Telzir

Telzir is a systemic antiviral drug, belongs to the group of protease inhibitors.

Indications Telzira

It is used for therapy of HIV infection (combination treatment with ritonavir).

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Release form

The drug is produced in tablets of 0.7 g, 60 pieces in a polyethylene bottle. There is 1 such bottle in a box.

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

Pharmacodynamics

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

The amprenavir element is a non-peptide competitive agent that inhibits the activity of HIV protease. It prevents the viral protease from cleaving the polyprotein precursors that are required for viral replication. Amprenavir selectively inhibits the replication activity of HIV-1 elements as well as HIV-2.

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Pharmacokinetics

After oral administration of Telzir, it is almost completely and rapidly hydrolyzed, acquiring the form of amprenavir, as well as an organic phosphate, after which it is absorbed through the intestinal epithelium.

Absorption.

Following repeated administration of 1.4 g twice daily, amprenavir is rapidly absorbed, with peak steady-state levels of 4.82 (range 4.06–5.72) mcg/mL and a time interval of 1.3 (range 0.8–4) hours.

The geometric mean Cmin level is 0.35 (range 0.27-0.46) μg/ml at steady state, and the AUC values are 16.6 (range 13.8-19.6) μg/ml between doses. AUC values are similar when any form of the drug is taken on an empty stomach. However, the peak plasma level of amprenavir when taken as a suspension is 14% higher than when taken as tablets.

Concomitant administration of fat-rich foods with tablets does not affect the pharmacokinetic properties of amprenavir in plasma.

Taking the suspension with fatty food reduces the AUC level by 28%, and the Cmax values by 46% (compared to taking the drug on an empty stomach). Adults should take the suspension on an empty stomach. Children and adolescents should take it with food (this is provided for by the dosage regimen for this category of patients).

Absolute bioavailability of drugs in humans is unknown.

Distribution processes.

The apparent distribution volume of amprenavir is approximately 430 L (6 L/kg, for a person weighing 70 kg). The large Vd level can be explained by the free passage of the substance into the tissues of the circulatory system.

Amprenavir is synthesized with protein at approximately 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 using the enzyme CYP3A4. Less than 1% of the drug is excreted unchanged through the kidneys.

Excretion.

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

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Dosing and administration

The drug is taken orally (tablets can be taken regardless of meal times, but the suspension can only be taken on an empty stomach).

People who have not used drugs that inhibit protease activity are prescribed 1.4 g of the drug twice a day. A regimen of taking 1.4 g of Telzir once a day in combination with 0.2 g of ritonavir (once a day) is also proposed. It is possible to take 0.7 g of the drug (twice a day) together with 0.1 g of ritonavir (also twice a day).

Individuals who have previously taken drugs that inhibit protease activity should take 0.7 g of the drug twice daily, in combination with ritonavir (in a 0.1 g dose twice daily).

Both dosage regimens can be used in combination therapy with other antiretroviral drugs.

Patients with mild to moderate liver dysfunction should take 0.7 g of the drug twice a day (as 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 liver disorders need to take the medicine in a dose of 0.7 g/day.

Children who have not previously undergone treatment with antiretroviral drugs are prescribed the following doses:

• category 2-5 years – taking 30 mg/kg or 20 mg/kg Telzir 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).

For children who have not previously taken protease inhibitors:

• 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 the drug in combination with ritonavir (dose 3 mg/kg).

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Use Telzira during pregnancy

Telzir may be used during pregnancy only in situations where the potential benefit to the woman is more likely than the risk of negative consequences for the fetus.

The drug cannot be used during breastfeeding.

Contraindications

Main contraindications:

• moderate or severe functional liver disorders;
• combination (along with ritonavir) with drugs that have a narrow drug index and are the basis of the CYP3A4 element, as well as with substances whose mechanism of action occurs with the help of the CYP2D6 isoenzyme;
• combination (together with ritonavir) with the substance rifampicin;
• presence of intolerance to amprenavir with fosamprenavir and ritonavir.

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Side effects Telzira

Taking the medicine may cause some side effects:

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

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Overdose

There is no antidote for the drug. There is also no data on whether amprenavir can be removed from the body using hemodialysis or peritoneal dialysis. If a patient develops intoxication, they should be placed under specialist observation to determine the symptoms of toxicity and perform the necessary supportive procedures.

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Interactions with other drugs

Fosamprenavir has a wide range of therapeutic interactions because its function is to slow down the activity of CYP3A4 isoenzymes, and when combined with ritonavir, also the CYP2D6 element. If it is necessary to use other drugs during a treatment course that has such a combination, it is necessary to remember the possibility of negative symptoms and change the dosages of drugs and the treatment regimen accordingly.

In vitro tests show that amprenavir exhibits synergistic effects when combined with nucleoside analogues (including zidovudine with didanosine, and also abacavir), as well as with saquinavir, which inhibits protease activity.

Concomitant use with ritonavir, and in addition indinavir and nelfinavir, results in amprenavir having an additive effect.

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Storage conditions

Telzir in tablets, as well as in the form of an oral suspension, must be kept at temperatures not exceeding 30°C. The suspension must not be frozen. Medicines should be stored in places inaccessible to small children.

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Shelf life

Telzir (tablets) can be used for 3 years from the date of release of the drug. The suspension has a 2-year shelf life. An opened bottle can be stored for a maximum of 28 days.

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Analogues

The following drugs are analogs of the drug: Aluvia, Baraclude, Virasept, Virodin, Indivir, Kaletra, Crixivan, Lopicip, Nelvir, Nelfin, Nelfiner, Norvir, Prezista, Reyataz, Ritam, Ritokom.

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