ATAZANAVIR MYLAN

Therapy should be initiated by a physician experienced in the management of HIV infection. Posology Adults The recommended dose of atazanavir is 300 mg once daily taken with ritonavir 100 mg once daily and with food. 1). 4, Withdrawal of ritonavir only under restrictive conditions.

Paediatric patients (6 years to less than 18 years of age and weighing at least 15 kg): The dose of atazanavir capsules for paediatric patients is based on body weight as shown in Table 1 and should not exceed the recommended adult dose.

Atazanavir Mylan capsules must be taken with ritonavir and have to be taken with food. Dose for paediatric patients (6 years to less than 18 years of age and weighing at least 15 kg) for Atazanavir Mylan capsules with ritonavir Body Weight (kg) Atazanavir Mylan once daily dose ritonavir once daily dosea 15 to less than 35 200 mg 100 mg at least 35 300 mg 100 mg a Ritonavir capsules, tablets or oral solution.

Paediatric patients (at least 3 months of age and weighing at least 5 kg):

Other formulations of this medicine may be available for paediatric patients at least 3 months of age and weighing at least 5 kg (see relevant Summary of Product Characteristics for alternative forms). Switching to capsules from other formulations is encouraged as soon as patients are able to consistently swallow capsules.

When transitioning between formulations, a change in dose may be needed. Consult the dosing table for the specific formulation (see relevant Summary of Product Characteristics). Special populations Renal impairment No dosage adjustment is needed.

2). Hepatic impairment Atazanavir with ritonavir has not been studied in patients with hepatic impairment. Atazanavir Mylan with ritonavir should be used with caution in patients with mild hepatic impairment. 2). 2). Unboosted atazanavir must not be used in patients with severe hepatic impairment.

Pregnancy and postpartum During the second and third trimesters of pregnancy:

Atazanavir 300 mg with ritonavir 100 mg may not provide sufficient exposure to atazanavir, especially when the activity of atazanavir or the whole regimen may be compromised due to drug resistance. Since there are limited data available and due to inter-patient variability during pregnancy, Therapeutic Drug Monitoring (TDM) may be considered to ensure adequate exposure.

Summary of the safety profile Atazanavir has been evaluated for safety in combination therapy with other antiretroviral medicinal products in controlled clinical trials in 1,806 adult patients receiving atazanavir 400 mg once daily (1,151 patients, 52 weeks median duration and 152 weeks maximum duration) or atazanavir 300 mg with ritonavir 100 mg once daily (655 patients, 96°weeks median duration and 108 weeks maximum duration).

Adverse reactions were consistent between patients who received atazanavir 400 mg once daily and patients who received atazanavir 300 mg with ritonavir 100 mg once daily, except that jaundice and elevated total bilirubin levels were reported more frequently with atazanavir plus ritonavir.

Among patients who received atazanavir 400 mg once daily or atazanavir 300 mg with ritonavir 100 mg once daily, the only adverse reactions of any severity reported very commonly with at least a possible relationship to regimens containing atazanavir and one or more NRTIs were nausea (20%), diarrhoea (10%), and jaundice (13%).

Among patients receiving atazanavir 300 mg with ritonavir 100 mg, the frequency of jaundice was 19%. 4). Chronic kidney disease in HIV-infected patients treated with atazanavir, with or without ritonavir, has been reported during postmarketing surveillance.

A large prospective observational study has shown an association between an increased incidence of chronic kidney disease and cumulative exposure to atazanavir/ritonavir- containing regimen in HIV-infected patients with an initially normal eGFR.

This association was observed independently of exposure to tenofovir disoproxil. 4). Tabulated list of adverse reactions Assessment of adverse reactions for atazanavir is based on safety data from clinical studies and post-marketing experience.

Frequency is defined using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Co-administration of atazanavir with ritonavir at doses greater than 100 mg once daily has not been clinically evaluated. The use of higher ritonavir doses may alter the safety profile of atazanavir (cardiac effects, hyperbilirubinaemia) and therefore is not recommended.

Only when atazanavir with ritonavir is co-administered with efavirenz, a dose increase of ritonavir to 200 mg once daily could be considered. In this instance, close clinical monitoring is warranted (see Interaction with other Medicinal Products below).

3). The safety and efficacy of atazanavir has not been established in patients with significant underlying liver disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.

8). Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.

If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered. Renal impairment No dosage adjustment is needed in patients with renal impairment. 2). QT prolongation Dose-related asymptomatic prolongations in PR interval with atazanavir have been observed in clinical studies.

Caution should be used with medicinal products known to induce PR prolongations. 1). 3). Haemophiliac patients There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthroses, in type A and B haemophiliac patients treated with protease inhibitors.

In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship has been suggested, although the mechanism of action has not been elucidated.

1. 2). 2). 5). 5). 4 and