Nikavir

General characteristics. Structure:

Active agent: фосфазид – 200 mg or 400 mg.

Excipients: calcium the carbonate (besieged) cellulose microcrystallic, silicon dioxide colloid (aerosil), calcium stearate.

Pharmacological properties:

Pharmacodynamics. Active agent фосфазид belongs to the class of inhibitors of the return transcriptase (revertaza) of retroviruses, being the modified analog of a natural nucleoside of thymidine. Fosfazid, having got into the infected cell, it is twice phosphorylated to an active metabolite – triphosphate of azidothymidine which is built in instead of thymidine triphosphate the chain of antiviral DNA synthesized revertazy that leads to revertaza inhibition, break of a chain of DNA and a stop of reproduction of virus particles. The therapeutic effect of drug on decrease in concentration of HIV in the patient's blood is also based on this mechanism. Also drug inhibits replication of some other retroviruses of mammals, for example, of a hepatitis B virus. 

Pharmacokinetics. Fosfazid is well soaked up from digestive tract. Time of full absorption makes 3-3,5 h; biological half-life – 3-4 h; the maximum concentration of a fosfazid in a blood plasma – 19-22 mkg/ml is reached in 4-5 h. Bioavailability of tablets makes about 20% of internal introduction. Relative bioavailability of a fosfazid makes 83,7% to a zidovudine. Fosfazid gets through a blood-brain barrier and it is found in cerebrospinal fluid in the concentration making 15-64% of an initial dose. Active agent well gets through a placenta owing to what its concentration in blood of an umbilical cord is comparable from that mother in blood. Metabolism of a fosfazid happens in a liver to formation of a glucuronide which is brought out of an organism by kidneys with urine.

Indications to use:

HIV infection. Drug is used at monotherapy or in a combination with other anti-retrovirus drugs at HIV-positive patients in a stage of secondary diseases (a stage 3A, 3B, 3B on the Pokrovsk V. I. classification 1989), in a stage of an acute infection (2A) and at primary manifestations (2B, 2V) at decrease in level of CD4T-lymphocytes less than 400-500 in 1 mm3 and increase in the HIV RNA level more than 20 thousand copies on 1 ml (when determining by RT PCR method), and also in an incubation stage (a stage 1).

Drug can be used at the emergency prevention of HIV infection in case of professional risk of infection with the contaminated HIV-positive biological material at pricks, cuts, hit on mucous membranes.

The acute hepatitis V. Preparat is appointed the patient in an easy and medium-weight form (the icteric period).

Route of administration and doses:

HIV infection. Accept inside in tablets 200 mg. Daily doses at HIV infection:

- adults: 600-1200 mg a day in 2 receptions;

- children up to 13 years: 10 mg on 1 kg of body weight in 2-3 receptions;

- teenagers are more senior than 13 years: on 200 mg 3 times a day.

It is recommended to accept drug before food and to wash down with a glass of water. At damages of the central nervous system a retrovirus drug appoint in a daily dose 1200 mg for adults and 20 mg to 1 kg of body weight – to children. At bad portability of drug the daily dose can be lowered to 400 mg a day at adults and to 5 mg on 1 kg of body weight at children.

Course of treatment. Drug is appointed to long, almost unlimited term, if necessary the course can be interrupted, but duration it has to make not less than 12 weeks with a break between courses – no more than 12 weeks.

Treatment by drug (monotherapy) is carried out according to the continuous scheme at patients with acute HIV infection (a stage 2A) for clinical manifestations (plus 1 month later, but not less than 3 months); in stages 3A and 3B in a phase of lack of clinical manifestations, also as well as in stages of primary manifestations (2B and 2V), drug appoint 200 at number of CD4T-lymphocytes. CD4.500 courses for 12 weeks with a break in 12 weeks.

For prevention of professional infection of HIV it is recommended as soon as possible, but not later than in 72 hours after possible infection to begin administration of drug on 600 mg 2 times a day within 4 weeks.

The acute hepatitis V. Preparat is appointed by the adult on 400 mg by 2 times a day within 20 days. It is recommended to begin to accept drug no later than 7 days from the beginning of jaundice. Data on use of drug for children are absent.

Features of use:

Usually drug is well transferred both by adults, and children. Fosfazid – low-toxic. Its toxicity is 5-6 times lower, than a zidovudine. Estimating portability of drug, it is necessary to consider that the specified side effects and other symptoms and syndromes can be manifestations not only therapies, but also the HIV infection and associated diseases.

At manifestation of some undesirable phenomena at early stages of administration of drug it is not necessary to cancel it, it is recommended to continue therapy.

The irregularity of administration of drug by the patient (disturbance of the scheme of treatment) can lead to development of resistance (stability) of a retrovirus to it that will cause decrease in efficiency of the carried-out therapy and need of replacement of drug.

In order to avoid complications drug is used under control of the doctor.

Therapy by drug does not reduce risk of transfer of HIV to other people at sexual contacts or at hemotransfusion.

Side effects:

In rare instances at the beginning of a course of treatment – nausea, a headache, weight in the epigastriums, diarrhea disappearing within several next days of treatment. In isolated cases a granulocytopenia and anemia, however, their communication with therapy by drug Nikavir. it was not proved. If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Drug can be used in combination with other anti-retrovirus drugs in the combined schemes of treatment, however combined use of drug Nikavir with a zidovudine, stavudiny leads to mutual decrease of the activity concerning HIV.

Combined use with interferon, didanoziny, lamivudiny, foskarnety leads to mutual increase in activity concerning HIV.

Combined use with doxorubicine, interferon, amfoteritsinom-V, co-trimoxazole, vinblastine, Vincristinum, gantsikloviry, dapsone, Sulfadiazinum and other streptocides can lead to mutual strengthening of a miyelotoksichnost therefore additional control of concentration of hemoglobin and granulocytes is required.

Contraindications:

Hypersensitivity to a fosfazid or to any of drug excipients. Before administration of drug surely consult with the doctor.

At hepatitis B at children it is not applied.

With care. A relative contraindication to purpose of drug is the expressed nausea, vomiting, decrease in hemoglobin is lower than 50 g/l, increase in activity of aminotransferases and creatinine in blood serum more than by 5 times of rather upper bound of norm, decrease in quantity of neutrophils to 500 in мкл, decrease in quantity of thrombocytes less than 25 thousand in мкл.

Overdose:

In case of intoxication drug (still it was not noted) the hemodialysis and peritoneal dialysis significantly strengthen removal of a glucuronic metabolite of a fosfazid.

Storage conditions:

In the dry place protected from light at a temperature not above 25 °C. To protect from children.

Issue conditions:

According to the recipe

Packaging:

10 tablets on 200 mg or on 400 mg in a blister strip packaging (blister) from plenki-PVH and a foil; on 2 blisters (20 tablets on 200 mg) or on 6 blisters (60 tablets on 400 mg) with the application instruction in a pack from a cardboard. On 20, 30, 60 tablets in banks polymeric, corked by a cover. Bank with the application instruction in a pack from a cardboard.