Telzir tablets 700 mg, 60 pcs. (Fosamprenavyr)

Latin name

Telzir

Release form

Coated tablets.

Packaging

Tablets: 60 pcs. - bottles of high density polyethylene (1) - packs of cardboard.

Pharmacological action of

Fosamprenavir is an inactive precursor of amprenavir. In the body, it hydrolyzes with the formation of inorganic phosphate and pharmacologically active amprenavir. Amprenavir is a non-peptide competitive human immunodeficiency virus (HIV) protease inhibitor that prevents the cleavage of polypeptide precursors necessary for virus replication.

Fosamprenavir has virtually no or no antiviral activity, as shown in vitro. The active metabolite, amprenavir, is a highly effective selective inhibitor of HIV-1 and HIV-2 replication. In vitro there is a synergistic effect of amprenavir when combined with nucleoside analogues (including didanosine, zidavudin, abacavir) and the protease inhibitor saquinavir. In combination with indinavir, ritonavir and nelfinavir, amprenavir has an additive effect.

With the simultaneous administration of ritonaviras by Telzir, the area under the concentration-time curve (AUC) of amprenavir increases approximately 2 times, and plasma concentrations in equilibrium (Css) - 4-6 times compared with the same values ​​after taking Telzira as monotherapy.

Prescribing Telzir in combination with ritonavir at recommended therapeutic doses increases the plasma concentration of amprenavir compared to average IC 50 values ​​in patients, including those who have never received protease inhibitors (average protein binding value of IC 50 = 0.146 μg / ml) and patients repeatedly treated with protease inhibitors (average protein binding value IC 50 = 0.90 μg / ml).

The main I50V mutation associated with amprenavir resistance is not observed in vivo. Cross-resistance to other protease inhibitors in strains resistant to amprenavir is slightly expressed, which allows continued therapy with protease inhibitors. Other mutations associated with amprenavir resistance (I54V and I84V) are rarely seen with amprenavir treatment. The amprenavir resistance profile is different from the resistance profile to other protease inhibitors. According to in vitro data, the development of amprenavir resistance is associated with a mutation at the I50V locus. Three alternative mechanisms for the development of resistance are shown in vitro and in clinical practice. The development of resistance to amirenavir can include either mutations I50V or I54L / M or V32I + I47V or, more rarely, I84V. Each of the four genetic models for the development of resistance can be accompanied by additional secondary mutations, in particular, M46I / L, which leads to the formation of viral particles with reduced sensitivity to amprenavir, some cross-resistance to ritonavir, but sensitivity to indinavir. saquinavir and nelfinavir persist. Of the 55 strains with mutations that cause resistance to protease inhibitors in vivo, 55% are sensitive to amprenavir.

The development of cross-resistance between amprenavir and reverse transcriptase inhibitors seems unlikely because these drugs act on different HIV enzymes. Telzir should not be recommended as monotherapy due to the rapid emergence of resistant viruses.

Clinical efficacy and safety

Comparison of the clinical efficacy of fosamprenavir and nelfinavir (in combination with abacavir and lamivudine, n = 249), the median plasma concentration of HIV-1 RNA decreased by 3.13 for fosamprenavir and 3.37 nelfinavir log10copy / ml at 48 weeks. Comparable efficacy of fosamprenavir and nelfinavir has been shown. The percentage of early termination of treatment due to insufficient antiviral action is as follows: 27% in the nelfinavir group and 14% in the fosamprenavir group.

A similar clinical efficacy has been demonstrated for the combination of fosamprenavir and low doses of ritonavir (single dose) with baseline therapy with abacavir and lamivudine in patients who have not previously received antiretroviral therapy compared to nelfinavir (twice daily) with baseline therapy with abacavir. In 69% of patients receiving fosamprenavir / ritonavir, the plasma HIV-1 RNA concentration was less than 400 copies / ml at 48 weeks of treatment compared with 68% of patients in the nelfinavir group. In most patients, the viral load decreased to values ​​less than 50 copies / ml - 55% in the fosamprenavir / ritonavir group and 53% in the nelfinavir group. The percentage of early termination of treatment due to insufficient antiviral action is as follows: 15% in the nelfinavir group and 4% in the fosamprenavir / ritonavir group. In the fosamprenavir / ritonavir group, there was no development of primary or secondary mutations, including those related to resistance to ritonavir or amprenavir, in contrast to the nelfinavir group, the frequency of primary and secondary mutations in which was 56%.

The frequency of mutations associated with the development of resistance to basic therapy with abacavir / lamivudine is extremely low 4/32 (13%) in the fosamprenavir + ritonavir group and significantly higher, 31/54 (57%), in the nelfinavir group (p

Lack of developing resistance or cross-resistance to other protease inhibitors on the background of the fosamprenavir / ritonavir regimen shows that treatment failure does not affect the response to combination therapy with protease inhibitors.

Comparable efficacy has been shown in patients previously treated with protease inhibitor therapy (if therapy fails) compared to basic therapy with two active reverse transcriptase inhibitors with a combination of fosamprenavir and low doses of ritonavir once (1400 mg / 200 mg) or twice (700 mg / 100 mg) per day, or (400 mg / 100 mg 2 times / day) a fixed combination of lopinavir / ritonavir. Both groups showed a similar degree of virus suppression, defined as the average area under the curve minus the initial level (AAUCMB), for the concentration of HIV-1 RNA in blood plasma after 24 weeks of treatment, averaging (log10copy / ml) - 1.48 single-dose fosamprenavir / ritonavir - 1.50 two-time regimen fosamprenavir / ritonavir and - 1. 66 lopinavir / ritonavir.

Pharmacokinetics

Telzir after oral administration is rapidly and almost completely hydrolyzed to amprenavir and organic phosphate and absorbed through the intestinal epithelium. The pharmacokinetic properties of amprenavir after simultaneous administration of Telzir and ritonavir were evaluated in healthy adult subjects and HIV-infected patients, while there was no significant difference between the two groups.

Ritonavir inhibits the metabolism of amprenavir by inhibiting CYP3A4, which leads to an increase in the concentration of amprenavir in the blood plasma.

Absorption

With repeated oral administration of Telzir at a dose of 1400 mg 2 times / day, amprenavir is rapidly absorbed. Cmax at equilibrium concentration is 4.82 (4.06-5.72) μg / ml, time to reach maximum concentration (Tmax) - 1.3 (0.8-4.0) h after administration. The geometric mean of the minimum concentration is 0.35 (0.27-0.46) μg / ml for the equilibrium state, the area under the concentration-time curve (AUC) is 16.6 (13.8-19.6) h x μg / ml in the interval between doses of the drug. The AUC value is the same when fasting with any of the dosage forms of Telzir, while the C max value of amprenaviravplasma is 14% higher after taking Telzir in the form of a suspension for internal use than after taking Telzir in tablets.

Taking Telzir tablets along with a diet rich in fats does not alter the pharmacokinetics of amprenavir in plasma compared with fasting.

The absolute bioavailability of Telzir in humans has not been established.

Distribution

The apparent volume of distribution (Vd) of amprenavir after taking Telzir is approximately 430 liters (6 L / kg, based on a body weight of 70 kg). Large Vd is due to the free penetration of amprenavir into tissues from the systemic circulation. Amprenavir binds to proteins by approximately 90%. It binds to 1 acid glycoprotein (AAG) and albumin, but has a higher affinity for AAG.

Metabolism

Fosamprenavir in the body is converted to amprenavir, which is metabolized primarily in the liver with the participation of the CYP 3A4 enzyme, less than 1% of amprenavir is excreted unchanged by the kidneys.

Excretion of

After taking Telzir, T1 / 2 of amprenavir is 7.7 hours. It is excreted as metabolites (about 75%) through the intestines and about 14% by the kidneys.

Pharmacokinetics in special clinical cases

Studies of the pharmacokinetics of amprenavir in children (over 2 years old) and adolescents do not differ from those in adults.

The pharmacokinetics of telzir in patients over 65 years of age have not been studied. When prescribing to elderly patients, it is necessary to take into account the possibility of impaired liver, kidney or heart function, concomitant diseases, as well as taking other medications.

No specific studies have been carried out for impaired renal function. Since a small amount of amprenavir (less than 1% of the therapeutic dose) is excreted unchanged by the kidneys, the effect of impaired renal function on the excretion of amprenavir should be minimal.

The main route of excretion of amprenavir is through the intestines. Currently, there is only limited data regarding the use of the drug in patients with impaired liver function.

A comparative pharmacokinetic study of HIV-1-infected adults with mild or moderate hepatic impairment receiving telzir with ritonavir and patients with normal liver function was conducted. In patients with mild impaired liver function (5-6 points on the Child-Pugh scale), there was a slight increase in AUC (22%) and similar plasma concentrations compared to patients with normal liver function. When Telzir is prescribed at a dose of 450 mg 2 times / day and ritonavir 100 mg 1 time / day, the concentration of total amprenavir in the plasma is approximately 35% lower, and the plasma concentration of unbound amprenavir is approximately 67% higher. than revealed in patients with normal liver function receiving Telzir and ritonavir 700 mg / 100 mg 2 times / day. Amprenavir clearance is also significantly reduced in patients with impaired liver function compared with patients with normal liver function. An adequate correction of the Telzir dosage regimen in patients with impaired liver function may be required.

Indications

HIV infection, as part of combination therapy with other antiretroviral agents.

Use during pregnancy and lactation

Use of Telzira during pregnancy is possible only if the expected benefits of the use outweigh the possible risks for the mother and the fetus.

Dosage and administration of

Telzir is prescribed only by a doctor who has experience in treating HIV infection. The tablets are taken orally during meals or on an empty stomach. Adults 18 years of age and older.

Low doses of ritonavir can be used to increase the concentration of amprenavir in blood plasma.

Patients who have not previously received antiretroviral therapy are advised to prescribe Telzir at a dose of 1400 mg 2 times / day or Telzir at a dose of 1400 mg 1 time / day in combination with ritonavir at a dose of 100 mg or 200 mg 1 time / day or Telzir at a dose of 700 mg 2 times / day in combination with ritonavir at a dose of 100 mg 2 times / day.

Patients who previously received antiretroviral therapy with protease inhibitors are advised to prescribe Telzir at a dose of 700 mg 2 times / day in combination with ritonavir at a dose of 100 mg 2 times / day. In this category of patients, the dosage regimen using Telzira 1 time / day is not recommended.

Both dosage regimens are applicable as part of combination therapy with other antiretroviral drugs.

Side effects

The most common adverse reactions (in more than 5% of adult patients) identified in controlled clinical trials (n = 166) were gastrointestinal disorders (nausea and diarrhea) and rash.

Most of the observed phenomena associated with fosamprenavir were mild or moderate in severity, were observed at the beginning of therapy and did not require discontinuation of the drug. For most recorded adverse events, there is no initial connection with the use of the drug, combination therapy, or the development of the disease itself.

The frequency of occurrence was determined as follows: very often ( 1/10), often ( 1/100 and <1/10), infrequently ( 1/1000 and <1/100) and rarely ( 1/10000 and < 1/1000). Most adverse reactions listed below registered in two lengthy clinical studies in adults. The list includes the most common adverse reactions associated with taking the study drug, at least moderate (grade 2 or higher) and appearing in at least 2% of patients.

From the side of metabolism and nutrition: very often - hypercholesterolemia often - hypertriglyceridemia.

From the nervous system: often - headache, paresthesia of the oral mucosa.

From the cardiovascular system: infrequently - myocardial infarction.

From the gastrointestinal tract: often - diarrhea, nausea, vomiting, abdominal pain.

From the skin and subcutaneous fat: often - a rash rarely - Stevens-Johnson syndrome, angioedema.

During treatment, erythematous and maculopapular skin rashes with or without itching may appear. The rash usually goes away spontaneously without the need to cancel therapy. Telzir should be discontinued if a generalized rash develops, as well as moderate rashes associated with systemic symptoms or damage to the mucous membranes.

From the kidneys and urinary tract: infrequently - nephrolithiasis.

General and local reactions: often - fatigue.

A similar drug safety profile was observed in a controlled study (n = 534) of a combination of fosamprenavir and low doses of ritonavir.

In children and adolescents, according to two studies of the combination of fosamprenavir and ritonavir with a nucleoside reverse transcriptase inhibitor, a safety profile similar to that of adult patients was found.

Some patients treated with protease inhibitors showed a redistribution of body fat (lipodystrophy), with a decrease in fat in the subcutaneous fat on the periphery and in the face, and an increase in visceral fat deposits, breast hypertrophy, as well as accumulation fat in the dorso-cervical region (buffalo hump).

Metabolic disorders such as hypertriglyceridemia, hypertriglyceridemia, hypercholesterolemia, insulin resistance and hyperglycemia have also been observed.

Patients treated with HIV protease inhibitors have developed diabetes, hyperglycemia, or exacerbation of existing diabetes.

An increase in CPK activity, myalgia, myositis and, rarely, rhabdomyolysis were observed in patients taking HIV protease inhibitors, in particular, in combination with nucleoside analogues.

There have been cases of increased spontaneous bleeding in patients with hemophilia treated with HIV protease inhibitors.

Clinically significant changes in laboratory parameters, possibly related to fasamprenavir therapy, may include increased ALT and AST activity, lipase, triglyceride and cholesterol concentrations.

Drug Interaction

Given that fosamprenavir undergoes parietal metabolism in the intestine, rapidly converting to amprenavir, and that the concentrations of amprenavir in blood plasma are similar after taking amprenavir and fosamprenavir pharmacovigilance Pharmacokinetic studies of the properties of fosamprenavir were performed only in adults.

Metabolic interactions (CYP3A4 isoenzyme)

Drugs that are metabolized in the same way or alter CYP3A4 activity may alter the pharmacokinetics of amprenavir. Similarly, fosamprenavir may affect the pharmacokinetics of other drugs whose metabolism is the same.

Prohibited combinations

Fosamprenavir should not be administered concurrently with CYP3A4 isoenzyme substrates having a narrow therapeutic concentration range. The combined use of such drugs and fosamprenavir can lead to competitive inhibition of the metabolism of these drugs and create conditions for the manifestation of life-threatening conditions such as cardiac arrhythmia (for example, with the preparations terfenadine, astemizole, cisapride and pimozide), prolonged sedative or effective breathing effects for example, striazolam, midazolam, diazepam, flurazepam) to spasm of peripheral vessels or ischemia (for example, with ergotamine, dihydroergotamine, ergonine and methylergonium nom).

Rifampicin reduces plasma AUC of amprenavir by approximately 82%. Similar to other protease inhibitors, it can be assumed that the parallel administration of fosamprenavir with rifampicin will also significantly reduce the plasma concentrations of amprenavir. Therefore, fosamprenavir should not be given concomitantly with rifampicin.

Interaction with antiretroviral agents

Non-nucleoside reverse transcriptase inhibitors:

Efavirenz in adults lowers the Cmax, Cmin and AUC values ​​of amprenavir to about 40%. There are no recommendations for the combined use of fosamprenavir and efavirenz.

The combined use of efavirenz (600 mg 1 time / day) with fosamprenavir and ritonavir (fosamprenavir 1400 mg 1 day and ritonavir 200 mg 1 time / day) reduced the AUC of amprenavir by 13% and Cmin by 36%. Increasing the dose of ritonavir to 300 mg 1 time / day maintains plasma concentrations of amprenavir.irom 2 times / day (fosamprenavir 700 mg 2 times / day and ritonavir 100 mg 2 times / day) The plasma concentrations of amprenavir did not change significantly.

Nevirapine: with concomitant administration of fosamprenavir 1400 mg 2 times / day and nevirapine 200 mg 2 times / day AUC, Cmax and Cminamprenavir decreased by 33%, 25% and 35%, respectively. The AUC, Cmax, and Cmin of nevirapine increased by 29%, 25%, and 34%, respectively. It is not possible to formulate recommendations for the dosage regimen of the combination of fosamprenavir and nevirapine.

In the combined use of fosamprenavir (700 mg 2 times / day) ritonavir (100 mg 2 times / day) and nevirapine (200 mg 2 times / day), the effect of nevirapine on the pharmacokinetic parameters of fosamprenavir is partially offset by ritonavir, resulting in a less significant decrease in AUC and Cminprenavir by 11% and 19%, respectively, Cmax does not change. The AUC, Cmax and Cmin of nevirapine are increased by 14%, 13% and 22%, respectively. Thus, no dosage adjustment is required with the recommended combination. There are no recommendations for single dose ritonavir and fosamprenavir.

Delavirdine: AUC, Cmax, and Cmin of delavirdine decreased by 61%, 47%, and 88%, respectively, when co-administered with amprenavir. Accordingly, the AUC, Cmax and Cmin of amprenavir increased to 130%, 40% and 125%, respectively. Due to a significant decrease in the concentrations of delavirdine, the simultaneous administration of fosamprenavir and delavirdine is not recommended. It is not possible to formulate recommendations for doses of delavirdine when co-administered with fosamprenavir.

Nucleoside / nucleotide reverse transcriptase inhibitors

With the combined use of fosamprenavir and zidovudine, didanosine, stavudine, lamivudine, abacavir and tenofovir, no dosage adjustment is necessary.

protease inhibitors

There are no specific recommendations for the dosage regimen when using fosamprenavir in combination with other protease inhibitors except ritonavir.

Lopinavir / ritonavir: Cmax, AUC and Cmin for lopinavir remained unchanged with fosamprenavir (1400 mg 2 times / day) taken together with lopinavir / ritonavir 400 mg / 100 mg 2 times / day over other doses of lopinavir / ritonavir (533 mg / 133 mg 2 times / day) Cmax, AUC and Cmin of amprenavir decreased by 13%, 26% and 42%, respectively, compared with fosamprenavir / ritonavir (700 mg / 100 mg 2 times / day for 2 weeks). The optimal dose of this combination in terms of safety and efficacy has not been established.

Indinavir: when combined with amprenavir (750 mg or 800 mg 3 times / day) and indinavir (800 mg 3 times / day) for 2 weeks, Cmax, AUC and Cmin values ​​in the steady state for amprenavir were increased by 18%. 33% and 25% respectively. Cmax, AUC and Cmin of indinavir in the steady state decreased by 22%, 38% and 27% respectively.

Saquinavir: when combined with amprenavir (750 mg or 800 mg 3 times / day) and saquinavir (800 mg 3 times / day after meals), Cmax, AUC and Cmin values ​​of amprenavir decreased by 37% during the 2 weeks , 32% and 14% respectively. Cmax increased by 21%, and the AUC and Cmin values ​​of saquinavir decreased by 19% and 48%, respectively.

Nelfinavir: when combined with amprenavir (750 mg or 800 mg 3 times / day) and nelfinavir (750 mg 3 times / day after meals), Cmax and Cmin amprenavir decreased by 14% during the 2 weeks at steady state and increased 189% respectively. Cmax, AUC and Cmin of nelfinavir in the steady state increased by 12%, 15% and 14%, respectively.

Atazanavir: co-administration of fosamprenavir / ritonavir (700 mg / 100 mg 2 times / day) and atazanavir (300 mg 1 time / day) for 10 days did not affect the equilibrium concentration of amprenavir.

integrase inhibitors

Raltegravir: co-administration of fosamprenavir (1400 mg 2 times / day) and raltegravir (400 mg 2 times / day) in healthy volunteers decreased concentrations of amprenavir (Cmin decreased by 33%) and raltegravir (Cmin decreased by 68%) in blood plasma. Coadministration of fosamprenavir (without ritonavir) and raltegravir is not recommended as this may lead to a decrease in the plasma levels of amprenavir to subtherapeutic concentrations. A decrease in the concentrations of amprenavir Sminn 19–33% and raltegravir Smin 36–54% was observed with the combined administration of fosamprenavir / ritonavir 700 mg / 100 mg 2 times / day) and raltegravir (400 mg 2 times / day). Decreases in concentrations of amprenavir Cmin by 17–50% and raltegravir Cmin by 25–41% were observed after co-administration of fosamprenavir / ritonavir (1400 mg / 100 mg 1 time / day) and raltegravir (400 mg 2 times / day). The clinical significance of this decrease is unknown.

Antibiotics / antifungal agents

Erythromycin: Theoretically, the concentrations of both drugs in plasma can be increased when combined.

Ketoconazole / Itraconazole: Amprenavir increases the concentration of ketoconazole in plasma and presumably also increases the concentration of itraconazole. High doses of ketoconazole and itraconazole (more than 200 mg / day) should not be used concomitantly with fosamprenavir without first assessing the benefit / risk ratio, and careful monitoring of the patient's condition is required.

Rifampicin: Rifampicin is a potent inducer of the CYP3A4 isoenzyme. Co-administration with amprenavir results in a decrease in the Cmin and AUC of amprenavir - by 92% and 82%, respectively. Rifampicin should not be taken with fosamprenavir.

Rifabutin: The combined use of amprenavir and rifabutin leads to a 200% increase in plasma rifabutin concentration (AUC) and an increase in the number of adverse reactions associated with rifabutin. Concomitant administration of ritonavir and rifabutin may significantly increase rifabutin concentrations. It is recommended to reduce the dose of rifabutin by at least 50% when co-administered with fosamprenavir and by at least 75% when taking fosamprenavir in combination with ritonavir. Careful medical supervision is required, and further dose reductions may be required.

Other drugs

Antacids: AUC and Cmax of amprenavir were reduced by 18% and 35%, respectively, with a simultaneous increase of Cmin (C12) by 14% with a single dose of 1400 mg fosamprenavir together with a single administration of 30 ml of antacid suspension (equivalent to 2.75 g of aluminum hydroxide and 1.8 g of hydroxide ). Dose adjustments for any of these drugs are not required when combined.

Histamine H2 receptor antagonists: The concentration of amprenavir in the blood may decrease when coadministered with histamine H2 receptor antagonists (eg, concomitant administration of ranitidine or cimetidine). Co-administration of ranitidine (single dose of 300 mg) with fosamprenavir (single dose of 1400 mg) decreases plasma AUC of amprenavir by 30% and Cmax by 51%. However, the amprenavir Cmin (C12) remains unchanged. Dose adjustments for co-administration of any of the drugs listed here are not required.

Proton pump inhibitors: the combined use of fosamprenavir 1400 mg 2 times / day and esomeprazole 20 mg / day for 14 days increased the AUC by 55% and the time to reach Cmax for 1 hour for esomeprazole without affecting Cmax. No dosage adjustment is required in this case.

Drugs with a narrow therapeutic range: with the simultaneous use of fosamprenavir with such drugs as amiodarone, quinidine, lidocaine (systemic route of administration), tricyclic antidepressants and warfarin, it is required to control the concentrations of these drugs in the blood plasma due to the possibility of development. For warfarin it is necessary to follow the international normalized ratio (INR).

The list below is an example of CYP3A4 substrates, inhibitors, or inducers that can interact with fosamprenavir when used concomitantly. The list is not exhaustive. The clinical significance of these potential interactions is unknown or not fully understood. In this regard, particular attention should be paid to monitoring the toxic effects of these drugs while taking them with fosamprenavir.

Alfuzosin: serum concentrations may be increased, which may increase the risk of hypotension.

Anticonvulsants: simultaneous administration of anticonvulsants, enzyme inducers (phenytoin, phenobarbital, carbamazepine) with fosamprenavir without co-administration with low doses of ritonavir may result in decreased plasma concentrations of amprenavir.

Benzodiazepines (alprazolam, chlorazepate, diazepam and flurazepam): their serum concentrations may increase, which may lead to increased activity.

Calcium channel blockers (amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nizoldipine and verapamil): their serum concentrations may increase, which may lead to increased activity and toxicity. It is recommended to monitor the concentrations of these drugs in the blood.

Dexamethasone: may induce CYP3A4 isoenzyme and decrease plasma concentrations of amprenavir.

Phosphodiesterase-5 Inhibitors: Sildenafil plasma concentrations can increase significantly with the use of fosamprenavir, which may increase the incidence of adverse reactions of sildenafil and other phosphodiesterase-5 inhibitors (arterial hypotension, visual impairment, priapism). Concomitant use of fosamprenavir and sildenafil, vardenafil is not recommended.

Fluticasone Propionate (Interaction with Ritonavir): A significant increase in serum concentrations of fluticasone propionate was shown with concomitant administration of 200 μg of fluticasone intranasally and 100 mg of ritonavir 2 times / day. This increase is expected to significantly increase the risk of systemic adverse reactions of fluticasone. Reports of the development of systemic side effects include Cushing's syndrome, adrenal function suppression. Such an interaction is predicted for all HCCs metabolised by the CYP3A4 isoenzyme.

Hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) inhibitors: the metabolism of the HMG-CoA reductase inhibitors (lovastatin and simvastatin) is highly dependent on CYP3A4 isoenzyme and is associated with phosamestatin because of the increased risk of myopathy, including rhabdomyolysis. Caution should be exercised with fosamprenavir satorvastatin, which is also metabolised, although to a lesser extent, than lovastatin and simvastatin, via the CYP3A4 isoenzyme. The recommended dose of atorvastatin is no more than 20 mg / day. The metabolism of pravastatin ifluvastatin is independent of the CYP3A4 isoenzyme, so it is likely that that in this case there is no interaction with protease inhibitors. Pravastatin and fluvastatin are recommended when therapy with the use of the HMG-CoA reductase inhibitor group is indicated.

Immunosuppressants: Plasmecyclosporine, rapamycin and tacrolimus concentrations can be expected to be increased when co-administered with fosamprenavir. For this reason, it is recommended that the therapeutic concentrations of these drugs be monitored frequently until the levels become stable.

Bepridil: it is necessary to avoid the simultaneous administration of the combination of fosamprenavir / ritonavir and bepridil due to the fact that amprenavir and ritonavir are inhibitors of cytochrome CYP3A4, which is involved in the metabolism of bepridil, which may lead to increased concentrations of beipril and .

Methadone: Amprenavir lowers plasma methadone concentration. When methadone is co-administered with fosamprenavir, continuous monitoring of patients is required in connection with the possibility of developing withdrawal syndrome after opiate withdrawal and at the same time monitor plasma methadone concentration.

Paroxetine: Paroxetine serum concentrations can be significantly reduced when co-administered with fosamprenavir and ritonavir, so adequate adjustment of paroxetine dosing regimen is required depending on clinical effect and tolerability.

Steroid drugs: estrogens, progestogens and some ACS may interact with amprenavir. However, there is no evidence of such interaction. Due to the possibility of metabolic interaction with amprenavir, the effectiveness of hormonal contraceptives may change. Therefore, alternative methods of preventing pregnancy are recommended for women of reproductive age.

Hypericum perforated preparations: concentrations of amprenavir in the blood may be reduced due to the concomitant use of Hypericum perforatum, which is related to the induction of metabolizing enzymes by perforated perforated preparations. In this regard, St. John's wort preparations should not be used concomitantly with fosamprenavir therapy. The induction effect of St. John's wort may persist for 2 weeks after its abolition.

Overdose

There is no known antidote to Telsir. There are also no data regarding the possibility of eliminating amprenavir from the blood plasma by peritoneal dialysis and hemodialysis. In the case of overdose monitoring for the detection of symptoms of toxic effects and standard symptomatic therapy, if necessary.

Storage conditions

The drug should be stored at a temperature not exceeding 30 ° C and do not freeze.

Open the bottle for no more than 28 days.

Keep out of the reach of children.

Expiration

2 years.

Deystvuyuschee substances

Phosamprenavir

Dosage form

Dosage form

tablets



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