Atazanavir
When ATH:
J05AE08
Pharmacological action
Antiviral agent. Azapeptidnym is an HIV protease inhibitor. Selectively inhibits the virus-specific processing of the viral Gag-Pol proteins in HIV-infected cells, preventing the formation of mature virions and infection of other cells.
Pharmacokinetics
The data is not provided.
Testimony
HIV treatment (in combination with other antiretroviral agents).
Dosage regimen
Is the inside. The dose and regimen set depending on the composition of the combination therapy and clinical situation.
Side effect
From the central and peripheral nervous system: often – headache, insomnia, peripheral neurologic symptoms; rarely – restless dreams, memory loss, confusion, drowsiness, anxiety, depression, sleep disorders.
From the digestive system: Often – jaundice; often – stomach ache, diarrhea, dyspepsia, nausea, vomiting; rarely – dysgeusia, flatulence, gastritis, pancreatitis, thrush, dry mouth, anorexia, increased appetite, hepatitis; in some cases – hepatosplenomegaly.
On the part of the musculoskeletal system: rarely – arthralgia, muscular atrophy, myalgia; rarely – myopathy.
From the urinary system: rarely – hematuria, frequent urination, proteinuria; in some cases – pain in the kidneys, urolithiasis disease.
Allergic reactions: rarely – hives.
Dermatological reactions: often – rash; rarely – baldness, itch; rarely – vasodilation, vesiculobullous rash.
Metabolism: often – lipodystrophy; rarely – weight loss, weight gain.
From the laboratory parameters: increase in total bilirubin (with increasing prevalence of indirect bilirubin), increase the level of amylase, creatine, GOLD, IS, lipase, neutropenia.
Other: often – generalized weakness, ikterichnost sclera; rarely – chest pain, fatigue, fever, general malaise, gynecomastia.
Contraindications
Severe hepatic impairment, childhood and adolescence up 18 years, concomitant use of rifampicin, Hypersensitivity to atazanavir.
Pregnancy and lactation
There are no adequate and well-controlled studies of atazanavir during pregnancy was conducted. The use is possible in cases, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.
If necessary, use during lactation should stop breastfeeding.
Cautions
Not recommended for use together with inducers of CYP3A4 (incl. with drugs St. John's wort), with drugs, It is a substrate of CYP3A4 with narrow therapeutic range (incl. with astemizole, terfenadine, cizapridom, pimozidom, xinidinom, bepridil, ergotamine, digidroergotaminom, эrhonovynom, methylergonovine).
Not recommended simultaneous application of a combination of atazanavir ritonavir with other protease inhibitors.
To apply caution in patients with mild to moderate hepatic insufficiency, tk. Atazanavir is metabolized primarily in the liver, and there is the risk of increasing its concentration in blood plasma. Patients with hepatitis B or C, or marked prior to treatment increased levels of transaminases, increases the risk of further increase of transaminases.
When a severe skin rash discontinue use atazanovira.
Patients with hemophilia type A and B on the background of treatment with protease inhibitors described bleeding, incl. spontaneous bleeding and skin hemarthrosises. Some of these patients required infusion of factor VIII. More than half of the patients treated with protease inhibitors was continued or resumed after the break,. A causal relationship between protease inhibitor therapy and these cases has not been established.
If necessary, the simultaneous application of felodipine, nifedipine, nicardipine and verapamil shows dose titration of calcium channel blockers and monitoring of ECG.
Drug Interactions
Since atazanavir is metabolized in the liver with the participation of CYP3A4, while the use of other drugs, metabolized by isoenzyme (incl. calcium channel blockers, HMG-CoA reductase inhibitors of PDE 5, including sildenafil, tadalafil, Vardenafil) may increase the plasma concentration of a component. This may lead to increased and prolongation of the therapeutic and side effect of PDE inhibitor 5.
With simultaneous use of atazanavir with inducers of CYP3A4 (incl. rifampin) may reduce the concentration of atazanavir in plasma and reduce its effectiveness.
Rifampicin reduces the activity of most protease inhibitors about 90%.
With simultaneous use of atazanavir with inhibitors of CYP3A4 may increase the concentration of atazanavir in the blood plasma.
Efavirenz decreases the effect, while the use of atazanavir.
Expected, Chto nevirapine, CYP3A4 inducer how, capable of reducing the effect of atazanavir (concurrent use is not recommended).
Indinavir can cause hyperbilirubinemia, therefore concurrent use with atazanavir is not recommended.
In an application with atazanavir decreases the effectiveness of saquinavir.
With simultaneous use of atazanavir with ritonavir concentration in blood plasma increases.
Antacids (and preparations, containing antacids) reduce gastric acidity, so the absorption decreases atazanavir.
While the use of atazanavir may increase plasma concentrations of lidocaine (for systemic use), amiodarona (It requires special care and control of therapeutic concentrations of these drugs), xinidina (application combinations atazanavir ritonavir hinidinom contraindicated).
With simultaneous use may increase the toxicity of irinotecan due to slow its metabolism.
Not recommended simultaneous application with simvastatin and lovastatin.
Atazanavir can increase the effects of diltiazem and its metabolite desacetyl diltiazem (recommended dose reduction of diltiazem on 50% and monitoring of ECG).
In an application with bepridilom possible potentiation of severe and / or life-threatening reactions (application combinations atazanavir ritonavir bepridilom contraindicated).
Under the influence of atazanavir may increase the action of atorvastatin, cerivastatin and increased risk of myopathy, including rhabdomyolysis (Special care is required while applying).
Histamine H2-receptors and proton pump inhibitors reduce the concentration of atazanavir in plasma, that can reduce its therapeutic effectiveness or develop resistance.
At simultaneous application with cyclosporine, takrolymusom, sirolimus may increase the concentration in plasma immunosuppressants (recommended monitoring of therapeutic concentrations).
While the use of clarithromycin observed increase in the concentration of the latter in the blood plasma, that can cause QT prolongation (reduction in the dose of antibiotic required to 50%).
While the use of atazanavir increased efficiency of rifabutin (it is recommended to decrease the dose of rifabutin 75%).
Ketoconazole and itraconazole may increase the concentration of atazanavir and ritonavir plasma.
While the use of warfarin are at risk of severe and / or life-threatening bleeding due to increased activity of warfarin (INR monitoring is recommended).
