Telzir

Tselsir is a systemic antiviral drug that belongs to the group of protease inhibitors.

Indications It is

It is used for therapy in HIV infection (complex treatment with ritonavir).

[1], [2], [3], [4], [5]

Release form

The preparation is produced in tablets with a volume of 0.7 g, 60 pieces inside a polyethylene bottle. In the box there is one such bottle.

Oral suspension is also produced, in polyethylene bottles with a capacity of 225 ml. The package contains 1 such bottle, in addition to which is attached a dosage syringe (10 ml volume) and an adapter.

Pharmacodynamics

The drug has an antiviral effect, it is a prodrug of amprenavir.

The element amprenavir is a non-peptidic competitive agent that slows down the activity of the HIV protease. It does not allow the protease of the virus to cleave the polyprotein precursors that are required for viral replication. Amprenavir selectively slows down the replication activity of HIV-1 elements, as well as HIV-2.

[6], [7], [8], [9], [10], [11], [12], [13], [14], [15]

Pharmacokinetics

After oral administration of Telzira, it is almost completely and at high speed hydrolyzed, taking the form of amprenavir, as well as organic phosphate, and then absorbed through the intestinal epithelium.

Absorption.

After repeated re-application of the drug in a dose of 1.4 g (twice per day), amprenavir is absorbed at high speed. Peak values after reaching equilibrium values are 4.82 (within 4.06-5.72) μg / ml, and the time interval required for this is 1.3 (within 0.8-4) hours.

The average geometric level of Cmin is 0.35 (within 0.27-0.46) μg / ml at equilibrium values, and the AUC value is 16.6 (within 13.8-19.6) μg / ml in the interval between applications of drugs. Indicators of AUC are similar in the case of the use of any form of medication on an empty stomach. But the peak plasma level of amprenavir with the use of the suspension is 14% higher than its analogous values when using tablets.

The use, together with tablets of fat-saturated foods, does not affect the pharmacokinetic properties of amprenavir in the plasma.

Consumption of fatty food with a suspension reduces the AUC level by 28%, and the Cmax index by 46% (in comparison with fasting drug use on an empty stomach). Adults should use a suspension on an empty stomach. Children and adolescents should also take it along with food (this is provided by the dosage regimen for this category of patients).

The absolute bioavailability of drugs in humans is not known.

Distribution processes.

The indicator of the apparent distribution volume of amprenavir is approximately 430 liters (6 l / kg, with a weight of 70 kg). The level of large Vd can be explained by the free passage of matter into the tissues of the circulatory system.

The synthesis of amprenavir with protein is about 90%. The substance is synthesized with albumin and the AAG component, but has a higher affinity for the latter.

Exchange processes.

Inside the body, the drug is transformed into amprenavir, which undergoes hepatic metabolism with the help of the CYP3A4 enzyme. Less than 1% of the LS is excreted unchanged through the kidneys.

Excretion.

The half-life of amprenavir is 7 hours. It is excreted in the form of metabolic products through the intestine (approximately 75%), and through the kidneys (approximately 14%).

[16], [17], [18], [19], [20], [21], [22], [23],

Dosing and administration

The drug is used orally (tablets can be taken without taking into account the time of eating, but the suspension is only on an empty stomach).

People who did not use drugs that slow down the activity of the protease are prescribed to take 1.4 grams of drugs twice a day. Also, a regimen of 1.4 g of Tselsir is administered once a day in combination with 0.2 g of ritonavir (once daily). It is possible to take 0.7 g of medication (twice a day) together with 0.1 g of ritonavir (also twice a day).

People who had previously taken medications that slowed the activity of the protease should consume 0.7 g of drugs twice a day, in combination with ritonavir (in a dose of 0.1 g twice a day).

Both dosage regimens can be used for complex treatment with other antiretroviral drugs.

Patients with a disorder of liver activity in mild or moderate form should use twice a day for 0.7 g of LS (as a monotherapy) or the same dose in combination with a single dose of 0.1 g of ritonavir per day.

People with severe forms of functional hepatic disorders should take the medicine in a dose of 0.7 g / day.

Children who have not previously been treated with antiretroviral medicines are prescribed such servings:

• category 2-5 years - taking 30 mg / kg or 20 mg / kg of Telzira in combination with ritonavir (3 mg / kg);
• category 6-18 years - use of 30 mg / kg or 18 mg / kg of the drug together with ritonavir (3 mg / kg).

Children who have not previously taken drugs that slow the activity of proteases:

• group 2-5 years - use of 20 mg / kg together with ritonavir (3 mg / kg dose);
• category 6-18 years - taking 18 mg / kg of LS in combination with ritonavir (dose 3 mg / kg).

[35]

Use It is during pregnancy

Use Telsir during pregnancy is allowed only in situations where the possible benefits for women are more likely than the risk of the fetus having negative consequences.

When breastfeeding the drug can not be used.

Contraindications

The main contraindications:

• functional hepatic disorders in moderate or severe degree;
• combination (together with ritonavir) with medications having a narrow drug index, and are the basis of the element CYP3A4, and in addition to substances whose mechanism of action proceeds with isoenzyme CYP2D6;
• combination (together with ritonavir) with rifampicin;
• the presence of intolerance in relation to amprenavir with fosamprenavir and ritonavir.

[24], [25], [26], [27], [28], [29],

Side effects It is

Taking medication can trigger the appearance of some side effects:

• disorders associated with digestive activity: often there is vomiting, abdominal pain and diarrhea with nausea, and in addition, the activity of the elements of AST and ALT increases;
• reactions affecting the central nervous system: often there are headaches;
• others: often there is an increase in the level of TG or lipase.

[30], [31], [32], [33], [34]

Overdose

The drug has no antidote. There is also no information on whether it is possible to withdraw amprenavir from the body by hemodialysis or peritoneal dialysis. If the patient develops intoxication, it should be sent to the supervision of specialists - to determine the toxicity symptoms and perform the required supporting procedures.

[36], [37], [38]

Interactions with other drugs

Fosamprenavir has a large range of therapeutic interactions, because its function is to slow the activity of isoenzymes CYP3A4, and when combined with ritonavir - also the element CYP2D6. If you want to use other drugs against the background of a treatment course that has this combination, you should remember about the possibility of the appearance of negative symptoms and change the dosage of medications and the treatment regimen accordingly.

In vitro tests show that amprenavir demonstrates synergistic effects when combined with nucleoside analogs (among them zidovudine with didanosine, and in addition abacavir), as well as with saquinavir, which slows the activity of the protease.

Simultaneous use with ritonavir, and in addition indinavir and nelfinavir leads to the fact that amprenavir begins to have an additive effect.

[39], [40], [41], [42]

Storage conditions

Tselser in tablets, as well as in the form of an oral suspension, should be kept at temperatures not exceeding 30 ° C. Suspension is prohibited from freezing. Keep medicines in a location inaccessible to young children.

[43], [44], [45]

Shelf life

Telzir (tablets) can be used for 3 years since the release of the drug. Suspension has a 2-year shelf life. The open vial can be stored for a maximum of 28 days.

[46], [47], [48], [49], [50]

Analogues

Analogues of the drug are such drugs as Aluvia, Baraclud, Viracept, Virodin, Indivir, Kaletra, Crixivan, Lopizip, Nelvir, Nelfin, Nelfiner, Norvir, Presista, Reataz, Ritam, Ritokom.

[51], [52], [53], [54], [55],