Sfumata (Capsules) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

Packaging and Quality Control Release

Biokhimik, JSC (Russia)

ATC Code

J05AE08 (Atazanavir)

Active Substance

Atazanavir (Rec.INN registered by WHO)

Dosage Forms

	Sfumata	Capsules 150 mg: 10, 12, 18, 20, 30, 36, 54, 60, 72, 90, 100 or 120 pcs.
		Capsules 200 mg: 10, 12, 18, 20, 30, 36, 54, 60, 72, 90, 100 or 120 pcs.
		Capsules 300 mg: 10, 12, 18, 20, 30, 36, 54, 60, 72, 90, 100 or 120 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin No. 1, white, cylindrical in shape with hemispherical ends; capsule contents – a mixture of granules and powder from almost white to white with a yellowish tint; the presence of lumps and rods that easily disintegrate when pressed with a glass rod is allowed.

Excipients: crospovidone – 16.5 mg, lactose monohydrate – 81 mg, sodium stearyl fumarate – 1.65 mg.

Composition of hard gelatin capsule No. 1:
Capsule body titanium dioxide (E171) – 2%, iron oxide yellow dye (E172), gelatin – up to 100%.
capsule cap: titanium dioxide (E171) – 2%, iron oxide yellow dye (E172), gelatin – up to 100%.

6 pcs. – contour cell packs (2) – cardboard packs.
6 pcs. – contour cell packs (3) – cardboard packs.
6 pcs. – contour cell packs (6) – cardboard packs.
6 pcs. – contour cell packs (9) – cardboard packs.
6 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.

Capsules hard gelatin No. 0, yellow, cylindrical in shape with hemispherical ends; capsule contents – a mixture of granules and powder from almost white to white with a yellowish tint; the presence of lumps and rods that easily disintegrate when pressed with a glass rod is allowed.

Excipients: crospovidone – 22 mg, lactose monohydrate – 108 mg, sodium stearyl fumarate – 2.2 mg.

Composition of hard gelatin capsule No. 0:
Capsule body titanium dioxide (E171) – 1%, iron oxide yellow dye (E172) – 0.5%, gelatin – up to 100%.
capsule cap: titanium dioxide (E171) – 1%, iron oxide yellow dye (E172) – 0.5%, gelatin – up to 100%.

6 pcs. – contour cell packs (2) – cardboard packs.
6 pcs. – contour cell packs (3) – cardboard packs.
6 pcs. – contour cell packs (6) – cardboard packs.
6 pcs. – contour cell packs (9) – cardboard packs.
6 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.

Capsules hard gelatin No. 1, with blue body and cap; capsule contents – a mixture of granules and powder from almost white to light yellow.

Excipients: crospovidone – 33 mg, lactose monohydrate – 162 mg, sodium stearyl fumarate – 3.3 mg.

Composition of hard gelatin capsule No. 00:
Capsule body: titanium dioxide (E171) – 2%, iron oxide yellow dye (E172), gelatin – up to 100%.
capsule cap: titanium dioxide (E171) – 2%, iron oxide yellow dye (E172), gelatin – up to 100%.

6 pcs. – contour cell packs (2) – cardboard packs.
6 pcs. – contour cell packs (3) – cardboard packs.
6 pcs. – contour cell packs (6) – cardboard packs.
6 pcs. – contour cell packs (9) – cardboard packs.
6 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – jars (1) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

Antiviral agent. It is an azapeptide inhibitor of HIV protease. It selectively inhibits virus-specific processing of viral Gag-Pol proteins in HIV-infected cells, preventing the formation of mature virions and infection of other cells.

Indications

Treatment of HIV infections (in combination with other antiretroviral drugs).

ICD codes

Dosage Regimen

Take orally once daily with food.

For treatment-naive and treatment-experienced adult patients, the standard dose is 300 mg (one 300 mg capsule) plus ritonavir 100 mg.

When used without ritonavir in treatment-naive patients unable to tolerate ritonavir, administer 400 mg (two 200 mg capsules) once daily with food.

For patients receiving concomitant efavirenz, administer atazanavir 400 mg plus ritonavir 100 mg as a single daily dose with food.

For patients receiving concomitant tenofovir, always co-administer with ritonavir; use the standard regimen of atazanavir 300 mg plus ritonavir 100 mg once daily with food.

For patients receiving concomitant H2-receptor antagonists or proton pump inhibitors, administer atazanavir simultaneously with, or at least 10 hours after, an H2-receptor antagonist; administer atazanavir 12 hours after a proton pump inhibitor.

In patients with moderate hepatic impairment (Child-Pugh Class B), reduce the dose to 300 mg once daily without ritonavir.

Do not administer to patients with severe hepatic impairment (Child-Pugh Class C).

Swallow capsules whole; do not open or crush.

Adhere strictly to the prescribed regimen to maintain effective viral suppression and prevent resistance development.

Adverse Reactions

From the CNS and peripheral nervous system common – headache, insomnia, peripheral neurological symptoms; rare – restless dreams, memory loss, confusion, drowsiness, anxiety, depression, sleep disorders.

From the digestive system very common – jaundice; common – abdominal pain, diarrhea, dyspepsia, nausea, vomiting; rare – taste perversion, flatulence, gastritis, pancreatitis, aphthous stomatitis, dry mouth, anorexia, increased appetite, hepatitis; in some cases – hepatosplenomegaly.

From the musculoskeletal system rare – arthralgia, muscle atrophy, myalgia; rare – myopathy.

From the urinary system rare – hematuria, frequent urination, proteinuria; in some cases – kidney pain, urolithiasis.

Allergic reactions rare – urticaria.

Dermatological reactions common – rash; rare – alopecia, itching; rare – vasodilation, vesiculobullous rash.

From metabolism common – lipodystrophy; rare – weight loss, weight gain.

From laboratory parameters increased total bilirubin (with a predominance of increased indirect bilirubin), increased levels of amylase, CPK, ALT, AST, lipase, neutropenia.

Other common – general weakness, icterus of the sclera; rare – chest pain, fatigue, fever, general malaise, gynecomastia.

Contraindications

Severe hepatic insufficiency, children and adolescents under 18 years of age, simultaneous use with rifampicin, hypersensitivity to atazanavir.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies of atazanavir during pregnancy have not been conducted. Use is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindication: severe hepatic insufficiency. Use with caution in patients with mild and moderate hepatic insufficiency, because Atazanavir is metabolized mainly in the liver, and there is a risk of increasing its plasma concentration. In patients with viral hepatitis B or C, or with elevated transaminase levels before the start of treatment, the risk of further increase in transaminases is increased.

Pediatric Use

Contraindication: children and adolescents under 18 years of age

Special Precautions

It is not recommended to use simultaneously with CYP3A4 inducers (including St. John’s wort preparations), with drugs that are substrates of CYP3A4 with a narrow therapeutic range (including astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, ergotamine, dihydroergotamine, ergonovine, methylergonovine).

Simultaneous use of the combination Atazanavir+ritonavir with other protease inhibitors is not recommended.

Use with caution in patients with mild and moderate hepatic insufficiency, because Atazanavir is metabolized mainly in the liver, and there is a risk of increasing its plasma concentration. In patients with viral hepatitis B or C, or with elevated transaminase levels before the start of treatment, the risk of further increase in transaminases is increased.

If a severe skin rash appears, the use of atazanavir should be discontinued.

In patients with hemophilia type A and B, bleeding, including spontaneous skin hemorrhages and hemarthrosis, has been described during treatment with protease inhibitors. Some of these patients required the administration of factor VIII. In more than half of the patients, treatment with protease inhibitors was continued or resumed after a break. A causal relationship between protease inhibitor therapy and these cases has not been established.

If simultaneous use with felodipine, nifedipine, nicardipine and verapamil is necessary, titration of the dose of calcium channel blockers and ECG monitoring are indicated.

Drug Interactions

Since Atazanavir is metabolized in the liver with the participation of the CYP3A4 isoenzyme, when used simultaneously with other drugs metabolized by this isoenzyme (including calcium channel blockers, HMG-CoA reductase inhibitors and PDE5 inhibitors, including sildenafil, tadalafil, vardenafil), an increase in the plasma concentration of one of the components is possible. This can lead to an increase and prolongation of the therapeutic and side effects of the PDE5 inhibitor.

Simultaneous use of atazanavir with inducers of the CYP3A4 isoenzyme (including rifampin) may lead to a decrease in the plasma concentration of atazanavir and a decrease in its effectiveness.

Rifampin reduces the activity of most protease inhibitors by approximately 90%.

When atazanavir is used simultaneously with inhibitors of the CYP3A4 isoenzyme, an increase in the plasma concentration of atazanavir is possible.

Efavirenz reduces the effect of atazanavir when used simultaneously.

It is assumed that nevirapine, as an inducer of CYP3A4, is able to reduce the effect of atazanavir (simultaneous use is not recommended).

Indinavir can cause hyperbilirubinemia, so simultaneous use with atazanavir is not recommended.

When used simultaneously with atazanavir, the effectiveness of saquinavir decreases.

When used simultaneously with ritonavir, the plasma concentration of atazanavir increases.

Antacids (and preparations containing antacids) reduce the acidity of gastric juice, so the absorption of atazanavir is reduced.

When used simultaneously with atazanavir, an increase in the plasma concentrations of lidocaine (for systemic use), amiodarone (special caution and monitoring of therapeutic concentrations of these drugs is required), quinidine (use of the Atazanavir+ritonavir combination with quinidine is contraindicated) is possible.

When used simultaneously, an increase in the toxicity of irinotecan is possible due to a slowdown in its metabolism.

Simultaneous use with simvastatin and lovastatin is not recommended.

Atazanavir may enhance the effect of diltiazem and its metabolite desacetyl diltiazem (a 50% reduction in the dose of diltiazem and ECG monitoring is recommended).

When used simultaneously with bepridil, potentiation of the development of severe and/or life-threatening reactions is possible (use of the Atazanavir+ritonavir combination with bepridil is contraindicated).

Under the influence of atazanavir, an enhancement of the effect of atorvastatin, cerivastatin and an increase in the risk of developing myopathy, including rhabdomyolysis, is possible (special caution is required when used simultaneously).

Histamine H₂-receptor blockers and proton pump inhibitors reduce the plasma concentration of atazanavir, which can lead to a decrease in its therapeutic effectiveness or the development of resistance.

When used simultaneously with cyclosporine, tacrolimus, sirolimus, an increase in the plasma concentrations of immunosuppressants is possible (monitoring of their therapeutic concentrations is recommended).

When used simultaneously with clarithromycin, an increase in the plasma concentration of the latter is observed, which can cause an increase in the QT interval (a 50% reduction in the antibiotic dose is required).

When used simultaneously with atazanavir, the effectiveness of rifabutin increases (a reduction in the rifabutin dose to 75% is recommended).

Ketoconazole and itraconazole may increase the plasma concentrations of atazanavir and ritonavir.

When used simultaneously with warfarin, there is a risk of severe and/or life-threatening bleeding due to increased warfarin activity (INR monitoring is recommended).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.