Atazanavir Mylan

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

  



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1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 150 mg hard capsules  

Atazanavir Mylan 200 mg hard capsules 

Atazanavir Mylan 300 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

150 mg capsules 

 

Each capsule contains 150 mg atazanavir (as sulphate) 

 

200 mg capsules 

 

Each capsule contains 200 mg atazanavir (as sulphate) 

 

300 mg capsules 

 

Each capsule contains 300 mg atazanavir (as sulphate) 

 

Excipient(s) with known effect 

 

150 mg capsules 

 

Each capsule contains 84 mg lactose monohydrate 

 

200 mg capsules 

 

Each capsule contains 112 mg lactose monohydrate 

 

300 mg capsules 

 

Each capsule contains 168 mg lactose monohydrate 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard capsule  

 

150 mg capsules 

 

Atazanavir Mylan 150 mg capsules are greenish-blue and blue opaque hard shell gelatin capsules filled with 

white to pale yellow powder and approximately 19.3 mm in length. The capsules are axially printed with 

‘MYLAN’ over ‘AR150’ in black ink on cap and body.   

 

200 mg capsules 

 

Atazanavir Mylan 200 mg capsules are blue and greenish-blue opaque hard shell gelatin capsules filled with 

white to pale yellow powder and approximately 21.4 mm in length. The capsules are axially printed with 

‘MYLAN’ over ‘AR200’ in black ink on cap and body. 

 



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300 mg capsules 

 

Atazanavir Mylan 300 mg capsules are red and greenish-blue opaque hard shell gelatine capsules filled with 

white to pale yellow powder and approximately 23.5 mm in length. The capsules are axially printed with 

‘MYLAN’ over ‘AR300’ in black ink on cap and body. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Atazanavir Mylan, co-administered with low dose ritonavir, is indicated for the treatment of HIV-1 infected 

adults and paediatric patients 6 years of age and older in combination with other antiretroviral medicinal 

products (see section 4.2). 

 

Based on available virological and clinical data from adult patients, no benefit is expected in patients with 

strains resistant to multiple protease inhibitors (≥ 4 PI mutations).  

 

The choice of Atazanavir Mylan in treatment experienced adult and paediatric patients should be based on 

individual viral resistance testing and the patient’s treatment history (see sections 4.4 and 5.1). 

 

4.2 Posology and method of administration 

 

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. Ritonavir is used as a booster of atazanavir pharmacokinetics (see sections 4.5 and 5.1). See also 

section 4.4, 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.  

 

Table 1:  Dose for paediatric patients (6 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). 

 



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Special populations 

 

Renal impairment 

No dosage adjustment is needed. Atazanavir Mylan with ritonavir is not recommended in patients 

undergoing haemodialysis (see sections 4.4 and 5.2). 

 

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. Atazanavir Mylan with 

ritonavir must not be used in patients with moderate to severe hepatic impairment (see sections 4.3, 4.4, and 

5.2).  

 

In case of withdrawal of ritonavir from the initial recommended ritonavir boosted regimen (see section 4.4), 

unboosted atazanavir could be maintained in patients with mild hepatic impairment at a dose of 400 mg and 

in patients with moderate hepatic impairment with a reduced dose of 300 mg once daily with food (see 

section 5.2). 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.  

 

The risk of a further decrease in atazanavir exposure is expected when atazanavir is given with medicinal 

products known to reduce its exposure (e.g., tenofovir disoproxil or H2-receptor antagonists). 

  

• If tenofovir disoproxil or an H2-receptor antagonist is needed, a dose increase to atazanavir 400 mg with 
ritonavir 100 mg with TDM may be considered (see sections 4.6 and 5.2).  

• It is not recommended to use atazanavir with ritonavir for pregnant patients who are receiving both 
tenofovir disoproxil and an H2-receptor antagonist.  

 

(See section 4.4, Withdrawal of ritonavir only under restrictive conditions) 

 

During postpartum 

Following a possible decrease in atazanavir exposure during the second and third trimester, atazanavir 

exposures might increase during the first two months after delivery (see section 5.2). Therefore, postpartum 

patients should be closely monitored for adverse reactions.  

 

During this time, postpartum patients should follow the same dose recommendation as for non-pregnant 

patients, including those for co-administration of medicinal products known to affect atazanavir exposure 

(see section 4.5). 

 

Paediatric patients (less than 3 months of age) 

Atazanavir Mylan should not be used in children less than 3 months because of safety concerns especially 

taking into account the potential risk of kernicterus. 

 

Method of administration  

 

For oral use. The capsules should be swallowed whole.  

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 



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Atazanavir Mylan is contraindicated in patients with severe hepatic insufficiency (see sections 4.2, 4.4 and 

5.2). Atazanavir Mylan with ritonavir is contraindicated in patients with moderate hepatic insufficiency (see 

sections 4.2, 4.4 and 5.2). 

 

Co-administration with simvastatin or lovastatin (see section 4.5).  

 

Combination of rifampicin (see section 4.5).  

 

Combination of the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension 

(PAH) only (see section 4.5). For co-administration of sildenafil for the treatment of erectile dysfunction see 

sections 4.4 and 4.5.  

 

Co-administration with medicinal products that are substrates of the CYP3A4 isoform of cytochrome P450 

and have narrow therapeutic windows (e.g., quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, 

cisapride, pimozide, quinidine, bepridil, triazolam, midazolam administered orally (for caution on 

parenterally administered midazolam, see section 4.5), and ergot alkaloids, particularly, ergotamine, 

dihydroergotamine, ergonovine, methylergonovine) (see section 4.5).  

 

Co-administration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose 

combination (see section 4.5). 

 

Co-administration with glecaprevir/pibrentasvir fixed dose combination (see section 4.5) 

 

Co-administration with products containing St. John’s wort (Hypericum perforatum) (see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk 

of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be 

taken in accordance with national guidelines.  

 

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).  

 

Patients with coexisting conditions 

 

Hepatic impairment 

Atazanavir is primarily hepatically metabolised and increased plasma concentrations were observed in 

patients with hepatic impairment (see sections 4.2 and 4.3). 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. In case of concomitant antiviral therapy for hepatitis B or C, please refer also to 

the relevant Summary of Product Characteristics for these medicinal products (see section 4.8).  

 

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. However, Atazanavir Mylan is not 

recommended in patients undergoing haemodialysis (see sections 4.2 and 5.2).  

 



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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. In patients with 

pre-existing conduction problems (second degree or higher atrioventricular or complex bundle-branch 

block), Atazanavir Mylan should be used with caution and only if the benefits exceed the risk (see section 

5.1). Particular caution should be used when prescribing Atazanavir Mylan in association with medicinal 

products which have the potential to increase the QT interval and/or in patients with pre-existing risk factors 

(bradycardia, long congenital QT, electrolyte imbalances (see sections 4.8 and 5.3).  

 

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. Haemophiliac patients should therefore be made aware of the 

possibility of increased bleeding.  

 

Weight and metabolic parameters 

 

An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such 

changes may in part be linked to the disease control and life style. For lipids, there is in some cases evidence 

for a treatment effect, while for weight gain there is no strong evidence relating this to any particular 

treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment 

guidelines. Lipid disorders should be managed as clinically appropriate.  

 

In clinical studies, atazanavir (with or without ritonavir) has been shown to induce dyslipidaemia to a lesser 

extent than comparators.  

 

Hyperbilirubinaemia 

 

Reversible elevations in indirect (unconjugated) bilirubin related to inhibition of UDP-glucuronosyl 

transferase (UGT) have occurred in patients receiving atazanavir (see section 4.8). Hepatic transaminase 

elevations that occur with elevated bilirubin in patients receiving Atazanavir Mylan should be evaluated for 

alternative aetiologies. Alternative antiretroviral therapy to Atazanavir Mylan may be considered if jaundice 

or scleral icterus is unacceptable to a patient. Dose reduction of atazanavir is not recommended because it 

may result in a loss of therapeutic effect and development of resistance.  

 

Indinavir is also associated with indirect (unconjugated) hyperbilirubinaemia due to inhibition of UGT. 

Combinations of atazanavir and indinavir have not been studied and co-administration of these medicinal 

products is not recommended (see section 4.5).  

 

Withdrawal of ritonavir only under restrictive conditions 

 

The recommended standard treatment is atazanavir boosted with ritonavir, ensuring optimal pharmacokinetic 

parameters and level of virologic suppression. 

 

The withdrawal of ritonavir from the boosted regimen of atazanavir is not recommended, but may be 

considered in adults patients at the dose of 400 mg once daily with food only under the following combined 

restrictive conditions: 

• absence of prior virologic failure 

• undetectable viral load during the last 6 months under current regimen 

• viral strains not harbouring HIV resistance-associated mutations (RAMs) to current regimen. 

 

Atazanavir given without ritonavir should not be considered in patients treated with a backbone regimen 

containing tenofovir disoproxil and with other concomitant medications that reduce atazanavir bioavailability 



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(see section 4.5 In case of withdrawal of ritonavir from the recommended atazanavir boosted regimen) or in 

case of perceived challenging compliance. 

 

Atazanavir given without ritonavir should not be used in pregnant patients given that it could result of 

suboptimal exposure of particular concern for the mother infection and vertical transmission. 

 

Cholelithiasis  

 

Cholelithiasis has been reported in patients receiving atazanavir (see section 4.8). Some patients required 

hospitalization for additional management and some had complications. If signs or symptoms of 

cholelithiasis occur, temporary interruption or discontinuation of treatment may be considered.  

 

Chronic kidney disease 

 

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. Regular monitoring of the renal 

function of patients should be maintained throughout the treatment duration (see section 4.8). 

 

Nephrolithiasis 

 

Nephrolithiasis has been reported in patients receiving atazanavir (see section 4.8). Some patients required 

hospitalization for additional management and some had complications. In some cases, nephrolithiasis has 

been associated with acute renal failure or renal insufficiency. If signs or symptoms of nephrolithiasis occur, 

temporary interruption or discontinuation of treatment may be considered.  

 

Immune reactivation syndrome 

 

In HIV-infected patients with severe immune deficiency at the time of institution of combination 

antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 

pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such 

reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples 

are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii 

pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary. 

Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur 

in the setting of immune reactivation; however, the reported time to onset is more variable and these events 

can occur many months after initiation of treatment.  

 

Osteonecrosis 

 

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, 

severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly 

in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy 

(CART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint 

stiffness or difficulty in movement.  

 

Rash and associated syndromes 

 

Rashes are usually mild -to-moderate maculopapular skin eruptions that occur within the first 3 weeks of 

starting therapy with atazanavir.  

 

Stevens-Johnson syndrome (SJS), erythema multiforme, toxic skin eruptions and drug rash with eosinophilia 

and systemic symptoms (DRESS) syndrome have been reported in patients receiving atazanavir. Patients 



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should be advised of the signs and symptoms and monitored closely for skin reactions. Atazanavir should be 

discontinued if severe rash develops.  

 

The best results in managing these events come from early diagnosis and immediate interruption of any 

suspect medicines. If the patient has developed SJS or DRESS associated with the use of atazanavir, 

atazanavir may not be restarted.  

 

Interactions with other medicinal products 

 

The combination of Atazanavir Mylan with atorvastatin is not recommended (see section 4.5).  

 

Co-administration of Atazanavir Mylan with nevirapine or efavirenz is not recommended (see section 4.5).  

If the co-administration of Atazanavir Mylan with an NNRTI is required, an increase in the dose of both 

Atazanavir Mylan and ritonavir to 400 mg and 200 mg, respectively, in combination with efavirenz could be 

considered with close clinical monitoring.  

 

Atazanavir is metabolised principally by CYP3A4. Co-administration of Atazanavir Mylan and medicinal 

products that induce CYP3A4 is not recommended (see sections 4.3 and 4.5).  

 

PDE5 inhibitors used for the treatment of erectile dysfunction: particular caution should be used when 

prescribing PDE5-inhibitors (sildenafil, tadalafil, or vardenafil) for the treatment of erectile dysfunction in 

patients receiving Atazanavir Mylan. Co-administration of Atazanavir Mylan with these medicinal products 

is expected to substantially increase their concentrations and may result in PDE5-associated adverse 

reactions such as hypotension, visual changes and priapism (see section 4.5).  

 

Co-administration of voriconazole and Atazanavir Mylan with ritonavir is not recommended, unless an 

assessment of the benefit/risk justifies the use of voriconazole.  

 

In the majority of patients, a reduction in both voriconazole and atazanavir exposures are expected. In a 

small number of patients without a functional CYP2C19 allele, significantly increased voriconazole 

exposures are expected (see section 4.5).  

 

Concomitant use of Atazanavir Mylan/ritonavir and fluticasone or other glucocorticoids that are metabolised 

by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic 

corticosteroid effects, including Cushing’s syndrome and adrenal suppression (see section 4.5).  

 

Concomitant use of salmeterol and Atazanavir Mylan may result in increased cardiovascular adverse events 

associated with salmeterol. Co-administration of salmeterol and Atazanavir Mylan is not recommended (see 

section 4.5).  

 

The absorption of atazanavir may be reduced in situations where gastric pH is increased irrespective of 

cause.  

 

Co-administration of Atazanavir Mylan with proton pump inhibitors is not recommended (see section 4.5). If 

the combination of Atazanavir Mylan with a proton pump inhibitor is judged unavoidable, close clinical 

monitoring is recommended in combination with an increase in the dose of atazanavir to 400 mg with 

100 mg of ritonavir; doses of proton pump inhibitors comparable to omeprazole 20 mg should not be 

exceeded.  

 

Co-administration of atazanavir with other hormonal contraceptives or oral contraceptives containing 

progestogens other than norgestimate or norethindrone has not been studied, and therefore should be avoided 

(see section 4.5).  

 

Paediatric population 

 

Safety 



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Asymptomatic PR interval prolongation was more frequent in paediatric patients than adults. Asymptomatic 

first- and second-degree AV block was reported in paediatric patients (see section 4.8). Caution should be 

used with medicinal products known to induce PR prolongations. In paediatric patients with pre-existing 

conduction problems (second degree or higher atrioventricular or complex bundle-branch block), Atazanavir 

Mylan should be used with caution and only if the benefits exceed the risk. Cardiac monitoring is 

recommended based on the presence of clinical findings (e.g., bradycardia).  

 

Efficacy 

Atazanavir/ritonavir is not effective in viral strains harbouring multiple mutations of resistance. 

 

Excipients 

 

Lactose 

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose 

malabsorption should not take this medicinal product.  

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

When atazanavir and ritonavir are co-administered, the metabolic drug interaction profile for ritonavir may 

predominate because ritonavir is a more potent CYP3A4 inhibitor than atazanavir. The Summary of Product 

Characteristics for ritonavir must be consulted before initiation of therapy with atazanavir and ritonavir.  

 

Atazanavir is metabolised in the liver through CYP3A4. It inhibits CYP3A4. Therefore, atazanavir is 

contraindicated with medicinal products that are substrates of CYP3A4 and have a narrow therapeutic index: 

quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, 

orally administered midazolam, and ergot alkaloids, particularly ergotamine and dihydroergotamine (see 

section 4.3). 

  

Co-administration of atazanavir with grazoprevir-containing products, including elbasvir/grazoprevir fixed 

dose combination is contraindicated because of the increase in grazoprevir and elbasvir plasma 

concentrations and potential for the increase in risk of ALT elevations associated with increased grazoprevir 

concentrations (see section 4.3). 

 

Co-administration of atazanavir with glecaprevir/pibrentasvir fixed dose combination is 

contraindicated because of the potential increase in the risk of ALT elevations due to a significant 

increase in glecapreir and pibrentasvir plasma concentrations (see section 4.3). 

 

Other interactions 

 

Interactions between atazanavir and other medicinal products are listed in the table below (increase is 

indicated as “↑”, decrease as “↓”, no change as “↔”). If available, 90% confidence intervals (CI) are shown 

in parentheses. The studies presented in Table 2 were conducted in healthy subjects unless otherwise noted. 

Of importance, many studies were conducted with unboosted atazanavir, which is not the recommended 

regimen of atazanavir (see section 4.4).  

 

If withdrawal of ritonavir is medically warranted under restrictive conditions (see section 4.4), special 

attention should be given to atazanavir interactions that may differ in the absence of ritonavir (see 

information below Table 2). 

 

Table 2:  Interactions between atazanavir and other medicinal products 

 

Medicinal products by 

therapeutic area 

Interaction Recommendations 

concerning co-

administration 

ANTI-HCV AGENTS 



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Grazoprevir 200 mg once daily 

(atazanavir 300 mg / ritonavir 

100 mg once daily) 

Atazanavir AUC: ↑43% (↑30% ↑57%) 

Atazanavir Cmax: ↑12% (↑1% ↑24%) 

Atazanavir Cmin: ↑23% (↑13% ↑134%) 

 

Grazoprevir AUC: ↑958% (↑678% ↑1339%) 

Grazoprevir Cmax: ↑524% (↑342% ↑781%) 

Grazoprevir Cmin: ↑1064% (↑696% ↑1602%) 

Grazoprevir concentrations were greatly 

increased when co-administered with 

atazanavir/ritonavir. 

Co-administration of 

atazanavir and 

elbasvir/grazoprevir 

is contraindicated 

because of a 

significant increase 

in grazoprevir 

plasma 

concentrations and 

an associated 

potential increase in 

the risk of ALT 

elevations 

(see section 4.3). 

Elbasvir 50 mg once daily 

(atazanavir 300 mg / ritonavir 

100 mg once daily) 

 

Atazanavir AUC: ↑7% (↓2% ↑17%) 

Atazanavir Cmax: ↑2% (↓4% ↑8%) 

Atazanavir Cmin: ↑15% (↑2% ↑29%) 

Elbasvir AUC: ↑376% (↑307% ↑456%) 

Elbasvir Cmax: ↑315% (↑246% ↑397%) 

Elbasvir Cmin: ↑545% (↑451% ↑654%) 

Elbasvir concentrations were increased when 

co-administered with atazanavir/ritonavir. 

Sofosbuvir 400 mg / 

velpatasvir 100 

mg/voxilaprevir 100 mg single 

dose* 

(atazanavir 300 mg / ritonavir 

100 mg once daily) 

Sofosbuvir AUC: ↑40% (↑25% ↑57%) 

Sofosbuvir Cmax:↑29% (↑9% ↑52%) 

 

Velpatasvir AUC: ↑93% (↑58% 

↑136%) 

Velpatasvir Cmax: ↑29% (↑7% ↑56%) 

 

Voxilaprevir AUC: ↑331% (↑276% 

↑393%) 

Voxilaprevir Cmax: ↑342% (↑265% 

↑435%) 

Co-administration 

of atazanavir with 

voxilaprevir- 

containing products 

is expected to 

increase the 

concentration of 

voxilaprevir. Co-

administration of 

atazanavir with 

voxilaprevir-

containing regimens 

is not 

recommended. 

 *Lack of pharmacokinetics interaction bounds 

70-143% 

 

 
Effect on atazanavir and ritonavir exposure 

has not been studied. 
Expected: 

↔ Atazanavir 

↔ Ritonavir 

 



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The mechanism of interaction between 

atazanavir/ritonavir and 

sofosbuvir/velpatasvir/voxilaprevir is 

inhibition of OATP1B, Pgp, and CYP3A. 

 

Glecaprevir 300 mg / 

pibrentasvir 120 mg once daily 

(atazanavir 300 mg / ritonavir 100 

mg once daily*) 

Glecaprevir AUC: ↑553% (↑424% ↑714%) 

Glecaprevir Cmax: ↑306% (↑215% ↑423%) 

Glecaprevir Cmin: ↑1330% (↑885% ↑1970%) 

 

Pibrentasvir AUC: ↑64% (↑48% ↑82%)  

Pibrentasvir Cmax: ↑29% (↑15% ↑45%) 

Pibrentasvir Cmin: ↑129% (↑95% ↑168%) 

* Effect of atazanavir and ritonavir on the 

first dose of glecaprevir and pibrentasvir is 

reported. 

Co-administration of 

atazanavir with 

glecaprevir/pibrentas

vir is contraindicated 

because of the 

potential increase in 

the risk of ALT 

elevations due to a 

significant increase 

in glecaprevir and 

pibrentasvir plasma 

concentrations (see 

section 4.3) 

ANTI-RETROVIRALS 

Protease inhibitors: The co-administration of atazanavir/ritonavir and other protease inhibitors has not been 

studied but would be expected to increase exposure to other protease inhibitors. Therefore, such 

co-administration is not recommended.  

Ritonavir 100 mg once daily 

(atazanavir 300 mg once daily)  

Studies conducted in HIV-infected 

patients.  

Atazanavir AUC: ↑250% (↑144% ↑403%)*  

Atazanavir Cmax: ↑120% (↑56% ↑211%)*  

Atazanavir Cmin: ↑713% (↑359% ↑1339%)*  

* In a combined analysis, atazanavir 300 mg and 

ritonavir 100 mg (n=33) was compared to 

atazanavir 400 mg without ritonavir (n=28).  

The mechanism of interaction between atazanavir 

and ritonavir is CYP3A4 inhibition.  

Ritonavir 100 mg 

once daily is used as 

a booster of 

atazanavir 

pharmacokinetics. 

Indinavir Indinavir is associated with indirect unconjugated 

hyperbilirubinaemia due to inhibition of UGT.  

Co-administration of 

atazanavir and 

indinavir is not 

recommended (see 

section 4.4).  

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) 

Lamivudine 150 mg twice daily 

+ zidovudine 300 mg twice daily  

(atazanavir 400 mg once daily)  

No significant effect on lamivudine and 

zidovudine concentrations was observed.  

Based on these data 

and because ritonavir 

is not expected to 

have a significant 

impact on the 

pharmacokinetics of 

NRTIs, the co-

administration of 

these medicinal 

products and 

atazanavir is not 

expected to 

significantly alter the 



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exposure of the co-

administered 

medicinal products.  

Abacavir The co-administration of abacavir and atazanavir 

is not expected to significantly alter the exposure 

of abacavir.  

  

Didanosine (buffered tablets) 

200 mg/stavudine 40 mg, both 

single dose  

(atazanavir 400 mg single dose)  

Atazanavir, simultaneous administration with 

ddI+d4T (fasted)  

Atazanavir AUC ↓87% (↓92% ↓79%)  

Atazanavir Cmax ↓89% (↓94% ↓82%)  

Atazanavir Cmin ↓84% (↓90% ↓73%)  

Atazanavir, dosed 1 hr after ddI+d4T (fasted)  

Atazanavir AUC ↔3% (↓36% ↑67%)  

Atazanavir Cmax ↑12% (↓33% ↑18%)  

Atazanavir Cmin ↔3% (↓39% ↑73%)  

Atazanavir concentrations were greatly decreased 

when co-administered with didanosine (buffered 

tablets) and stavudine. The mechanism of 

interaction is a reduced solubility of atazanavir 

with increasing pH related to the presence of 

anti-acid agent in didanosine buffered tablets.  

No significant effect on didanosine and stavudine 

concentrations was observed.  

Didanosine should 

be taken at the fasted 

state 2 hours after 

atazanavir taken with 

food. The co-

administration of 

stavudine with 

atazanavir is not 

expected to 

significantly alter the 

exposure of 

stavudine.  

Didanosine (enteric coated 

capsules) 400 mg single dose  

(atazanavir 300 mg once daily 

with ritonavir 100 mg once daily)  

Didanosine (with food)  

Didanosine AUC ↓34% (↓41% ↓27%)  

Didanosine Cmax ↓38% (↓48% ↓26%)  

Didanosine Cmin ↑25% (↓8% ↑69%)  

No significant effect on atazanavir concentrations 

was observed when administered with 

enteric-coated didanosine, but administration 

with food decreased didanosine concentrations.  

Tenofovir disoproxil fumarate 

300 mg once daily  

(atazanavir 300 mg once daily 

with ritonavir 100 mg once daily)  

 

300 mg tenofovir disoproxil 

fumarate is equivalent to 245 mg 

tenofovir disoproxil. 

 

Atazanavir AUC ↓22% (↓35% ↓6%) *  

Atazanavir Cmax ↓16% (↓30% ↔0%) *  

Atazanavir Cmin ↓23% (↓43% ↑2%) *  

* In a combined analysis from several clinical 

studies, atazanavir/ritonavir 300/100 mg co-

administered with tenofovir disoproxil fumarate 

When co-

administered with 

tenofovir disoproxil 

fumarate, it is 

recommended that 

atazanavir 300 mg be 

given with ritonavir 

100 mg and 

tenofovir disoproxil 

fumarate 300 mg (all 



13 

Studies conducted in HIV-infected 

patients  

300 mg (n=39) was compared to 

atazanavir/ritonavir 300/100 mg (n=33).  

The efficacy of atazanavir/ritonavir in 

combination with tenofovir disoproxil fumarate 

in treatment-experienced patients has been 

demonstrated in clinical study 045 and in 

treatment naive patients in clinical study 138 (see 

sections 4.8 and 5.1). The mechanism of 

interaction between atazanavir and tenofovir 

disoproxil fumarate is unknown.  

as a single dose with 

food). 

Tenofovir disoproxil fumarate 

300 mg once daily  

(atazanavir 300 mg once daily 

with ritonavir 100 mg once daily)  

 

300 mg tenofovir disoproxil 

fumarate is equivalent to 245 mg 

tenofovir disoproxil. 

Tenofovir disoproxil fumarate AUC ↑37% (↑30% 

↑45%)  

Tenofovir disoproxil fumarate Cmax ↑34% (↑20% 

↑51%)  

Tenofovir disoproxil fumarate Cmin ↑29% (↑21% 

↑36%)  

Patients should be 

closely monitored 

for tenofovir 

disoproxil 

fumarate-associated 

adverse reactions, 

including renal 

disorders.  

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) 

Efavirenz 600 mg once daily  

(atazanavir 400 mg once daily 

with ritonavir 100 mg once daily)  

Atazanavir (pm): all administered with food  

Atazanavir AUC ↔0% (↓9% ↑10%)*  

Atazanavir Cmax ↑17% (↑8% ↑27%)*  

Atazanavir Cmin ↓42% (↓51% ↓31%)*  

Co-administration of 

efavirenz and 

atazanavir is not 

recommended (see 

section 4.4)  

Efavirenz 600 mg once daily  

(atazanavir 400 mg once daily 

with ritonavir 200 mg once daily)  

Atazanavir (pm): all administered with food  

Atazanavir AUC ↔6% (↓10% ↑26%) */**  

Atazanavir Cmax ↔9% (↓5% ↑26%) */**  

Atazanavir Cmin ↔12% (↓16% ↑49%) */**  

* When compared to Atazanavir 

300 mg/ritonavir 100 mg once daily in the 

evening without efavirenz. This decrease in 

atazanavir Cmin, might negatively impact the 

efficacy of atazanavir. The mechanism of 

efavirenz/atazanavir interaction is CYP3A4 

induction.  

** Based on historical comparison.  

Nevirapine 200 mg twice daily  

(atazanavir 400 mg once daily 

with ritonavir 100 mg once daily)  

Study conducted in HIV infected 

patients  

Nevirapine AUC ↑26% (↑17% ↑36%)  

Nevirapine Cmax ↑21% (↑11% ↑32%)  

Nevirapine Cmin ↑35% (↑25% ↑47%)  

Atazanavir AUC ↓19% (↓35% ↑2%) *  

Co-administration of 

nevirapine and 

atazanavir is not 

recommended (see 

section 4.4)  



14 

Atazanavir Cmax ↔2% (↓15% ↑24%) *  

Atazanavir Cmin ↓59% (↓73% ↓40%) *  

* When compared to atazanavir 300 mg and 

ritonavir 100 mg without nevirapine. This 

decrease in atazanavir Cmin, might negatively 

impact the efficacy of atazanavir. The mechanism 

of nevirapine/atazanavir interaction is CYP3A4 

induction.  

Integrase Inhibitors  

Raltegravir 400 mg twice daily  

(atazanavir/ritonavir)  

Raltegravir AUC↑ 41% Raltegravir Cmax↑ 24%  

Raltegravir C12hr↑ 77%  

The mechanism is UGT1A1 inhibition.  

No dose adjustment 

required for 

raltegravir.  

HCV Protease Inhibitors  

Boceprevir 800 mg three times 

daily  

(atazanavir 300 mg/ritonavir 

100 mg once daily)  

boceprevir AUC ↔5%  

boceprevir Cmax ↔7%  

boceprevir Cmin ↔18% 

  

atazanavir AUC ↓ 35%  

atazanavir Cmax ↓ 25%  

atazanavir Cmin ↓ 49% 

  

ritonavir AUC ↓ 36%  

ritonavir Cmax ↓ 27%  

ritonavir Cmin ↓ 45%  

Co-administration of 

atazanavir/ritonavir 

with boceprevir 

resulted in lower 

exposure of 

atazanavir which 

may be associated 

with lower efficacy 

and loss of HIV 

control. This co-

administration might 

be considered on a 

case by case basis if 

deemed necessary, in 

patients with 

suppressed HIV viral 

loads and with HIV 

viral strain without 

any suspected 

resistance to the HIV 

regimen. Increased 

clinical and 

laboratory 

monitoring for HIV 

suppression is 

warranted.  

ANTIBIOTICS 

Clarithromycin 500 mg twice 

daily  

(atazanavir 400 mg once daily)  

Clarithromycin AUC ↑94% (↑75% ↑116%)  

Clarithromycin Cmax ↑50% (↑32% ↑71%)  

Clarithromycin Cmin ↑160% (↑135% ↑188%)  

 

14-OH clarithromycin  

14-OH clarithromycin AUC ↓70% (↓74% ↓66%)  

14-OH clarithromycin Cmax ↓72% (↓76% ↓67%)  

No recommendation 

regarding dose 

reduction can be 

made; therefore, 

caution should be 

exercised if 

atazanavir is 

co-administered with 

clarithromycin.  



15 

14-OH clarithromycin Cmin ↓62% (↓66% ↓58%) 

  

Atazanavir AUC ↑28% (↑16% ↑43%)  

Atazanavir Cmax ↔6% (↓7% ↑20%)  

Atazanavir Cmin ↑91% (↑66% ↑121%)  

A dose reduction of clarithromycin may result in 

subtherapeutic concentrations of 14-OH 

clarithromycin. The mechanism of the 

clarithromycin/atazanavir interaction is CYP3A4 

inhibition.  

ANTIFUNGALS 

Ketoconazole 200 mg once daily 

(atazanavir 400 mg once daily)  

No significant effect on atazanavir concentrations 

was observed.  

Ketoconazole and 

itraconazole should 

be used cautiously 

with 

atazanavir/ritonavir. 

High doses of 

ketoconazole and 

itraconazole 

(>200 mg/day) are 

not recommended.  

Itraconazole  Itraconazole, like ketoconazole, is a potent 

inhibitor as well as a substrate of CYP3A4.  

Based on data obtained with other boosted PIs 

and ketoconazole, where ketoconazole AUC 

showed a 3-fold increase, atazanavir/ritonavir is 

expected to increase ketoconazole or itraconazole 

concentrations.  

Voriconazole 200 mg twice daily 

(atazanavir 300 mg/ritonavir 

100 mg once daily)  

Subjects with at least one 

functional CYP2C19 allele. 

Voriconazole AUC ↓33% (↓42% ↓22%)  

Voriconazole Cmax ↓10% (↓22% ↓4%)  

Voriconazole Cmin ↓39% (↓49% ↓28%)  

 

Atazanavir AUC ↓12% (↓18% ↓5%)  

Atazanavir Cmax ↓13% (↓20% ↓4%)  

Atazanavir Cmin ↓ 20 % (↓28 % ↓10%) 

  

Ritonavir AUC ↓12% (↓17% ↓7%)  

Ritonavir Cmax ↓9% (↓17% ↔0%)  

Ritonavir Cmin ↓25% (↓35% ↓14%)  

 

In the majority of patients with at least one 

functional CYP2C19 allele, a reduction in both 

voriconazole and atazanavir exposures are 

expected.  

Co-administration of 

voriconazole and 

atazanavir with 

ritonavir is not 

recommended unless 

an assessment of the 

benefit/risk to the 

patient justifies the 

use of voriconazole 

(see section 4.4).  

At the time 

voriconazole 

treatment is required, 

a patient’s CYP2C19 

genotype should be 

performed if 

feasible.  

Therefore if the 

combination is 

unavoidable, the 

following 

recommendations are 

made according to 

the CYP2C19 status:  

- in patients with at 

least one functional 

CYP2C19 allele, 

close clinical 

Voriconazole 50 mg twice daily 

(atazanavir 300 mg/ritonavir 

100 mg once daily)  

Subjects without a functional 

CYP2C19 allele.  

Voriconazole AUC ↑561% (↑451% ↑699%)  

Voriconazole Cmax ↑438% (↑355% ↑539%)  

Voriconazole Cmin ↑765% (↑571% ↑1,020%)  

 

Atazanavir AUC ↓20% (↓35% ↓3%)  

Atazanavir Cmax ↓19% (↓34% ↔0.2%)  



16 

Atazanavir Cmin ↓ 31 % (↓46 % ↓13%) 

  

Ritonavir AUC ↓11% (↓20% ↓1%)  

Ritonavir Cmax ↓11% (↓24% ↑4%)  

Ritonavir Cmin ↓19% (↓35% ↑1%)  

 

In a small number of patients without a 

functional CYP2C19 allele, significantly 

increased voriconazole exposures are expected.  

monitoring for a loss 

of both voriconazole 

(clinical signs) and 

atazanavir (virologic 

response) efficacy is 

recommended.  

- in patients without 

a functional 

CYP2C19 allele, 

close clinical and 

laboratory 

monitoring of 

voriconazole-

associated adverse 

events is 

recommended  

If genotyping is not 

feasible, full 

monitoring of safety 

and efficacy should 

be performed.  

Fluconazole 200 mg once daily  

(atazanavir 300 mg and ritonavir 

100 mg once daily)  

Atazanavir and fluconazole concentrations were 

not significantly modified when Atazanavir 

/ritonavir was co-administered with fluconazole.  

No dosage 

adjustments are 

needed for 

fluconazole and 

atazanavir.  

ANTIMYCOBACTERIAL 

Rifabutin 150 mg twice weekly  

(atazanavir 300 mg and ritonavir 

100 mg once daily)  

Rifabutin AUC ↑48% (↑19% ↑84%) **  

Rifabutin Cmax ↑149% (↑103% ↑206%) **  

Rifabutin Cmin ↑40% (↑5% ↑87%) ** 

  

25-O-desacetyl-rifabutin AUC ↑990% (↑714% 

↑1361%) **  

25-O-desacetyl-rifabutin Cmax ↑677% (↑513% 

↑883%) **  

25-O-desacetyl-rifabutin Cmin ↑1045% (↑715% 

↑1510%) ** 

  

** When compared to rifabutin 150 mg once 

daily alone. Total rifabutin and 25-O-desacetyl-

rifabutin AUC ↑119% (↑78% ↑169%).  

In previous studies, the pharmacokinetics of 

atazanavir was not altered by rifabutin.  

When given with 

atazanavir, the 

recommended dose 

of rifabutin is 

150 mg 3 times per 

week on set days (for 

example Monday-

Wednesday-Friday). 

Increased monitoring 

for rifabutin-

associated adverse 

reactions including 

neutropenia and 

uveitis is warranted 

due to an expected 

increase in exposure 

to rifabutin. Further 

dosage reduction of 

rifabutin to 150 mg 

twice weekly on set 

days is 

recommended for 

patients in whom the 

150 mg dose 3 times 

per week is not 

tolerated. It should 



17 

be kept in mind that 

the twice weekly 

dosage of 150 mg 

may not provide an 

optimal exposure to 

rifabutin thus leading 

to a risk of rifamycin 

resistance and a 

treatment failure. No 

dose adjustment is 

needed for 

atazanavir.  

Rifampicin  Rifampicin is a strong CYP3A4 inducer and has 

been shown to cause a 72% decrease in 

atazanavir AUC which can result in virological 

failure and resistance development. During 

attempts to overcome the decreased exposure by 

increasing the dose of atazanavir or other 

protease inhibitors with ritonavir, a high 

frequency of liver reactions was seen.  

The combination of 

rifampicin and 

atazanavir is 

contraindicated (see 

section 4.3).  

ANTIPSYCHOTICS 

Quetiapine Due to CYP3A4 inhibition by atazanavir, 

concentrations of quetiapine are expected to 

increase. 

Co-administration of 

quetiapine with 

atazanavir is 

contraindicated as 

atazanavir may 

increase quetiapine-

related toxicity. 

Increased plasma 

concentrations of 

quetiapine may lead 

to coma (see section 

4.3). 

Lurasidone Atazanavir is expected to increase plasma levels 

of lurasidone due to CYP3A4 inhibition. 

Co-administration of 

lurasidone with 

atazanavir is contra-

indicated as this may 

increase lurasidone-

related toxicity 

(see section 4.3). 

ACID REDUCING AGENTS 

H2-Receptor antagonists  

Without tenofovir  

In HIV-infected patients with atazanavir/ritonavir at the recommended dose 

300/100 mg once daily 

For patients not 

taking tenofovir, if 

atazanavir 

300 mg/ritonavir 

100 mg and 

H2-receptor 

antagonists are 

co-administered, a 

dose equivalent to 

famotidine 20 mg 

Famotidine 20 mg twice daily  Atazanavir AUC ↓18% (↓25% ↑1%)  

Atazanavir Cmax ↓20% (↓32% ↓7%)  

Atazanavir Cmin ↔1% (↓16% ↑18%)  

Famotidine 40 mg twice daily  Atazanavir AUC ↓23% (↓32% ↓14%)  



18 

Atazanavir Cmax ↓23% (↓33% ↓12%)  

Atazanavir Cmin ↓20% (↓31% ↓8%)  

twice daily should 

not be exceeded. If a 

higher dose of an H2-

receptor antagonist is 

required (e.g., 

famotidine 40 mg 

twice daily or 

equivalent) an 

increase of the 

atazanavir/ritonavir 

dose from 

300/100 mg to 

400/100 mg can be 

considered. 

In Healthy volunteers with atazanavir/ritonavir at an increased dose of 400/100 mg 

once daily  

Famotidine 40 mg twice daily  Atazanavir AUC ↔3% (↓14% ↑22%)  

Atazanavir Cmax ↔2% (↓13% ↑8%)  

Atazanavir Cmin ↓14% (↓32% ↑8%)  

With tenofovir disoproxil fumarate 300 mg once daily (equivalent to 245 mg tenofovir disoproxil) 

In HIV-infected patients with atazanavir/ritonavir at the recommended dose of 

300/100 mg once daily  

For patients who 

are taking tenofovir 

disoproxil 

fumarate,  

If 

atazanavir/ritonavir 

with both tenofovir 

disoproxil fumarate 

and an H2-receptor 

antagonist are 

co-administered, a 

dose increase of 

atazanavir to 400 mg 

with 100 mg of 

ritonavir is 

recommended. A 

dose equivalent to 

famotidine 40 mg 

twice daily should 

not be exceeded.  

Famotidine 20 mg twice daily  Atazanavir AUC ↓21% (↓34% ↓4%) *  

Atazanavir Cmax ↓21% (↓36% ↓4%) *  

Atazanavir Cmin ↓19% (↓37% ↑5%) *  

Famotidine 40 mg twice daily  Atazanavir AUC ↓24% (↓36% ↓11%)*  

Atazanavir Cmax ↓23% (↓36% ↓8%) *  

Atazanavir Cmin ↓25% (↓47% ↑7%) *  

In HIV-infected patients with atazanavir/ritonavir at an increased dose of 400/100 mg 

once daily  

Famotidine 20 mg twice daily Atazanavir AUC ↑18% (↑6.5% ↑30%)*  

Atazanavir Cmax ↑18% (↑6.7% ↑31%)*  

Atazanavir Cmin ↑24 % (↑10% ↑39%)*  

Famotidine 40 mg twice daily Atazanavir AUC ↔2.3% (↓13% ↑10%)*  

Atazanavir Cmax ↔5% (↓17% ↑8.4%)*  

Atazanavir Cmin ↔1.3% (↓10% ↑15)*  

* When compared to atazanavir 300 mg once 

daily with ritonavir 100 mg once daily and 

tenofovir disoproxil fumarate 300 mg all as a 

single dose with food. When compared to 

atazanavir 300 mg with ritonavir 100 mg without 

tenofovir disoproxil fumarate, atazanavir 

concentrations are expected to be additionally 

decreased by about 20%.  

The mechanism of interaction is decreased 

solubility of atazanavir as intra-gastric pH 

increases with H2-blockers.  

Proton pump inhibitors 



19 

Omeprazole 40 mg once daily  

(atazanavir 400 mg once daily 

with ritonavir 100 mg once daily)  

Atazanavir (am): 2 hr after omeprazole  

Atazanavir AUC ↓61% (↓65% ↓55%)  

Atazanavir Cmax ↓66% (↓62% ↓49%)  

Atazanavir Cmin ↓65% (↓71% ↓59%)  

Co-administration of 

atazanavir with 

ritonavir and proton 

pump inhibitors is 

not recommended. If 

the combination is 

judged unavoidable, 

close clinical 

monitoring is 

recommended in 

combination with an 

increase in the dose 

of atazanavir to 

400 mg with 100 mg 

of ritonavir; doses of 

proton pump 

inhibitors 

comparable to 

omeprazole 20 mg 

should not be 

exceeded (see 

section 4.4).  

Omeprazole 20 mg once daily  

(atazanavir 400 mg once daily 

with ritonavir 100 mg once daily)  

Atazanavir (am): 1 hr after omeprazole  

Atazanavir AUC ↓30% (↓43% ↓14%) *  

Atazanavir Cmax ↓31% (↓42% ↓17%) *  

Atazanavir Cmin ↓31% (↓46% ↓12%) *  

* When compared to atazanavir 300 mg once 

daily with ritonavir 100 mg once daily.  

The decrease in AUC, Cmax, and Cmin was not 

mitigated when an increased dose of atazanavir 

/ritonavir (400/100 mg once daily) was 

temporally separated from omeprazole by 12 

hours. Although not studied, similar results are 

expected with other proton pump inhibitors. This 

decrease in atazanavir exposure might negatively 

impact the efficacy of atazanavir. The mechanism 

of interaction is decreased solubility of atazanavir 

as intra-gastric pH increases with proton pump 

inhibitors.  

Antacids 

Antacids and medicinal 

products containing buffers 

Reduced plasma concentrations of atazanavir 

may be the consequence of increased gastric pH 

if antacids, including buffered medicinal 

products, are administered with atazanavir.  

Atazanavir should be 

administered 2 hours 

before or 1 hour after 

antacids or buffered 

medicinal products.  

ALPHA 1-ADRENORECEPTOR ANTAGONIST 

Alfuzosin Potential for increased alfuzosin concentrations 

which can result in hypotension. The mechanism 

of interaction is CYP3A4 inhibition by atazanavir 

and/or ritonavir.  

Co-administration of 

alfuzosin with 

atazanavir is 

contraindicated (see 

section 4.3)  

ANTICOAGULANTS 

Warfarin Co-administration with atazanavir has the 

potential to increase or decrease warfarin 

concentrations. 

It is recommended 

that the International 

Normalised Ratio 

(INR) be monitored 

carefully during 

treatment with 

atazanavir, 

especially when 

commencing 

therapy.  

ANTIEPILEPTICS 



20 

Carbamazepine Atazanavir may increase plasma levels of 

carbamazepine due to CYP3A4 inhibition.  

Due to carbamazepine inducing effect, a 

reduction in atazanavir exposure cannot be ruled 

out. 

Carbamazepine 

should be used with 

caution in 

combination with 

atazanavir. If 

necessary, monitor 

carbamazepine 

serum concentrations 

and adjust the dose 

accordingly. Close 

monitoring of the 

patient's virologic 

response should be 

excercised.  

Phenytoin, phenobarbital Ritonavir may decrease plasma levels of 

phenytoin and/or phenobarbital due to CYP2C9 

and CYP2C19 induction. Due to 

phenytoin/phenobarbital inducing effect, a 

reduction in atazanavir exposure cannot be ruled 

out 

Phenobarbital and 

phenytoin should be 

used with caution in 

combination with 

atazanavir /ritonavir.  

When 

atazanavir/ritonavir 

is co-administered 

with either phenytoin 

or phenobarbital, a 

dose adjustment of 

phenytoin or 

phenobarbital may 

be required.  

Close monitoring of 

patient’s virologic 

response should be 

exercised.  

Lamotrigine Co-administration of lamotrigine and 

atazanavir/ritonavir may decrease lamotrigine 

plasma concentrations due to UGT1A4 induction. 

Lamotrigine should 

be used with caution 

in combination with 

atazanavir/ritonavir.  

If necessary, monitor 

lamotrigine 

concentrations and 

adjust the dose 

accordingly.  

ANTINEOPLASTICS AND IMMUNOSUPRESSANTS 

Antineoplastics  

Irinotecan Atazanavir inhibits UGT and may interfere with 

the metabolism of irinotecan, resulting in 

increased irinotecan toxicities.  

If atazanavir is 

co-administered with 

irinotecan, patients 

should be closely 

monitored for 

adverse events 

related to irinotecan.  

Immunosuppressants  



21 

Cyclosporin  

Tacrolimus  

Sirolimus  

Concentrations of these immunosuppressants 

may be increased when co-administered with 

atazanavir due to CYP3A4 inhibition.  

More frequent 

therapeutic 

concentration 

monitoring of these 

medicinal products is 

recommended until 

plasma levels have 

been stabilised.  

CARDIOVASCULAR AGENTS 

Antiarrhythmics  

Amiodarone, Systemic lidocaine, 

Quinidine 

Concentrations of these antiarrhythmics may be 

increased when co-administered with atazanavir. 

The mechanism of amiodarone or systemic 

lidocaine/atazanavir interaction is CYP3A 

inhibition. Quinidine has a narrow therapeutic 

window and is contraindicated due to potential 

inhibition of CYP3A by atazanavir.  

Caution is warranted 

and therapeutic 

concentration 

monitoring is 

recommended when 

available. The 

concomitant use of 

quinidine is 

contraindicated (see 

section 4.3).  

Calcium channel blockers  

Bepridil Atazanavir should not be used in combination 

with medicinal products that are substrates of 

CYP3A4 and have a narrow therapeutic index.  

Co-administration 

with bepridil is 

contraindicated (see 

section 4.3)  

Diltiazem 180 mg once daily  

(atazanavir 400 mg once daily)  

Diltiazem AUC ↑125% (↑109% ↑141%)  

Diltiazem Cmax ↑98% (↑78% ↑119%)  

Diltiazem Cmin ↑142% (↑114% ↑173%)  

Desacetyl-diltiazem AUC ↑165% (↑145% 

↑187%)  

Desacetyl-diltiazem Cmax ↑172% (↑144% ↑203%)  

Desacetyl-diltiazem Cmin ↑121% (↑102% ↑142%)  

No significant effect on atazanavir concentrations 

was observed. There was an increase in the 

maximum PR interval compared to atazanavir 

alone. Co-administration of diltiazem and 

atazanavir /ritonavir has not been studied. The 

mechanism of diltiazem/atazanavir interaction is 

CYP3A4 inhibition.  

An initial dose 

reduction of 

diltiazem by 50% is 

recommended, with 

subsequent titration 

as needed and ECG 

monitoring.  

Verapamil Serum concentrations of verapamil may be 

increased by atazanavir due to CYP3A4 

inhibition.  

Caution should be 

exercised when 

verapamil is 

co-administered with 

atazanavir.  

CORTICOSTEROIDS 



22 

Fluticasone propionate 

intranasal 50 µg 4 times daily 

for 7 days  

(ritonavir 100 mg capsules twice 

daily)  

The fluticasone propionate plasma levels 

increased significantly, whereas the intrinsic 

cortisol levels decreased by approximately 86% 

(90% confidence interval 82%- 89%). Greater 

effects may be expected when fluticasone 

propionate is inhaled. Systemic corticosteroid 

effects including Cushing's syndrome and adrenal 

suppression have been reported in patients 

receiving ritonavir and inhaled or intranasally 

administered fluticasone propionate; this could 

also occur with other corticosteroids metabolised 

via the P450 3A pathway, e.g., budesonide. The 

effects of high fluticasone systemic exposure on 

ritonavir plasma levels are yet unknown. The 

mechanism of interaction is CYP3A4 inhibition.  

Co- administration 

of atazanavir 

/ritonavir and these 

glucocorticoids is 

not recommended 

unless the potential 

benefit of treatment 

outweighs the risk of 

systemic 

corticosteroid effects 

(see section 4.4). A 

dose reduction of the 

glucocorticoid 

should be considered 

with close 

monitoring of local 

and systemic effects 

or a switch to a 

glucocorticoid, 

which is not a 

substrate for 

CYP3A4 (e.g., 

beclomethasone). 

Moreover, in case of 

withdrawal of 

glucocorticoids, 

progressive dose 

reduction may have 

to be performed over 

a longer period.  

ERECTILE DYSFUNCTION 

PDE5 Inhibitors 

Sildenafil, tadalafil, vardenafil Sildenafil, tadalafil, and vardenafil are 

metabolised by CYP3A4. Co-administration with 

atazanavir may result in increased concentrations 

of the PDE5 inhibitor and an increase in 

PDE5-associated adverse events, including 

hypotension, visual changes, and priapism. The 

mechanism of this interaction is CYP3A4 

inhibition.  

Patients should be 

warned about these 

possible side effects 

when using PDE5 

inhibitors for erectile 

dysfunction with 

atazanavir (see 

section 4.4).  

Also see 

PULMONARY 

ARTERIAL 

HYPERTENSION in 

this table for further 

information 

regarding co-

administration of 

atazanavir with 

sildenafil.  

HERBAL PRODUCTS 

St. John’s wort (Hypericum 

perforatum) 

Concomitant use of St. John’s wort with 

atazanavir may be expected to result in 

significant reduction in plasma levels of 

Co-administration of 

atazanavir with 

products containing 



23 

atazanavir. This effect may be due to an 

induction of CYP3A4. There is a risk of loss of 

therapeutic effect and development of resistance 

(see section 4.3).  

St. John’s wort is 

contraindicated.  

HORMONAL CONTRACEPTIVES 

Ethinyloestradiol 25 μg + 

norgestimate  

(atazanavir 300 mg once daily 

with ritonavir 100 mg once daily)  

Ethinyloestradiol AUC ↓19% (↓25% ↓13%)  

Ethinyloestradiol Cmax ↓16% (↓26% ↓5%)  

Ethinyloestradiol Cmin ↓37% (↓45% ↓29%)  

Norgestimate AUC ↑85% (↑67% ↑105%)  

Norgestimate Cmax ↑68% (↑51% ↑88%)  

Norgestimate Cmin ↑102% (↑77% ↑131%)  

While the concentration of ethinyloestradiol was 

increased with atazanavir given alone, due to 

both UGT and CYP3A4 inhibition by atazanavir, 

the net effect of atazanavir/ritonavir is a decrease 

in ethinyloestradiol levels because of the 

inducing effect of ritonavir.  

The increase in progestin exposure may lead to 

related side-effects (e.g. insulin resistance, 

dyslipidemia, acne and spotting), thus possibly 

affecting the compliance.  

If an oral 

contraceptive is 

administered with 

atazanavir /ritonavir, 

it is recommended 

that the oral 

contraceptive contain 

at least 30 μg of 

ethinyloestradiol and 

that the patient be 

reminded of strict 

compliance with this 

contraceptive dosing 

regimen. Co-

administration of 

atazanavir /ritonavir 

with other hormonal 

contraceptives or 

oral contraceptives 

containing 

progestogens other 

than norgestimate 

has not been studied, 

and therefore should 

be avoided. An 

alternate reliable 

method of 

contraception is 

recommended.  

Ethinyloestradiol 35 µg + 

norethindrone 

(atazanavir 400 mg once daily) 

Ethinyloestradiol AUC ↑48% (↑31% ↑68%) 

Ethinyloestradiol Cmax ↑15% (↓1% ↑32%) 

Ethinyloestradiol Cmin ↑91% (↑57% ↑133%) 

Norethindrone AUC ↑110% (↑68% ↑162%) 

Norethindrone Cmax ↑67% (↑42% ↑196%) 

Norethindrone Cmin ↑262% (↑157% ↑409%) 

The increase in progestin exposure may lead to 

related side-effects (e.g. insulin resistance, 

dyslipidemia, acne and spotting), thus possibly 

affecting the compliance. 

LIPID LOWERING AGENTS 

HMG- CoA reductase inhibitors  

Simvastatin  

Lovastatin 

Simvastatin and lovastatin are highly dependent 

on CYP3A4 for their metabolism and 

co-administration with atazanavir may result in 

increased concentrations.  

Co-administration of 

simvastatin or 

lovastatin with 

atazanavir is 

contraindicated due 

to an increased risk 

of myopathy 



24 

including 

rhabdomyolysis (see 

section 4.3).  

Atorvastatin The risk of myopathy including rhabdomyolysis 

may also be increased with atorvastatin, which is 

also metabolised by CYP3A4.  

Co-administration of 

atorvastatin with 

atazanavir is not 

recommended. If the 

use of atorvastatin is 

considered strictly 

necessary, the lowest 

possible dose of 

atorvastatin should 

be administered with 

careful safety 

monitoring (see 

section 4.4).  

Pravastatin  

Fluvastatin 

Although not studied, there is a potential for an 

increase in pravastatin or fluvastatin exposure 

when co-administered with protease inhibitors. 

Pravastatin is not metabolised by CYP3A4. 

Fluvastatin is partially metabolised by CYP2C9.  

Caution should be 

exercised.  

INHALED BETA AGONISTS 

Salmeterol Co-administration with atazanavir may result in 

increased concentrations of salmeterol and an 

increase in salmeterol- associated adverse events.  

The mechanism of interaction is CYP3A4 

inhibition by atazanavir and/or ritonavir.  

Co-administration of 

salmeterol with 

atazanavir is not 

recommended (see 

section 4.4).  

OPIOIDS 

Buprenorphine, once daily, 

stable maintenance dose  

(atazanavir 300 mg once daily 

with ritonavir 100 mg once daily)  

Buprenorphine AUC ↑67%  

Buprenorphine Cmax ↑37%  

Buprenorphine Cmin ↑69%  

 

Norbuprenorphine AUC ↑105%  

Norbuprenorphine Cmax ↑61%  

Norbuprenorphine Cmin ↑101%  

 

The mechanism of interaction is CYP3A4 and 

UGT1A1 inhibition.  

Concentrations of atazanavir (when given with 

ritonavir) were not significantly affected.  

Co-administration 

with atazanavir with 

ritonavir warrants 

clinical monitoring 

for sedation and 

cognitive effects. A 

dose reduction of 

buprenorphine may 

be considered  

Methadone, stable maintenance 

dose  

(atazanavir 400 mg once daily)  

No significant effect on methadone 

concentrations was observed. Given that low 

dose ritonavir (100 mg twice daily) has been 

shown to have no significant effect on methadone 

concentrations, no interaction is expected if 

methadone is co-administered with atazanavir, 

based on these data.  

No dosage 

adjustment is 

necessary if 

methadone is 

co-administered with 

atazanavir.  

PULMONARY ARTERIAL HYPERTENSION 



25 

PDE5 Inhibitors 

Sildenafil Co-administration with atazanavir may result in 

increased concentrations of the PDE5 inhibitor 

and an increase in PDE5-inhibitor-associated 

adverse events.  

The mechanism of interaction is CYP3A4 

inhibition by atazanavir and/or ritonavir.  

A safe and effective 

dose in combination 

with atazanavir has 

not been established 

for sildenafil when 

used to treat 

pulmonary arterial 

hypertension. 

Sildenafil, when 

used for the 

treatment of 

pulmonary arterial 

hypertension, is 

contraindicated (see 

section 4.3).  

SEDATIVES 

Benzodiazepines  

Midazolam  

Triazolam  

Midazolam and triazolam are extensively 

metabolised by CYP3A4. Co-administration with 

atazanavir may cause a large increase in the 

concentration of these benzodiazepines. No drug 

interaction study has been performed for the co-

administration of atazanavir with 

benzodiazepines. Based on data for other 

CYP3A4 inhibitors, plasma concentrations of 

midazolam are expected to be significantly 

higher when midazolam is given orally. Data 

from concomitant use of parenteral midazolam 

with other protease inhibitors suggest a possible 

3-4 fold increase in midazolam plasma levels.  

Co-administration of 

atazanavir with 

triazolam or orally 

administered 

midazolam is 

contraindicated (see 

section 4.3), whereas 

caution should be 

used with co-

administration of 

atazanavir and 

parenteral 

midazolam. If 

atazanavir is co-

administered with 

parenteral 

midazolam, it should 

be done in an 

intensive care unit 

(ICU) or similar 

setting which 

ensures close clinical 

monitoring and 

appropriate medical 

management in case 

of respiratory 

depression and/or 

prolonged sedation. 

Dosage adjustment 

for midazolam 

should be 

considered, 

especially if more 

than a single dose of 

midazolam is 

administered.  

 



26 

In case of withdrawal of ritonavir from the recommended atazanavir-boosted regimen (see section 4.4) 

 

The same recommendations for drug drug interactions would apply except: 

• that co-administration is not recommended with tenofovir, boceprevir, carbamazepine, phenytoin, 

phenobarbital, proton pump inhibitors, and buprenorphine. 

• that co-administration with famotidine is not recommended but if required, atazanavir without ritonavir 

should be administered either 2 hours after famotidine or 12 hours before. No single dose of famotidine 

should exceed 20 mg, and the total daily dose of famotidine should not exceed 40 mg. 

• the need to consider that 

- co-administration of voriconazole and atazanavir without ritonavir may affect atazanavir 

concentrations 

- co-administration of fluticasone and atazanavir without ritonavir may increase fluticasone 

concentrations relative to fluticasone given alone 

- if an oral contraceptive is administered with atazanavir without ritonavir, it is recommended that the 

oral contraceptive contain no more than 30 µg of ethinyloestradiol 

- no dose adjustment of lamotrigine is required 

 

Paediatric population 

 

Interaction studies have only been performed in adults. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

A moderate amount of data in pregnant women (between 300-1000 pregnancy outcomes) indicate no 

malformative toxicity of atazanavir. Animal studies do not indicate reproductive toxicity (see section 5.3). 

The use of Atazanavir Mylan with ritonavir may be considered during pregnancy only if the potential benefit 

justifies the potential risk.  

 

In clinical trial AI424-182 atazanavir/ritonavir (300/100 mg or 400/100 mg) in combination with 

zidovudine/lamivudine was administered to 41 pregnant women during the second or third trimester. Six of 

20 (30%) women on atazanavir/ritonavir 300/100 mg and 13 of 21 (62%) women on atazanavir /ritonavir 

400/100 mg experienced grades 3 to 4 hyperbilirubinaemia. There were no cases of lactic acidosis observed 

in the clinical trial AI424-182.  

 

The study assessed 40 infants who received antiretroviral prophylactic treatment (which did not include 

atazanavir) and were negative for HIV-1 DNA at the time of delivery and/or during the first 6 months 

postpartum. Three of 20 infants (15%) born to women treated with atazanavir/ritonavir 300/100 mg and four 

of 20 infants (20%) born to women treated with atazanavir/ritonavir 400/100 mg experienced grade 3-4 

bilirubin. There was no evidence of pathologic jaundice and six of 40 infants in this study received 

phototherapy for a maximum of 4 days. There were no reported cases of kernicterus in neonates.  

 

For dosing recommendations see section 4.2 and for pharmacokinetic data see section 5.2.  

 

It is not known whether Atazanavir Mylan with ritonavir administered to the mother during pregnancy will 

exacerbate physiological hyperbilirubinaemia and lead to kernicterus in neonates and infants. In the 

prepartum period, additional monitoring should be considered. 

 

Breast-feeding 

 

Atazanavir has been detected in human milk. As a general rule, it is recommended that HIV infected women 

not breast-feed their infants in order to avoid transmission of HIV. 

 

Fertility 



27 

 

In a nonclinical fertility and early embryonic development study in rats, atazanavir altered oestrus cycling 

with no effects on mating or fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Patients should be informed that dizziness has been reported during treatment with regimens containing 

atazanavir (see section 4.8). 

 

4.8 Undesirable effects 

 

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%. In the majority of cases, jaundice was reported within a few days to a few months after 

the initiation of treatment (see section 4.4).  

 

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. Regular monitoring of the renal 

function of patients should be maintained throughout the treatment duration (see section 4.4).  

 

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.  

 

Immune system disorders: uncommon: hypersensitivity  

Metabolism and nutrition disorders: uncommon: weight decreased, weight gain, anorexia, appetite 

increased  

Psychiatric disorders: uncommon: depression, disorientation, anxiety, insomnia, sleep 

disorder, abnormal dream  

Nervous system disorders: common: headache;  

uncommon: peripheral neuropathy, syncope, amnesia, dizziness, 

somnolence, dysgeusia  

Eye disorders: common: ocular icterus  

Cardiac disorders: uncommon: torsades de pointesa  

rare: QTc prolongationa, oedema, palpitation  



28 

Vascular disorders: uncommon: hypertension  

Respiratory, thoracic and mediastinal 

disorders:  

uncommon: dyspnoea  

Gastrointestinal disorders: common: vomiting, diarrhoea, abdominal pain, nausea, 

dyspepsia;  

uncommon: pancreatitis, gastritis, abdominal distension, 

stomatitis aphthous, flatulence, dry mouth  

Hepatobiliary disorders: common: jaundice;  

uncommon: hepatitis, cholelithiasisa, cholestasisa;  

rare: hepatosplenomegaly, cholecystitisa  

Skin and subcutaneous tissue disorders: common: rash;  

uncommon: erythemia multiformea,b, toxic skin eruptionsa,b, 

drug rash with eosinophilia and systemic symptoms (DRESS) 

syndromea,b, angioedemaa, urticaria, alopecia, pruritus;  

rare: Stevens-Johnson syndromea,b, vesiculobullous rash, 

eczema, vasodilatation  

Musculoskeletal and connective tissue 

disorders: 

uncommon: muscle atrophy, arthralgia, myalgia;  

rare: myopathy  

Renal and urinary disorders: uncommon: nephrolithiasisa, haematuria, proteinuria, 

pollakiuria, interstitial nephritis, chronic kidney diseasea;  

rare: kidney pain  

Reproductive system and breast disorders:  uncommon: gynaecomastia  

General disorders and administration site 

conditions: 

common: fatigue;  

uncommon: chest pain, malaise, pyrexia, asthenia;  

rare: gait disturbance  
a These adverse reactions were identified through post-marketing surveillance, however, the frequencies were estimated from a 

statistical calculation based on the total number of patients exposed to atazanavir in randomised controlled and other available 

clinical trials (n = 2321).  
b See description of selected adverse reactions for more details.  

 

Description of selected adverse reactions 

 

In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral 

therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. 

Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported; 

however, the reported time to onset is more variable and these events can occur many months after initiation 

of treatment (see section 4.4).  

 

Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, 

advanced HIV disease or long- term exposure to combination antiretroviral therapy (CART). The frequency 

of this is unknown (see section 4.4).  

 

Metabolic parameters 

Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 4.4).  

 

Rash and associated syndromes  

Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 3 weeks of 

starting therapy with atazanavir.  

 

Stevens-Johnson syndrome (SJS), erythema multiforme, toxic skin eruptions and drug rash with eosinophilia 

and systemic symptoms (DRESS) syndrome have been reported with the use of atazanavir (see section 4.4).  

 

Laboratory abnormalities 



29 

The most frequently reported laboratory abnormality in patients receiving regimens containing atazanavir 

and one or more NRTIs was elevated total bilirubin reported predominantly as elevated indirect 

[unconjugated] bilirubin (87% Grade 1, 2, 3, or 4). Grade 3 or 4 elevation of total bilirubin was noted in 37% 

(6% Grade 4). Among experienced patients treated with atazanavir 300 mg once daily with 100 mg ritonavir 

once daily for a median duration of 95 weeks, 53% had Grade 3-4 total bilirubin elevations. Among naive 

patients treated with atazanavir 300 mg once daily with 100 mg ritonavir once daily for a median duration of 

96 weeks, 48% had Grade 3-4 total bilirubin elevations (see section 4.4).  

 

Other marked clinical laboratory abnormalities (Grade 3 or 4) reported in ≥ 2% of patients receiving 

regimens containing atazanavir and one or more NRTIs included: elevated creatine kinase (7%), elevated 

alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) (5%), low neutrophils (5%), 

elevated aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) (3%), and 

elevated lipase (3%).  

 

Two percent of patients treated with atazanavir experienced concurrent Grade 3-4 ALT/AST and Grade 3-4 

total bilirubin elevations.  

 

Paediatric population 

 

In clinical study AI424-020, paediatric patients 3 months to less than 18 years of age who received either the 

oral powder or capsule formulation had a mean duration of treatment with atazanavir of 115 weeks. The 

safety profile in this study was overall comparable to that seen in adults. Both asymptomatic first-degree 

(23%) and second-degree (1%) atrioventricular block were reported in paediatric patients. The most 

frequently reported laboratory abnormality in paediatric patients receiving atazanavir was elevation of total 

bilirubin (≥ 2.6 times ULN, Grade 3-4) which occurred in 45% of patients.  

 

In clinical studies AI424-397 and AI424-451, paediatric patients 3 months to less than 11 years of age had a 

mean duration of treatment with atazanavir oral powder of 80 weeks. No deaths were reported. The safety 

profile in these studies was overall comparable to that seen in previous paediatric and adult studies. The most 

frequently reported laboratory abnormalities in paediatric patients receiving atazanavir oral powder was 

elevation of total bilirubin (≥ 2.6 times ULN, Grade 3-4; 16%) and increased amylase (Grade 3-4; 33%), 

generally of non-pancreatic origin. Elevation in ALT levels were more frequently reported in paediatric 

patients in these studies than in adults. 

 

Other special populations 

 

Patients co-infected with hepatitis B and/or hepatitis C virus 

Among 1,151 patients receiving atazanavir 400 mg once daily, 177 patients were co-infected with chronic 

hepatitis B or C, and among 655 patients receiving atazanavir 300 mg once daily with ritonavir 100 mg once 

daily, 97 patients were co-infected with chronic hepatitis B or C. Co-infected patients were more likely to 

have baseline hepatic transaminase elevations than those without chronic viral hepatitis. No differences in 

frequency of bilirubin elevations were observed between these patients and those without viral hepatitis. The 

frequency of treatment emergent hepatitis or transaminase elevations in co-infected patients was comparable 

between atazanavir and comparator regimens (see section 4.4).  

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 

to report any suspected adverse reactions via the national reporting system listed in Appendix V. 

 

4.9 Overdose 

 

Human experience of acute overdose with atazanavir is limited. Single doses up to 1,200 mg have been taken 

by healthy volunteers without symptomatic untoward effects. At high doses that lead to high drug exposures, 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


30 

jaundice due to indirect (unconjugated) hyperbilirubinaemia (without associated liver function test changes) 

or PR interval prolongations may be observed (see sections 4.4 and 4.8).  

 

Treatment of overdose with atazanavir should consist of general supportive measures, including monitoring 

of vital signs and electrocardiogram (ECG), and observations of the patient’s clinical status. If indicated, 

elimination of unabsorbed atazanavir should be achieved by emesis or gastric lavage. Administration of 

activated charcoal may also be used to aid removal of unabsorbed drug. There is no specific antidote for 

overdose with atazanavir. Since atazanavir is extensively metabolised by the liver and is highly protein 

bound, dialysis is unlikely to be beneficial in significant removal of this medicinal product. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antivirals for systemic use, protease inhibitors, ATC code: J05AE08  

 

Mechanism of action 

 

Atazanavir is an azapeptide HIV-1 protease inhibitor (PI). The compound selectively inhibits the virus-

specific processing of viral Gag-Pol proteins in HIV- 1 infected cells, thus preventing formation of mature 

virions and infection of other cells.  

 

Antiviral activity in vitro 

 

Atazanavir exhibits anti- HIV-1 (including all clades tested) and anti-HIV-2 activity in cell culture.  

 

Resistance 

Antiretroviral treatment naive adult patients 

In clinical trials of antiretroviral treatment naive patients treated with unboosted atazanavir, the I50L 

substitution, sometimes in combination with an A71V change, is the signature resistance substitution for 

atazanavir. Resistance levels to atazanavir ranged from 3.5- to 29-fold without evidence of phenotypic cross 

resistance to other PIs. In clinical trials of antiretroviral treatment naive patients treated with boosted 

atazanavir, the I50L substitution did not emerge in any patient without baseline PI substitutions. The N88S 

substitution has been rarely observed in patients with virologic failure on atazanavir (with or without 

ritonavir). While it may contribute to decreased susceptibility to atazanavir when it occurs with other 

protease substitutions, in clinical studies N88S by itself does not always lead to phenotypic resistance to 

atazanavir or have a consistent impact on clinical efficacy.  

 

Table 3.  De novo substitutions in treatment naive patients failing therapy with atazanavir + 

ritonavir (Study 138, 96 weeks) 

Frequency de novo PI substitution (n=26)a 

>20%  none  

10-20%  none  
a Number of patients with paired genotypes classified as virological failures (HIV RNA ≥ 400 copies/ml).  

 

The M184I/V substitution emerged in 5/26 Atazanavir /ritonavir and 7/26 lopinavir/ritonavir virologic 

failure patients, respectively.  

 

Antiretroviral treatment experienced adult patients 

In antiretroviral treatment experienced patients from Studies 009, 043, and 045, 100 isolates from patients 

designated as virological failures on therapy that included either atazanavir, atazanavir + ritonavir, or 

atazanavir + saquinavir were determined to have developed resistance to atazanavir. Of the 60 isolates from 



31 

patients treated with either atazanavir or atazanavir + ritonavir, 18 (30%) displayed the I50L phenotype 

previously described in naive patients.  

 

Table 4.  De novo substitutions in treatment experienced patients failing therapy with atazanavir + 

ritonavir (Study 045, 48 weeks) 

Frequency de novo PI substitution (n=35)a,b 

>20%  M36, M46, I54, A71, V82  

10-20%  L10, I15, K20, V32, E35, S37, F53, I62, G73, I84, L90  
a Number of patients with paired genotypes classified as virological failures (HIV RNA ≥ 400 copies/ml).  
b Ten patients had baseline phenotypic resistance to atazanavir + ritonavir (fold change [FC]>5.2). FC 

susceptibility in cell culture relative to the wild-type reference was assayed using PhenoSenseTM (Monogram 

Biosciences, South San Francisco, California, USA)  

 

None of the de novo substitutions (see Table 4) are specific to atazanavir and may reflect re-emergence of 

archived resistance on atazanavir + ritonavir in Study 045 treatment-experienced population.  

 

The resistance in antiretroviral treatment experienced patients mainly occurs by accumulation of the major 

and minor resistance substitutions described previously to be involved in protease inhibitor resistance.  

 

Clinical results 

 

In antiretroviral naive adult patients 

 

Study 138 is an international randomised, open-label, multicenter, prospective trial of treatment naïve 

patients comparing atazanavir/ritonavir (300 mg/100 mg once daily) to lopinavir/ritonavir (400 mg/100 mg 

twice daily), each in combination with fixed dose tenofovir disoproxil fumarate/emtricitabine 

(300 mg/200 mg tablets once daily). The atazanavir/ritonavir arm showed similar (non-inferior) antiviral 

efficacy compared to the lopinavir/ritonavir arm, as assessed by the proportion of patients with HIV RNA < 

50 copies/ml at week 48 (Table 5).  

 

Analyses of data through 96 weeks of treatment demonstrated durability of antiviral activity (Table 5).  

 

Table 5:  Efficacy Outcomes in Study 138 a  

Parameter Atazanavir/ritonavirb  

(300 mg/100 mg once daily)  

n=440 

Lopinavir/ritonavirc  

(400 mg/100 mg twice daily)  

n=443 

  Week 48 Week 96 Week 48 Week 96 

HIV RNA <50 copies/ml, % 

All patientsd 78  74  76  68  

Difference estimate  

[95% CI]d 

Week 48: 1.7% [-3.8%, 7.1%]  

Week 96: 6.1% [0.3%, 12.0%]  

Per protocol analysise 86  

(n=392f)  

91  

(n=352)  

89  

(n=372)  

89  

(n=331)  

Difference estimatee  

[95% CI]  

Week 48: -3% [-7.6%, 1.5%]  

Week 96: 2.2% [-2.3%, 6.7%]  

HIV RNA <50 copies/ml, % by Baseline Characteristicd 

HIV RNA  

<100,000 copies/ml  

   

82 (n=217)  

   

75 (n=217)  

   

81 (n=218)  

   

70 (n=218)  

≥100,000 copies/ml  74 (n=223) 74 (n=223)  72 (n=225)  66 (n=225)  

CD4 count  78 (n=58)  78 (n=58)  63 (n=48)  58 (n=48)  



32 

<50 cells/mm3 

50 to <100 cells/mm3 76 (n=45)  71 (n=45)  69 (n=29)  69 (n=29)  

100 to <200 cells/mm3 75 (n=106)  71 (n=106)  78 (n=134)  70 (n=134)  

≥ 200 cells/mm3 80 (n=222)  76 (n=222)  80 (n=228)  69 (n=228)  

HIV RNA Mean Change from Baseline, log10 copies/ml 

All patients  -3.09 (n=397)  -3.21 (n=360)  -3.13 (n=379)  -3.19 (n=340)  

CD4 Mean Change from Baseline, cells/mm3 

All patients  203 (n=370)  268 (n=336)  219 (n=363)  290 (n=317)  

CD4 Mean Change from Baseline, cells/mm3 by Baseline Characteristic  

HIV RNA  

<100,000 copies/ml  

179 (n=183)  243 (n=163)  194 (n=183)  267 (n=152)  

≥100,000 copies/ml  227 (n=187)  291 (n=173)  245 (n=180)  310 (n=165)  
a Mean baseline CD4 cell count was 214 cells/mm3 (range 2 to 810 cells/mm3) and mean baseline plasma 

HIV-1 RNA was 4.94 log10 copies/ml (range 2.6 to 5.88 log10 copies/ml)  
b Atazanavir/RTV with tenofovir disoproxil fumarate/emtricitabine (fixed dose 300 mg/200 mg tablets once 

daily).  
c Lopinavir/RTV with tenofovir disoproxil fumarate/emtricitabine (fixed dose 300 mg/200 mg tablets once 

daily).  
d Intent-to-treat analysis, with missing values considered as failures.  
e Per protocol analysis: Excluding non-completers and patients with major protocol deviations.  
f Number of patients evaluable.  

 

Data on withdrawal of ritonavir from atazanavir boosted regimen (see also section 4.4) Study 136 

(INDUMA) 

 

In an open-label, randomised, comparative study following a 26- to 30-week induction phase with atazanavir 

300 mg + ritonavir 100 mg once daily and two NRTIs, unboosted atazanavir 400 mg once daily and two 

NRTIs administered during a 48-week maintenance phase (n=87) had similar antiviral efficacy compared 

with atazanavir + ritonavir and two NRTIs (n=85) in HIV infected subjects with fully suppressed HIV 

replication, as assessed by the proportion of subjects with HIV RNA < 50 copies/ml: 78% of subjects on 

unboosted atazanavir and two NRTIs compared with 75% on atazanavir + ritonavir and two NRTIs. 

 

Eleven subjects (13%) in the unboosted atazanavir group and 6 (7%) in the atazanavir + ritonavir group, had 

virologic rebound. Four subjects in the unboosted atazanavir group and 2 in the atazanavir + ritonavir group 

had HIV RNA > 500 copies/ml during the maintenance phase. No subject in either group showed emergence 

of protease inhibitor resistance. The M184V substitution in reverse transcriptase, which confers resistance to 

lamivudine and emtricitabine, was detected in 2 subjects in the unboosted atazanavir and 1 subject in the 

atazanavir + ritonavir group. 

 

There were fewer treatment discontinuations in the unboosted atazanavir group (1 vs. 4 subjects in the 

atazanavir + ritonavir group). There was less hyperbilirubinaemia and jaundice in the unboosted atazanavir 

group compared with the atazanavir + ritonavir group (18 and 28 subjects, respectively). 

 

In antiretroviral experienced adult patients 

 

Study 045 is a randomised, multicenter trial comparing atazanavir /ritonavir (300/100 mg once daily) and 

atazanavir /saquinavir (400/1,200 mg once daily), to lopinavir + ritonavir (400/100 mg fixed dose 

combination twice daily), each in combination with tenofovir disoproxil fumarate (see sections 4.5 and 4.8) 

and one NRTI, in patients with virologic failure on two or more prior regimens containing at least one PI, 

NRTI, and NNRTI. For randomised patients, the mean time of prior antiretroviral exposure was 138 weeks 

for PIs, 281 weeks for NRTIs, and 85 weeks for NNRTIs. At baseline, 34% of patients were receiving a PI 

and 60% were receiving an NNRTI. Fifteen of 120 (13%) patients in the atazanavir + ritonavir treatment arm 



33 

and 17 of 123 (14%) patients in the lopinavir + ritonavir arm had four or more of the PI substitutions L10, 

M46, I54, V82, I84, and L90. Thirty-two percent of patients in the study had a viral strain with fewer than 

two NRTI substitutions.  

 

The primary endpoint was the time-averaged difference in change from baseline in HIV RNA through 48 

weeks (Table 6).  

 

Table 6:  Efficacy Outcomes at Week 48a and at Week 96 (Study 045)  

Parameter ATV/RTVb (300 mg/ 100 mg 

once daily)  

n=120 

LPV/RTVc (400 mg/ 100 mg 

twice daily)  

n=123 

Time-averaged difference 

ATV/RTV-LPV/RTV  

[97.5% CId] 

  Week 48 Week 96 Week 48 Week 96 Week 48 Week 96 

HIV RNA Mean Change from Baseline, log10 copies/ml 

All 

patients  

-1.93  

(n=90 e)  

-2.29  

(n=64)  

-1.87  

(n=99)  

-2.08  

(n=65)  

0.13  

[-0.12, 0.39]  

0.14  

[-0.13, 0.41]  

HIV RNA <50 copies/ml, %f (responder/evaluable) 

All 

patients  

36 (43/120)  32 (38/120)  42 (52/123)  35 (41/118)  NA  NA  

HIV RNA <50 copies/ml by select baseline PI substitutions,f, g % (responder/evaluable) 

0-2  44 (28/63)  41 (26/63)  56 (32/57)  48 (26/54)  NA  NA  

3  18 (2/11)  9 (1/11)  38 (6/16)  33 (5/15)  NA  NA  

≥ 4  27 (12/45)  24 (11/45)  28 (14/50)  20 (10/49)  NA  NA  

CD4 Mean Change from Baseline, cells/mm3 

All 

patients  

110 (n=83)  122 (n=60)  121 (n=94)  154 (n=60)  NA  NA  

a The mean baseline CD4 cell count was 337 cells/mm3 (range: 14 to 1,543 cells/mm3) and the mean baseline 

plasma HIV-1 RNA level was 4.4 log10 copies/ml (range: 2.6 to 5.88 log10 copies/ml).  
b ATV/RTV with tenofovir disoproxil fumarate/emtricitabine (fixed dose 300 mg/200 mg tablets once daily).  
c LPV/RTV with tenofovir disoproxil fumarate/emtricitabine (fixed dose 300 mg/200 mg tablets once daily).  
d Confidence interval.  
e Number of patients evaluable.  
f Intent-to-treat analysis, with missing values considered as failures. Responders on LPV/RTV who 

completed treatment before Week 96 are excluded from Week 96 analysis. The proportion of patients with 

HIV RNA < 400 copies/ml were 53% and 43% for ATV/RTV and 54% and 46% for LPV/RTV at weeks 48 

and 96 respectively.  
g Select substitutions include any change at positions L10, K20, L24, V32, L33, M36, M46, G48, I50, I54, 

L63, A71, G73, V82, I84, and L90 (0-2, 3, 4 or more) at baseline.  

NA = not applicable.  

 

Through 48 weeks of treatment, the mean changes from baseline in HIV RNA levels for atazanavir + 

ritonavir and lopinavir + ritonavir were similar (non-inferior). Consistent results were obtained with the last 

observation carried forward method of analysis (time-averaged difference of 0.11, 97.5% confidence interval 

[-0.15, 0.36]). By as-treated analysis, excluding missing values, the proportions of patients with HIV RNA < 

400 copies/ml (< 50 copies/ml) in the atazanavir + ritonavir arm and the lopinavir + ritonavir arm were 55% 

(40%) and 56% (46%), respectively.  

 

Through 96 weeks of treatment, mean HIV RNA changes from baseline for atazanavir + ritonavir and 

lopinavir + ritonavir met criteria for non-inferiority based on observed cases. Consistent results were 

obtained with the last observation carried forward method of analysis. By as-treated analysis, excluding 

missing values, the proportions of patients with HIV RNA <400 copies/ml (<50 copies/ml) for atazanavir + 



34 

ritonavir were 84% (72%) and for lopinavir + ritonavir were 82% (72%). It is important to note that at time 

of the 96-week analysis, 48 % of patients overall remained on study.  

 

Atazanavir + saquinavir was shown to be inferior to lopinavir + ritonavir.  

 

Paediatric population 

 

Assessment of the pharmacokinetics, safety, tolerability, and efficacy of atazanavir is based on data from the 

open- label, multicenter clinical trial AI424-020 conducted in patients from 3 months to 21 years of age. 

Overall in this study, 182 paediatric patients (81 antiretroviral-naive and 101 antiretroviral-experienced) 

received once daily atazanavir (capsule or powder formulation), with or without ritonavir, in combination 

with two NRTIs.  

 

The clinical data derived from this study are inadequate to support the use of atazanavir (with or without 

ritonavir) in children below 6 years of age.  

 

Efficacy data observed in the 41 paediatric patients aged 6 years to less than 18 years that received 

Atazanavir capsules with ritonavir are presented in Table 7. For treatment-naive paediatric patients, the mean 

baseline CD4 cell count was 344 cells/mm3 (range: 2 to 800 cells/ mm3) and mean baseline plasma HIV 1 

RNA was 4.67 log10 copies/ml (range: 3.70 to 5.00 log10 copies/ml). For treatment-experienced paediatric 

patients, the mean baseline CD4 cell count was 522 cells/mm3 (range: 100 to 1157 cells/ mm3) and mean 

baseline plasma HIV 1 RNA was 4.09 log10 copies/ml (range: 3.28 to 5.00 log10 copies/ml).  

 

Table 7:  Efficacy Outcomes (paediatric patients 6 years to less than 18 years of age) at Week 48 (Study 

AI424-020)  

Parameter Treatment-Naive 

Atazanavir 

Capsules/ritonavir  

(300 mg/100 mg once 

daily)  

n=16 

Treatment-Experienced 

Atazanavir 

Capsules/ritonavir  

(300 mg/100 mg once 

daily)  

n=25 

HIV RNA <50 copies/ml, % a 

All patients  81 (13/16)  24 (6/25)  

HIV RNA <400 copies/ml, % a 

All patients  88 (14/16)  32 (8/25)  

CD4 Mean Change from Baseline, cells/mm3 

All patients  293 (n=14b)  229 (n=14b)  

HIV RNA <50 copies/ml by select baseline PI substitutions,c % (responder/evaluabled) 

0-2  NA  27 (4/15)  

3  NA  -  

≥ 4  NA  0 (0/3)  
a Intent-to-treat analysis, with missing values considered as failures.  
b Number of patients evaluable.  
c PI major L24I, D30N, V32I, L33F, M46IL, I47AV, G48V, I50LV, F53LY,I54ALMSTV, L76V, 

V82AFLST, I84V, N88DS, L90M; PI minor: L10CFIRV, V11I, E35G, K43T, Q58E, A71ILTV, G73ACST, 

T74P, N83D, L89V.  
d Includes patients with baseline resistance data.  

NA = not applicable.  

 

5.2 Pharmacokinetic properties 
 



35 

The pharmacokinetics of atazanavir were evaluated in healthy adult volunteers and in HIV-infected patients; 

significant differences were observed between the two groups. The pharmacokinetics of atazanavir exhibit a 

non-linear disposition.  

 

Absorption 

 

In HIV-infected patients (n=33, combined studies), multiple dosing of atazanavir 300 mg once daily with 

ritonavir 100 mg once daily with food produced a geometric mean (CV%) for atazanavir, Cmax of 4466 (42%) 

ng/ml, with time to Cmax of approximately 2.5 hours. The geometric mean (CV%) for atazanavir Cmin and 

AUC was 654 (76%) ng/ml and 44185 (51%) ng•h/ml, respectively.  

 

In HIV-infected patients (n=13), multiple dosing of atazanavir 400 mg (without ritonavir) once daily with 

food produced a geometric mean (CV%) for atazanavir Cmax of 2298 (71) ng/ml, with time to Cmax of 

approximately 2.0 hours. The geometric mean (CV%) for atazanavir Cmin and AUC were 120 (109) ng/ml 

and 14874 (91) ng•h/ml, respectively. 

 

Food effect 

Co-administration of atazanavir and ritonavir with food optimises the bioavailability of atazanavir. Co-

administration of a single 300 mg dose of atazanavir and 100 mg dose of ritonavir with a light meal resulted 

in a 33% increase in the AUC and a 40% increase in both the Cmax and the 24 hour concentration of 

atazanavir relative to the fasting state. Co-administration with a high-fat meal did not affect the AUC of 

atazanavir relative to fasting conditions and the Cmax was within 11% of fasting values. The 24 hour 

concentration following a high fat meal was increased by approximately 33% due to delayed absorption; the 

median Tmax increased from 2.0 to 5.0 hours. Administration of atazanavir with ritonavir with either a light or 

a high-fat meal decreased the coefficient of variation of AUC and Cmax by approximately 25% compared to 

the fasting state. To enhance bioavailability and minimise variability, atazanavir is to be taken with food.  

 

Distribution 

 

Atazanavir was approximately 86% bound to human serum proteins over a concentration range of 100 to 

10,000 ng/ml. Atazanavir binds to both alpha-1-acid glycoprotein (AAG) and albumin to a similar extent 

(89% and 86%, respectively, at 1,000 ng/ml). In a multiple-dose study in HIV-infected patients dosed with 

400 mg of atazanavir once daily with a light meal for 12 weeks, atazanavir was detected in the cerebrospinal 

fluid and semen.  

 

Biotransformation 

 

Studies in humans and in vitro studies using human liver microsomes have demonstrated that atazanavir is 

principally metabolised by CYP3A4 isozyme to oxygenated metabolites. Metabolites are then excreted in the 

bile as either free or glucuronidated metabolites. Additional minor metabolic pathways consist of 

N-dealkylation and hydrolysis. Two minor metabolites of atazanavir in plasma have been characterised. 

Neither metabolite demonstrated in vitro antiviral activity. 

 

Elimination 

 

Following a single 400 mg dose of 14C-atazanavir, 79% and 13% of the total radioactivity was recovered in 

the faeces and urine, respectively. Unchanged drug accounted for approximately 20% and 7% of the 

administered dose in the faeces and urine, respectively. Mean urinary excretion of unchanged drug was 7% 

following 2 weeks of dosing at 800 mg once daily. In HIV-infected adult patients (n=33, combined studies) 

the mean half-life within a dosing interval for atazanavir was 12 hours at steady state following a dose of 

300 mg daily with ritonavir 100 mg once daily with a light meal. 

 

Special populations 

 

Renal impairment 



36 

In healthy subjects, the renal elimination of unchanged atazanavir was approximately 7% of the administered 

dose. There are no pharmacokinetic data available for atazanavir with ritonavir in patients with renal 

insufficiency. Atazanavir (without ritonavir) has been studied in adult patients with severe renal impairment 

(n=20), including those on haemodialysis, at multiple doses of 400 mg once daily. Although this study 

presented some limitations (i.e., unbound drug concentrations not studied), results suggested that the 

atazanavir pharmacokinetic parameters were decreased by 30% to 50% in patients undergoing haemodialysis 

compared to patients with normal renal function. The mechanism of this decrease is unknown. (See sections 

4.2 and 4.4.)  

 

Hepatic impairment 

Atazanavir is metabolised and eliminated primarily by the liver. Atazanavir (without ritonavir) has been 

studied in adult subjects with moderate-to-severe hepatic impairment (14 Child-Pugh Class B and 2 Child-

Pugh Class C subjects) after a single 400 mg dose. The mean AUC(0-∞) was 42% greater in subjects with 

impaired hepatic function than in healthy subjects. The mean half-life of atazanavir in hepatically impaired 

subjects was 12.1 hours compared to 6.4 hours in healthy subjects. The effects of hepatic impairment on the 

pharmacokinetics of atazanavir after a 300 mg dose with ritonavir have not been studied. Concentrations of 

atazanavir with or without ritonavir are expected to be increased in patients with moderately or severely 

impaired hepatic function (see sections 4.2, 4.3, and 4.4).  

 

Age/gender 

A study of the pharmacokinetics of atazanavir was performed in 59 healthy male and female subjects (29 

young, 30 elderly). There were no clinically important pharmacokinetic differences based on age or gender.  

 

Race 

A population pharmacokinetic analysis of samples from Phase II clinical trials indicated no effect of race on 

the pharmacokinetics of atazanavir.  

 

Pregnancy 

The pharmacokinetic data from HIV-infected pregnant women receiving atazanavir capsules with ritonavir 

are presented in Table 8.  

 

Table 8:  Steady-State Pharmacokinetics of Atazanavir with ritonavir in HIV-Infected Pregnant 

Women in the Fed State  

  atazanavir 300 mg with ritonavir 100 mg 

Pharmacokinetic Parameter 2nd Trimester  

(n=9)  

3rd Trimester  

(n=20)  

postpartuma  

(n=36)  

Cmax ng/mL  

Geometric mean (CV%)  

3729.09  

(39)  

3291.46  

(48)  

5649.10  

(31)  

AUC ng•h/mL  

Geometric mean (CV%)  

34399.1  

(37)  

34251.5  

(43)  

60532.7  

(33)  

Cmin ng/mLb  

Geometric mean (CV%)  

663.78  

(36)  

668.48  

(50)  

1420.64  

(47)  
a Atazanavir peak concentrations and AUCs were found to be approximately 26-40% higher during the 

postpartum period (4-12 weeks) than those observed historically in HIV infected, non-pregnant patients. 

Atazanavir plasma trough concentrations were approximately 2-fold higher during the postpartum period 

when compared to those observed historically in HIV infected non-pregnant patients.  
b Cmin is concentration 24 hours post-dose.  

 

Paediatric population  
There is a trend toward a higher clearance in younger children when normalised for body weight. As a result, 

greater peak to trough ratios are observed, however at recommended doses, geometric mean atazanavir 

exposures (Cmin, Cax and AUC) in paediatric patients are expected to be similar to those observed in adults. 

 



37 

5.3 Preclinical safety data 

 

In repeat-dose toxicity studies, conducted in mice, rats, and dogs, atazanavir-related findings were generally 

confined to the liver and included generally minimal to mild increases in serum bilirubin and liver enzymes, 

hepatocellular vacuolation and hypertrophy, and, in female mice only, hepatic single-cell necrosis. Systemic 

exposures of atazanavir in mice (males), rats, and dogs at doses associated with hepatic changes were at least 

equal to that observed in humans given 400 mg once daily. In female mice, atazanavir exposure at a dose that 

produced single-cell necrosis was 12 times the exposure in humans given 400 mg once daily. Serum 

cholesterol and glucose were minimally to mildly increased in rats but not in mice or dogs.  

 

During in vitro studies, cloned human cardiac potassium channel (hERG), was inhibited by 15% at a 

concentration (30 μM) of atazanavir corresponding to 30 fold the free drug concentration at Cmax in humans. 

Similar concentrations of atazanavir increased by 13% the action potential duration (APD90) in rabbit 

Purkinje fibres study. Electrocardiographic changes (sinus bradycardia, prolongation of PR interval, 

prolongation of QT interval, and prolongation of QRS complex) were observed only in an initial 2 week oral 

toxicity study performed in dogs. Subsequent 9 month oral toxicity studies in dogs showed no drug-related 

electrocardiographic changes. The clinical relevance of these non-clinical data is unknown. Potential cardiac 

effects of this product in humans cannot be ruled out (see sections 4.4 and 4.8). The potential for PR 

prolongation should be considered in cases of overdose (see section 4.9).  

 

In a fertility and early embryonic development study in rats, atazanavir altered oestrus cycling with no 

effects on mating or fertility. No teratogenic effects were observed in rats or rabbits at maternally toxic 

doses. In pregnant rabbits, gross lesions of the stomach and intestines were observed in dead or moribund 

does at maternal doses 2 and 4 times the highest dose administered in the definitive embryo-development 

study. In the pre- and postnatal development assessment in rats, atazanavir produced a transient reduction in 

body weight in the offspring at a maternally toxic dose. Systemic exposure to atazanavir at doses that 

resulted in maternal toxicity was at least equal to or slightly greater than that observed in humans given 

400 mg once daily.  

 

Atazanavir was negative in an Ames reverse-mutation assay but did induce chromosomal aberrations in vitro 

in both the absence and presence of metabolic activation. In in vivo studies in rats, atazanavir did not induce 

micronuclei in bone marrow, DNA damage in duodenum (comet assay), or unscheduled DNA repair in liver 

at plasma and tissue concentrations exceeding those that were clastogenic in vitro.  

 

In long-term carcinogenicity studies of atazanavir in mice and rats, an increased incidence of benign hepatic 

adenomas was seen in female mice only. The increased incidence of benign hepatic adenomas in female 

mice was likely secondary to cytotoxic liver changes manifested by single-cell necrosis and is considered to 

have no relevance for humans at intended therapeutic exposures. There were no tumorigenic findings in male 

mice or in rats.  

 

Atazanavir increased opacity of bovine corneas in an in vitro ocular irritation study, indicating it may be an 

ocular irritant upon direct contact with the eye.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Capsule contents 

 

Lactose monohydrate  

Crospovidone 

Magnesium stearate  

 



38 

Capsule shell cap 150 mg 

 

Iron oxide red (E172) 

Titanium dioxide (E171) 

Patent blue V (E131) 

Gelatin 

 

Capsule shell body 150 mg 

 

Titanium dioxide (E171) 

Patent blue V (E131) 

Gelatin 

 

Capsule shell cap 200 mg 

 

Titanium dioxide (E171) 

Indigo Carmine (E132) 

Gelatin 

 

Capsule shell body 200 mg 

 

Iron oxide yellow (E172) 

Titanium dioxide (E171) 

Patent blue V (E131) 

Gelatin 

 

Capsule shell cap 300 mg 

 

Iron oxide yellow (E172) 

Iron oxide red (E172) 

Titanium dioxide (E171) 

Gelatin 

 

Capsule shell body 300 mg 

 

Iron oxide red (E172) 

Titanium dioxide (E171) 

Patent blue V (E131) 

Gelatin 

 

Printing ink 

 

Shellac 

Propylene glycol 

Ammonia solution, concentrated 

Iron oxide black (E172) 

Potassium hydroxide 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 

 

3 years 



39 

For bottles: Use within 90 days of first opening 

 

6.4 Special precautions for storage 

 

Store below 25°C. Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container  
 

150 mg 

 

OPA/Aluminium/PVC – Aluminium blisters containing 60, 60 x 1 (unit dose) capsules. 

PVC/PVDC/Aluminium blisters containing 60, 60 x 1 (unit dose) capsules. 

HDPE bottle with polypropylene screw cap containing 60 capsules. 

 

200 mg 

 

OPA/Aluminium/PVC – Aluminium blisters containing 60, 60 x 1 (unit dose) capsules. 

PVC/PVDC/Aluminium blisters containing 30, 60, 60 x 1 (unit dose) capsules. 

HDPE bottle with polypropylene screw cap containing 60 capsules. 

 

300 mg 

 

OPA/Aluminium/PVC – Aluminium blisters containing 30, 30 x 1 (unit dose) capsules. 

PVC/PVDC/Aluminium blisters containing 30, 30 x 1 (unit dose) capsules. 

HDPE bottle with polypropylene screw cap containing 30, 90 capsules. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal  

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements.  

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/001 

EU/1/16/1091/002 

EU/1/16/1091/003 

EU/1/16/1091/004 

EU/1/16/1091/005 

EU/1/16/1091/006 

EU/1/16/1091/007 

EU/1/16/1091/008 



40 

EU/1/16/1091/009 

EU/1/16/1091/010 

EU/1/16/1091/011 

EU/1/16/1091/012 

EU/1/16/1091/013 

EU/1/16/1091/014 

EU/1/16/1091/015 

EU/1/16/1091/016 

EU/1/16/1091/017 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation:  22 August 2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

  



41 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

  



42 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13 

Ireland 

 

Mylan B.V. 

Dieselweg 25, 3752 LB Bunschoten 

The Netherlands 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352,  

Germany  

 

The printed package leaflet of the medicinal product must state the name and address of the manufacturer 

responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 

 

Periodic Safety Update Reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are set out in 

the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE 

OF THE MEDICINAL PRODUCT   

 

Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed 

RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the 

RMP. 

 

An updated RMP should be submitted: 

At the request of the European Medicines Agency; 

Whenever the risk management system is modified, especially as the result of new information being 

received that may lead to a significant change to the benefit/risk profile or as the result of an important 

(pharmacovigilance or risk minimisation) milestone being reached. 

 



43 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



44 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



45 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BLISTER CARTON FOR 150 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 150 mg hard capsules  

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 150 mg atazanavir (as sulphate).  

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules. 

60 x 1 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 



46 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/001 

EU/1/16/1091/002 

EU/1/16/1091/011 

EU/1/16/1091/012 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 150 mg hard capsules 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN:  



47 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR 150 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 150 mg hard capsules 

atazanavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



48 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BOTTLE CARTON FOR 150 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 150 mg hard capsules 

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 150 mg of atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

Date opened: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

 



49 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/003 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 150 mg hard capsules 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  

 

 



50 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL FOR 150 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 150 mg hard capsules 

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 150 mg atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules. 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

Oral use. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

 



51 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/003 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

 

 

  



52 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BLISTER CARTON FOR 200 MG HARD CAPSULES  

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 200 mg hard capsules  

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 200 mg of atazanavir (as sulphate)  

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules 

60 hard capsules. 

60 x 1 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 



53 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/004 

EU/1/16/1091/005 

EU/1/16/1091/013 

EU/1/16/1091/014 

EU/1/16/1091/015 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 200 mg hard capsules 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC:  

SN:  

NN:   



54 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR 200 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 200 mg hard capsules  

atazanavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



55 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BOTTLE CARTON FOR 200 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 200 mg hard capsules 

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 200 mg of atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

Date opened: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

 



56 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 200 mg hard capsules  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  

 

 



57 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE 

 

BOTTLE LABEL FOR 200 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 200 mg hard capsules 

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 200 mg atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

60 hard capsules. 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

Oral use. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

 



58 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

  



59 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BLISTER CARTON FOR 300 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 300 mg hard capsules 

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 300 mg of atazanavir (as sulphate).  

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules.  

30 x 1 hard capsules.  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

N/A 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the originalpackage in order to protect from moisture. 



60 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/007 

EU/1/16/1091/008 

EU/1/16/1091/016 

EU/1/16/1091/017 

 

 

13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 300 mg hard capsules 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC:  

SN:  

NN:   



61 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS FOR 300 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 300 mg hard capsules 

atazanavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



62 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

BOTTLE CARTON FOR 300 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 300 mg hard capsules  

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each hard capsule contains 300 mg of atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules. 

90 hard capsules. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Capsules should be swallowed whole. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

Date opened: 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 



63 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/009 

EU/1/16/1091/010 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Atazanavir Mylan 300 mg hard capsules 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC:  

SN:  

NN:  

 



64 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL FOR 300 MG HARD CAPSULES 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atazanavir Mylan 300 mg hard capsules  

atazanavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 300 mg atazanavir (as sulphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

30 hard capsules. 

90 hard capsules. 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

Oral use. Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened: Use within 90 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

 



65 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

Saint-Priest 

69800 

France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/16/1091/009 

EU/1/16/1091/010 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

  



66 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



67 

Package leaflet: Information for the user 

 

Atazanavir Mylan 150 mg hard capsules 

Atazanavir Mylan 200 mg hard capsules 

Atazanavir Mylan 300 mg hard capsules 

 

atazanavir 

 

Read all of this leaflet carefully before you start taking this medicine because it contains important 

information for you. 

- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if 

their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Atazanavir Mylan is and what it is used for  

2. What you need to know before you take Atazanavir Mylan  

3. How to take Atazanavir Mylan  

4. Possible side effects  

5. How to store Atazanavir Mylan 

6. Contents of the pack and other information 

 

 

1. What Atazanavir Mylan is and what it is used for 

 

Atazanavir Mylan is an antiviral (or antiretroviral) medicine. It is one of a group called protease 

inhibitors. These medicines control Human Immunodeficiency Virus (HIV) infection by stopping a protein 

that the HIV needs for its multiplication. They work by reducing the amount of HIV in your body and this in 

turn, strengthens your immune system. In this way Atazanavir Mylan reduces the risk of developing illnesses 

linked to HIV infection. 

 

Atazanavir Mylan capsules may be used by adults and children 6 years of age and older. Your doctor has 

prescribed Atazanavir Mylan for you because you are infected by the HIV that causes Acquired 

Immunodeficiency Syndrome (AIDS). It is normally used in combination with other anti-HIV medicines. 

Your doctor will discuss with you which combination of these medicines with Atazanavir Mylan is best for 

you. 

 

 

2. What you need to know before you take Atazanavir Mylan  

 

Do not take Atazanavir Mylan 

• if you are allergic to atazanavir or any of the other ingredients of this medicine (listed in section 6) 

• if you have moderate to severe liver problems. Your doctor will evaluate how severe your liver 
disease is before deciding whether you can take Atazanavir Mylan 

• if you are taking any of these medicines: see also Other medicines and Atazanavir Mylan 
- rifampicin, an antibiotic used to treat tuberculosis 
- astemizole or terfenadine (commonly used to treat allergy symptoms, these medicines may be 

available without prescription); cisapride (used to treat gastric reflux, sometimes called 

heartburn); pimozide (used to treat schizophrenia); quinidine or bepridil (used to correct heart 

rhythm); ergotamine, dihydroergotamine, ergonovine, methylergonovine (used to treat 

headaches); and alfuzosin (used to treat enlarged prostatic gland). 



68 

• quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder). 

• lurasidone (used to treat schizophrenia). 

• medicines containing St. John’s wort (Hypericum perforatum, a herbal preparation). 

• triazolam and oral (taken by mouth) midazolam (used to help you sleep and/or to relieve anxiety). 

• simvastatin and lovastatin (used to lower blood cholesterol). 
• grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination, and 

glecaprevir/pibrentasvir fixed dose combination (used to treat chronic hepatitis C infection). 

 

Do not take sildenafil with Atazanavir Mylan when sildenafil is used for the treatment of pulmonary arterial 

hypertension. Sildenafil is also used for the treatment of erectile dysfunction. Tell your doctor if you are 

using sildenafil for the treatment of erectile dysfunction. 

 

Tell your doctor at once if any of these apply to you. 

 
Warnings and precautions 
 

Atazanavir Mylan is not a cure for HIV infection. You may continue to develop infections or other 

illnesses linked to HIV infection. You can still pass on HIV when taking this medicine, although the risk is 

lowered by effective antiretroviral therapy. Discuss with your doctor the precautions needed to avoid 

infecting other people. 
 
Some people will need special care before or while taking Atazanavir Mylan. Talk to your doctor or 
pharmacist before taking Atazanavir Mylan and make sure your doctor knows: 

• if you have hepatitis B or C 

• if you develop signs or symptoms of gall stones (pain at the right side of your stomach) 

• if you have type A or B haemophilia 

• if you require haemodialysis 
 
Atazanavir may affect how well your kidneys work. 

 

Kidney stones have been reported in patients taking atazanavir. If you develop signs or symptoms of kidney 

stones (pain in your side, blood in your urine, pain when you urinate), please inform your doctor 

immediately. 

 
In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and 

symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is 

believed that these symptoms are due to an improvement in the body’s immune response, enabling the body 

to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of 

infection, please inform your doctor immediately. In addition to the opportunistic infections, autoimmune 

disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after 

you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many 

months after the start of treatment. If you notice any symptoms of infection or other symptoms such as 

muscle weakness, weakness beginning in hands and feet and moving up towards the trunk of the body, 

palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment. 

 
Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis 

(death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral 

therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, 

among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are 

joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you 

notice any of these symptoms please inform your doctor. 

 

Hyperbilirubinaemia (an increase in the level of bilirubin in the blood) has occurred in patients 

receiving atazanavir. The signs may be a mild yellowing of the skin or eyes. If you notice any of these 

symptoms please inform your doctor. 

 



69 

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking atazanavir. If 

you develop a rash inform your doctor immediately. 
 
If you notice a change in the way your heart beats (heart rhythm changes), please inform your doctor. 

 

Children receiving Atazanavir Mylan may require their heart to be monitored. Your child’s doctor will 

decide this. 

 

Children 

Do not give this medicine to children younger than 3 months of age and weighing less than 5 kg. The use 

of atazanavir in children less than 3 months of age and weighing less than 5 kg has not been studied due to 

the risk of serious complications. 

 

Other medicines and Atazanavir Mylan 

You must not take Atazanavir Mylan with certain medicines. These are listed under Do not take Atazanavir 

Mylan, at the start of Section 2.  

 

There are other medicines that may not mix with Atazanavir Mylan. Tell your doctor or pharmacist if you are 

taking, have recently taken or might take any other medicines. It is especially important to mention these: 

• other medicines to treat HIV infection (e.g. indinavir, nevirapine and efavirenz) 

• boceprevir and sofosbuvir/velpatasvir/voxilaprevir (used to treat hepatitis C) 

• sildenafil, vardenafil, or tadalafil (used by men to treat impotence (erectile dysfunction)) 

• if you are taking an oral contraceptive ("the Pill") with Atazanavir Mylan to prevent pregnancy, be 
sure to take it exactly as instructed by your doctor and not miss any doses. 

• any medicines used to treat diseases related to the acid in the stomach (e.g. antacids to be taken 
1 hour before taking Atazanavir Mylan or 2 hours after taking Atazanavir Mylan, H2-blockers like 

famotidine and proton pump inhibitors like omeprazole) 

• medicines to lower blood pressure, to slow heart rate, or to correct heart rhythm (amiodarone, 
diltiazem, systemic lidocaine, verapamil) 

• atorvastatin, pravastatin, and fluvastatin (used to lower blood cholesterol) 

• salmeterol (used to treat asthma) 

• ciclosporin, tacrolimus, and sirolimus (medicines to decrease the effects of body’s immune system) 

• certain antibiotics (rifabutin, clarithromycin) 

• ketoconazole, itraconazole, and voriconazole (antifungals) 

• warfarin (anticoagulant, used to reduce the blood clots) 

• carbamazepine, phenytoin, phenobarbital, lamotrigine (antiepileptics) 

• irinotecan (used to treat cancer) 

• sedative agents (e.g. midazolam administered by injection) 

• buprenorphine (used to treat opioid addiction and pain). 
 

Some medicines may interact with ritonavir, a medicine that is taken with Atazanavir Mylan. It is important 

to tell your doctor if you are taking fluticasone or budesonide (given by nose or inhaled to treat allergic 

symptoms or asthma). 

 

Atazanavir Mylan with food and drink 

It is important that you take Atazanavir Mylan with food (a meal or a substantial snack) as this helps the 

body absorb the medicine. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think that you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. Atazanavir, the active substance of 

Atazanavir Mylan, is excreted in human milk. Patients should not breast-feed while taking Atazanavir Mylan. 

It is recommended that women infected with HIV do not breast-feed because the virus might be transmitted 

through the breast milk. 

 

Driving and using machines 



70 

If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately. 

 

Atazanavir Mylan contains lactose  

If you have been told by your doctor that you have an intolerance to some sugars (e.g. lactose), contact your 

doctor before taking this medicinal product. 

 

 

3. How to take Atazanavir Mylan 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you 

are not sure. This way, you can be sure your medicine is fully effective and you reduce the risk of the virus 

developing resistance to the treatment.   

 

The recommended dose of Atazanavir Mylan capsules for adults is 300 mg once daily with 100 mg 

ritonavir once daily, taken with food, in combination with other anti-HIV medicines. Your doctor may 

adjust the dose of Atazanavir Mylan according to your anti-HIV therapy. 

 

For children (6 to less than 18 years of age), your child’s doctor will decide the right dose based on 

your child’s weight. The dose of Atazanavir Mylan capsules for children is calculated by body weight and is 

taken once daily with food and 100 mg ritonavir as shown below: 
 

Body Weight (kg) Atazanavir Mylan dose once 
daily (mg) 

Ritonavir Dose* once daily 
 (mg) 

15 to less than 35 200 100 
At least 35 300 100 

* Ritonavir capsules, tablets or oral solution may be used. 

 

Other forms of this medicine may be available for use in children at least 3 months old and weighing at least 

5 kg. Switching to capsules from other formulations is encouraged as soon as patients are able to consistently 

swallow capsules. 

 

A change in dose may occur when switching between other formulations and capsules. Your doctor will 

decide the right dose based on your child’s weight. 

 

There are no dosing recommendations for Atazanavir Mylan in paediatric patients less than 3 months of age. 
 
Take Atazanavir Mylan capsules with food (a meal or a substantial snack). Swallow the capsules whole. 
Do not open the capsules. 

 

If you take more Atazanavir Mylan than you should 

Yellowing of the skin and/or eyes (jaundice) and irregular heart beat (QTc prolongation) may occur if you or your 

child take too much Atazanavir Mylan. 

If you accidentally take more Atazanavir Mylan capsules than your doctor recommended, contact your HIV 

doctor at once or contact the nearest hospital for advice. 

 

If you forget to take Atazanavir Mylan 

If you miss a dose, take the missed dose as soon as possible with food and then take your next scheduled dose 

at its regular time. If it is almost time for your next dose, do not take the missed dose. Wait and take the next 

dose at its regular time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Atazanavir Mylan 

Do not stop taking Atazanavir Mylan before talking to your doctor. If you have any further questions on the 

use of this medicine, ask your doctor or pharmacist. 

 

 



71 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. When treating 

HIV infection, it is not always easy to identify what side effects are caused by atazanavir, by the other 

medicines you are taking, or by the HIV infection itself. Tell your doctor if you notice anything unusual 

about your health. 

 

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is 

partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines 

themselves. Your doctor will test for these changes. 

 
Tell your doctor immediately if you develop any of the following serious side effects: 
 

• Skin rash, itching that may occasionally be severe has been reported. The rash usually disappears 

within 2 weeks without any change to your treatment. Severe rash may be developed in association 

with other symptoms which could be serious. Stop taking Atazanavir Mylan and talk to your doctor 

immediately if you develop a severe rash or a rash with flu-like illness symptoms, blisters, fever, 

mouth sores, muscle or joint pain, swelling in the face, inflammation of the eye which causes redness 

(conjunctivitis), painful, warm, or red lumps (nodules).  

• Yellowing of your skin or the white part of your eyes caused by high levels of bilirubin in your blood 

has been commonly reported. This side effect is usually not dangerous in adults and infants older 

than 3 months of age; but it might be a symptom of a serious problem. If your skin or the white part 

of your eyes turns yellow, talk to your doctor immediately. 

• Changes in the way your heart beats (heart rhythm change) may occasionally happen. Talk to your 

doctor immediately if you get dizzy, lightheaded or if you suddenly faint. These could be symptoms 

of a serious heart problem.  

• Liver problems may uncommonly happen. Your doctor should do blood tests prior you starting to 

take this medicine and during treatment. If you have liver problems, including hepatitis B or C 

infection, you may experience a worsening of your liver problems. Talk to your doctor immediately 

if you get dark (tea-colored) urine, itching, yellowing of your skin or the white part of your eyes, 

pain around the stomach, pale colored stools or nausea. 

• Gallbladder problems uncommonly happen in people taking atazanavir. Symptoms of gallbladder 

problems may include pain in the right or middle upper stomach area, nausea, vomiting, fever or 

yellowing your skin or the white part of your eyes. 

• Atazanavir may affect how well your kidneys work. 

• Kidney stones uncommonly happen in people taking atazanavir. Talk to your doctor immediately if 

you get symptoms of kidney stones which may include, pain in your low back or low stomach-area, 

blood in your urine or pain when you urinate. 
 
Other side effects reported for patients treated with atazanavir are the following: 
 
Common (may affect up to 1 in 10 people): 

• headache 
• vomiting, diarrhoea, abdominal pain (stomach pain of discomfort), nausea, dyspepsia (indigestion) 

• fatigue (extreme tiredness) 
 
Uncommon (may affect up to 1 in 100 people): 

• peripheral neuropathy (numbness, weakness, tingling or pain in the arms and legs) 

• hypersensitivity (allergic reaction) 
• asthenia (unusual tiredness or weakness) 

• weight decreased, weight gain, anorexia (loss of appetite), appetite increased 
• depression, anxiety, sleep disorder 

• disorientation, amnesia (loss of memory), dizziness, somnolence (sleepiness), abnormal dream 
• syncope (fainting), hypertension (high blood pressure) 
• dyspnoea (shortness of breath) 



72 

• pancreatitis (inflammation of the pancreas), gastritis (inflammation of the stomach), stomatitis 
aphthous (mouth ulcers and cold sores), dysgeusia (impairment of the sense of taste), flatulence 

(wind), dry mouth, abdominal distension 

• angioedema (severe swelling of the skin and other tissues most often the lips or the eyes) 

• alopecia (unusual hair loss or thinning), pruritus (itching) 
• muscle atrophy (muscle shrinkage), arthralgia (joint pain), myalgia (aching muscles) 
• interstitial nephritis (kidney inflammation), haematuria (blood in the urine), proteinuria (excess 

protein in the urine), pollakiuria (increased frequency of urination) 

• gynaecomastia (breast enlargement in men) 
• chest pain, malaise (generally feeling unwell), fever 

• insomnia (difficulty sleeping) 
 

Rare (may affect up to 1 in 1,000 people): 

• gait disturbance (abnormal manner of walking) 
• oedema (swelling) 
• hepatosplenomegaly (enlargement of the liver and spleen) 
• myopathy (aching muscles, muscle tenderness of weakness, not caused by exercise) 
• kidney pain 

 
Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Atazanavir Mylan 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the label, carton or blister. The expiry date 

refers to the last day of that month. 

Store below 25ºC. Store in the original package in order to protect from moisture. 

 

For bottles: Once opened, use within 90 days. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw 

away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Atazanavir Mylan contains  

 

Atazanavir Mylan 150 mg hard capsules 

- The active substance is atazanavir. Each capsule contains 150 mg or atazanavir (as sulphate). 
- The other ingredients are lactose monohydrate (see section 2, ‘Atazanavir Mylan contains lactose’), 

crospovidone, magnesium stearate. The capsule shell and printing ink contain iron oxide red (E172), 

titanium dioxide (E171), patent blue V (E131), gelatin, shellac, propylene glycol, concentrated 

ammonia solution, iron oxide black (E172), potassium hydroxide. 

 

Atazanavir Mylan 200 mg hard capsules 

- The active substance is atazanavir. Each capsule contains 200 mg or atazanavir (as sulphate). 
- The other ingredients are lactose monohydrate (see section 2, ‘Atazanavir Mylan contains lactose’), 

crospovidone, magnesium stearate. The capsule shell and printing ink contain titanium dioxide (E171), 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


73 

indigo carmine (E132), iron oxide yellow (E172), patent blue V (E131), gelatin, shellac, propylene 

glycol, concentrated ammonia solution, iron oxide black (E172), potassium hydroxide. 

 

Atazanavir Mylan 300 mg hard capsules 

- The active substance is atazanavir. Each capsule contains 300 mg or atazanavir (as sulphate). 
- The other ingredients are lactose monohydrate, crospovidone, magnesium stearate. The capsule shell 

and printing ink contain iron oxide yellow (E172), iron oxide red (E172), titanium dioxide (E171),  

patent blue V (E131), gelatin, shellac, propylene glycol, concentrated ammonia solution, iron oxide 

black (E172), potassium hydroxide. 

 

 

What Atazanavir Mylan looks like and contents of the pack 

 

Atazanavir Mylan 150 mg hard capsules are greenish-blue and blue opaque capsules with ‘MYLAN’ over 

‘AR150’ printed in black ink on cap and body.   

 

Atazanavir Mylan 200 mg hard capsules are blue and greenish-blue opaque capsules with ‘MYLAN’ over 

‘AR200’ printed in black ink on cap and body. 

 

Atazanavir Mylan 300 mg hard capsules are red and greenish-blue opaque capsules with ‘MYLAN’ over 

‘AR300’ printed in black ink on cap and body. 

 

Atazanavir Mylan 150 mg hard capsules 

This medicine comes in blister packs containing 60 or 60 x 1 (unit dose) capsules or in  bottles containing 60 

hard capsules. 

 

Atazanavir Mylan 200 mg hard capsules 

This medicine comes in blister packs containing 30, 60 or 60 x 1 (unit dose) capsules or in  bottles containing 

60 hard capsules. 

 

Atazanavir 300 mg hard capsules 

This medicine comes in blister packs containing 30 or 30 x 1 (unit dose) capsules or in bottles containing 30 

or 90 hard capsules. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

 

Mylan S.A.S., 117 Allee des Parcs, Saint-Priest, 69800, France 

 

Manufacturer 

McDermott Laboratories trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, 

Dublin 13, Ireland 

 

Mylan Hungary Kft, Mylan utca 1, Komárom, H-2900 Hungary 

 

Mylan B.V., Dieselweg 25, 3752 LB Bunschoten, The Netherlands 

 

Mylan Germany GmbH, Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe, Hessen, 61352, Germany  

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 



74 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: +32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: +32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100  

Danmark 

Mylan Denmark ApS 

Tlf: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH  

Tel: +49 800 0700 800 

 

Nederland 

Mylan B.V. 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: +47 66 75 33 00 

 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ: +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L. 

Tel: +34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: +48 22 564 64 00 

 

France 

Mylan S.A.S. 

Tél: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: +351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599  

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: +386 1 236 31 80 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s r. o  

Tel: +421 2 32 199 100  



75 

Italia 

Mylan Italia S.r.l. 

Tel: +39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 222 077 00 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA 

Tel: +371 676 055 80 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in  

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu.  

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET