosphates, does not inhibit the return VICh-2 transcriptase and a DNA polymerase (α, β, γ or δ) the person.

In a combination with a zidovudine / диданозином reduces quantity of viruses in serum and increases quantity of CD4+ of cells.

Pharmacokinetics. After intake not Virapinum is quickly absorbed (more than 90%) at healthy volunteers and VICh-1 of the infected adult patients. After a single dose in a dose of 200 mg of Cmax in a blood plasma it was reached in 4 h and made 2±0.4 mkg/ml (7.5 µmol). At course use linear increase in Cmax of not Virapinum in plasma in the range of doses of 200-400 mg/days was observed.

Meal, antacids and other medicines containing an alkaline buffer component (for example, диданозин), does not exert impact on absorption of not Virapinum.

Not Virapinum is lipophilic substance and is practically not ionized at physiological value рН. Later in/in introductions by healthy adult Vd made 1.21±0.09 l/kg that confirms good distribution of not Virapinum in tissues of the person. Concentration of not Virapinum in cerebrospinal fluid makes 45% (±5%) from concentration in plasma.

At concentration in plasma of 1-10 mkg/ml contacts proteins of plasma for 60%.

Cssmin was reached at a dose of 400 mg/days and made 4.5±1.9 mkg/ml.

It is metabolized with the participation of microsomal enzymes of a liver of system of P450 cytochrome, preferential by CYP3A isoenzymes with formation of several hydroxylated metabolites.

It is removed by kidneys (about 80%) in the form of the metabolites conjugated with glucuronic acid, in insignificant quantities - in not changed look.

Not Virapinum is the inductor of microsomal enzymes of the CYP system.

At intake on 200 mg of 2 times/days during 2-4 weeks the seeming clearance of not Virapinum increases by 1.5-2 times in comparison with a single dose in the same dose, T1/2 in a terminal phase decreases from 45 h at a single dose to 25-30 h at course use. Change of these parameters is connected with a pharmacokinetic self-induction.

Pharmacokinetic parameters of not Virapinum do not change depending on age at patients of 19-68 years or an ethnic origin. Vd at women is slightly higher, than at men, but the essential distinctions of concentration of not Virapinum connected with a floor is not revealed.

At the children infected with VICh-1, AUC and Cmax raised in proportion to increase in a dose. After the end of absorption concentration of not Virapinum in a blood plasma linearly decreased eventually.

The clearance of not Virapinum in terms of body weight reached the maximum values at patients aged from 1 up to 2 years, then decreased in proportion to age. The clearance of not Virapinum at patients aged up to 8 years was approximately twice lower, than at adult patients. T1/2 after achievement of Css averaged 25.9±9.6 h (for the VICh-1 group of the infected patients with average age of 11 months).

At prolonged use of T1/2 in a terminal phase changes depending on age and makes at children aged from 2 months till 1 year - 32 h, 1-4 years - 21 h, 4-8 years - 18 h, 8 years - 28 h are more senior.

Indications to use:

Treatment of the adults and children infected with VICh-1 (in a combination at least with 2 anti-retrovirus drugs).

Prevention of the transmission of infection caused by VICh-1 from mother to the newborn (at the women who were not receiving anti-retrovirus treatment at the time of delivery).

Route of administration and doses:

At intake by adult - 200 mg of 1 times/days daily during the first 14 days (the introduction period), then increase a dose to 200 mg of 2 times/days daily (in a combination at least with 2 anti-retrovirus drugs).

The recommended doses to children aged from 2 months up to 8 years - 4 mg/kg of 1 times/days during the first 14 days, then on 7 mg/kg/days of 2 times/days; to children at the age of 8 years is also more senior - 4 mg/kg of 1 times/days during the first 14 days, then on 4 mg/kg of 2 times/days.

The maximum daily dose for patients of any age makes 400 mg.

Patients who during the 14-day introduction period of use of not Virapinum had a rash should not carry out increase in a dose up to total disappearance of rash.

For prevention of transfer of HIV from mother to the child the single dose at the time of delivery in a dose of 200 mg with the subsequent single peroral introduction is recommended to the newborn during 72 h after the birth in a dose of 2 mg/kg.

At moderate changes of indicators of a functional condition of a liver (except for GGT) reception of not Virapinum should be interrupted until these indicators are not returned to initial level, then not Virapinum apply 200 mg/days in a dose. The subsequent increase in a dose (on 200 mg of 2 times/days) it is necessary to make carefully after the long period observations of the patient. At repeated emergence of changes of indicators of a liver treatment should be stopped finally.

At the patients who were not receiving not Virapinum more than 7 days, treatment is resumed, since a dose of 200 mg/days within 14 days, then increase a dose to 200 mg of 2 times/days.

Features of use:

Adequate and strictly controlled clinical trials of safety of use of not Virapinum at pregnancy were not conducted. It is established that not Virapinum easily gets through a placental barrier. Use at pregnancy is possible only if the estimated advantage for mother exceeds potential risk for a fruit.

Not Virapinum is allocated with breast milk. In need of use in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Efficiency and safety of use of not Virapinum for prevention of a VICh-1 broadcast from mother to the child at intake is shown at the time of delivery of a single dose of 200 mg and a single dose of 2 mg/kg for the newborn during 72 h after the birth.

During treatment use of barrier methods of contraception is recommended.

In pilot studies teratogenic action of not Virapinum is not revealed. Decrease in fertility at females of rats at introduction of not Virapinum in the doses providing intake of active agent in a system blood stream, defined on the basis of AUC which is approximately equivalent that at use of not Virapinum in the recommended clinical doses is shown.

Use at abnormal liver functions. With care to apply at patients with abnormal liver functions. During treatment it is necessary to carry out dynamic control of a functional condition of a liver, especially within the first 6 months. At increase in ALT and nuclear Heating Plant values it is necessary to control functions of a liver more often twice.

If ALT and nuclear Heating Plant values exceed the upper bound of norm more than by 5 times, not Virapinum should be cancelled immediately. In case of decrease in values of enzymes perhaps repeated use which begin with the 14-day introduction period in the mode 200 mg/days with the subsequent increase up to 400 mg/days. At repeated fast negative changings of indicators of function of a liver not Virapinum should be cancelled.

Use at renal failures. With care to apply at patients with renal failures. Use of not Virapinum in a dose of 200 mg in addition after each procedure of dialysis is recommended to the patients with renal failures who are on dialysis. It allows to compensate influence of dialysis on clearance of not Virapinum. With KK20 dose adjustment is not required to ml/min. from patients.

Use for children. The recommended doses to children aged from 2 months up to 8 years - 4 mg/kg of 1 times/days during the first 14 days, then on 7 mg/kg/days of 2 times/days; to children at the age of 8 years is also more senior - 4 mg/kg of 1 times/days during the first 14 days, then on 4 mg/kg of 2 times/days.

For prevention of transfer of HIV from mother to the child the single dose at the time of delivery in a dose of 200 mg with the subsequent single peroral introduction is recommended to the newborn during 72 h after the birth in a dose of 2 mg/kg.

In the first 8 weeks of treatment special control of a condition of the patient for the purpose of bystry identification of possible heavy and life-threatening skin reactions (including Stephens-Johnson's syndrome, a toxic epidermal necrolysis), hepatitis or a renal failure is required.

Reception of not Virapinum should be interrupted if at patients emergence of the expressed rash or rash in combination with fever, formation of vesicles, damages of an oral cavity, conjunctivitis, a face edema, a mialgiya or an arthralgia, a febricula is noted, and also at the expressed changes of hepatic tests, eosinophilias, a granulocytopenia, hepatitis, a renal failure or emergence of signs of dysfunctions of other internals. In such cases not Virapinum is repeatedly not applied.

Disturbance of the mode of dosing during the introduction period increases the frequency of development of skin reactions.

At a reception break more than 7 days repeated use should be begun with the introduction period.

With care to apply at patients with abnormal liver functions or kidneys. Use of not Virapinum in a dose of 200 mg in addition after each procedure of dialysis is recommended to the patients with renal failures who are on dialysis. It allows to compensate influence of dialysis on clearance of not Virapinum. With KK20 dose adjustment is not required to ml/min. from patients.

During treatment it is necessary to carry out dynamic control of a functional condition of a liver, especially within the first 6 months. At increase in ALT and nuclear Heating Plant values it is necessary to control functions of a liver more often twice.

If ALT and nuclear Heating Plant values exceed the upper bound of norm more than by 5 times, not Virapinum should be cancelled immediately. In case of decrease in values of enzymes perhaps repeated use which begin with the 14-day introduction period in the mode 200 mg/days with the subsequent increase up to 400 mg/days. At repeated fast negative changings of indicators of function of a liver not Virapinum should be cancelled.

Asymptomatic increase in GGT is not the indication for cancellation of not Virapinum.

At emergence of clinical and laboratory signs of hepatitis (the moderated or expressed changes of indicators of function of a liver except GGT) not Virapinum is completely cancelled and repeatedly not applied.

The remote effects of not Virapinum are unknown now.

Reception of not Virapinum does not reduce risk of a VICh-1 broadcast at sexual contact.

At simultaneous use of not Virapinum and hormonal contraceptives it is necessary to control efficiency of the last.

Influence on ability to driving of motor transport and to control of mechanisms. In case of drowsiness against the background of treatment, it is recommended to avoid potentially dangerous types of activity.

Side effects:

Dermatological reactions: the makulo-papular erythematic skin rash which sometimes is followed by an itch (it is localized on a trunk, a face or extremities). In most cases rash is noted during the first 28 days.

Allergic reactions: the fever, an arthralgia, a mialgiya, a lymphadenopathy which are followed by one or several of below the listed symptoms are possible: hepatitis, eosinophilia, granulocytopenia, renal failure and symptoms testimonial of damage of other internals; anaphylactic reactions, a Quincke's disease, a small tortoiseshell, Stephens-Johnson's syndrome and a toxic epidermal necrolysis (in rare instances leading to a lethal outcome).

From the alimentary system: often - increase in activity of GGT; are possible - increase in activity of ALT, nuclear heating plant, ShchF and level of the general bilirubin, nausea, vomiting, diarrhea, abdominal pains; in isolated cases - jaundice, heavy hepatotoxic reactions.

From system of a hemopoiesis: a granulocytopenia (is more often at children).

From TsNS: increased fatigue, headache, drowsiness.

Others: fever, mialgiya.

Interaction with other medicines:

At simultaneous use with not Virapinum decrease in concentration in plasma of hormonal contraceptives for intake is possible that causes efficiency reduction.

At simultaneous use of a ketokonazol and not Virapinum decrease in AUC and Cmax of a ketokonazol is noted. Ketokonazol increases concentration of not Virapinum in plasma for 15-28% (simultaneous use is not recommended).

At simultaneous use with Cimetidinum the minimum Css of not Virapinum in plasma was higher, than without Cimetidinum.

Ketokonazol and erythromycin lead to considerable reduction of formation of hydroxylated metabolites of not Virapinum.

Not Virapinum does not exert impact on rifampicin pharmacokinetics. However rifampicin caused considerable decrease in AUC and the minimum concentration of not Virapinum. At simultaneous use of not Virapinum and rifabutin decrease in concentration of not Virapinum is noted. Now there are not enough data for definition of need of change of a dose at simultaneous use of not Virapinum and rifampicin or a rifabutin.

As not Virapinum causes induction of isoenzymes of CYP3A and CYP2B6, at simultaneous use with the drugs which are actively metabolized with the participation of the specified enzymes decrease in concentration in plasma of these drugs is possible.

At the simultaneous use of not Virapinum and drugs containing a St. John's Wort decrease in concentration of not Virapinum below therapeutic level is possible that can lead to loss of virologic efficiency and development of resistance of a virus to not Virapinum (simultaneous use is not recommended).

Owing to features of metabolism of methadone, not Virapinum can reduce concentration of methadone in a blood plasma by strengthening of metabolism of methadone in a liver. At the patients receiving at the same time methadone and not Virapinum cases of development of a narcotic withdrawal are noted (at use of such combination it is necessary to control a condition of the patient and to adjust a methadone dose).

Contraindications:

Hypersensitivity to not Virapinum.

Storage conditions:

To store in places, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

10 pieces - planimetric strip packagings (3) - packs cardboard.
10 pieces - planimetric strip packagings (6) - packs cardboard.
10 pieces - planimetric strip packagings (10) - packs cardboard.
30 pieces - banks polymeric (1) - packs cardboard.
60 pieces - banks polymeric (1) - packs cardboard.
100 pieces - banks polymeric (1) - packs cardboard.
500 pieces - banks polymeric (1) - packs cardboard.