Reyataz

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 100 mg hard capsules 
REYATAZ 150 mg hard capsules 
REYATAZ 200 mg hard capsules 
REYATAZ 300 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
REYATAZ 100 mg hard capsules 
Each capsule contains 100 mg of atazanavir (as sulphate). 
 
Excipient with known effect: 54.79 mg of lactose per capsule. 
 
REYATAZ 150 mg hard capsules 
Each capsule contains 150 mg of atazanavir (as sulphate). 
 
Excipient with known effect: 82.18 mg of lactose per capsule. 
 
REYATAZ 200 mg hard capsules 
Each capsule contains 200 mg of atazanavir (as sulphate). 
 
Excipient with known effect: 109.57 mg of lactose per capsule. 
 
REYATAZ 300 mg hard capsules 
Each capsule contains 300 mg of atazanavir (as sulphate). 
 
Excipient with known effect: 164.36 mg of lactose per capsule. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule 
 
REYATAZ 100 mg hard capsules 
Opaque blue and white capsule printed with white and blue inks, with "BMS 100 mg" on one half and 
with "3623" on the other half. 
 
REYATAZ 150 mg hard capsules 
Opaque blue and powder blue capsule printed with white and blue inks, with "BMS 150 mg" on one 
half and with "3624" on the other half. 
 
REYATAZ 200 mg hard capsules 
Opaque blue capsule printed with white ink, with "BMS 200 mg" on one half and with "3631" on the 
other half. 
 
REYATAZ 300 mg hard capsules 
Opaque red and blue capsule printed with white ink, with "BMS 300 mg" on one half and with "3622" 
on the other half. 
 
 



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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
REYATAZ capsules, co-administered with low dose ritonavir, are 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 REYATAZ 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 REYATAZ capsules 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. REYATAZ capsules must be taken with ritonavir 
and have to be taken with food. 
 
Table 1: Dose for paediatric patients (6 years to less than 18 years of age and weighing at 

least 15 kg) for REYATAZ capsules with ritonavir 
Body Weight (kg) REYATAZ 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): REYATAZ oral powder is 
available for paediatric patients at least 3 months of age and weighing at least 5 kg (see Summary of 
Product Characteristics for REYATAZ oral powder). Switching to REYATAZ capsules from 
REYATAZ oral powder 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 Summary of Product Characteristics for REYATAZ oral powder). 
 
Special populations 
Renal impairment 
No dosage adjustment is needed. REYATAZ with ritonavir is not recommended in patients 
undergoing haemodialysis (see sections 4.4 and 5.2). 
 
Hepatic impairment 
REYATAZ with ritonavir has not been studied in patients with hepatic impairment. REYATAZ with 
ritonavir should be used with caution in patients with mild hepatic impairment. REYATAZ 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 REYATAZ could be maintained in patients with mild hepatic impairment 



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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 REYATAZ must not be used in patients with severe 
hepatic impairment. 
 
Pregnancy and Postpartum 
During the second and third trimesters of pregnancy: 
REYATAZ 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 REYATAZ 

400 mg with ritonavir 100 mg with TDM may be considered (see sections 4.6 and 5.2). 
 It is not recommended to use REYATAZ 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) 
REYATAZ 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. 
 
REYATAZ is contraindicated in patients with severe hepatic insufficiency 
(see sections 4.2, 4.4 and 5.2). REYATAZ 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). 



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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 REYATAZ 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 REYATAZ 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, 
REYATAZ is not recommended in patients undergoing haemodialysis (see sections 4.2 and 5.2). 
 
QT prolongation: Dose related asymptomatic prolongations in PR interval with REYATAZ 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), REYATAZ should be used with caution and only if 
the benefits exceed the risk (see section 5.1). Particular caution should be used when prescribing 
REYATAZ 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. 
 



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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, REYATAZ (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 REYATAZ (see section 4.8). Hepatic 
transaminase elevations that occur with elevated bilirubin in patients receiving REYATAZ should be 
evaluated for alternative aetiologies. Alternative antiretroviral therapy to REYATAZ 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 REYATAZ 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 REYATAZ boosted with ritonavir, ensuring optimal 
pharmacokinetic parameters and level of virologic suppression.  
The withdrawal of ritonavir from the boosted regimen of REYATAZ 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. 

 
REYATAZ 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 (see section 4.5 In case of withdrawal of ritonavir from the recommended 
atazanavir boosted regimen) or in case of perceived challenging compliance. 
 
REYATAZ 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 REYATAZ (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 REYATAZ (see section 4.8). Some patients 
required hospitalization for additional management and some had complications. In some cases, 



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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 occurs 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 REYATAZ.  
 
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 
REYATAZ. Patients should be advised of the signs and symptoms and monitored closely for skin 
reactions. REYATAZ 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 
REYATAZ, REYATAZ may not be restarted. 
 
Interactions with other medicinal products 
The combination of REYATAZ with atorvastatin is not recommended (see section 4.5). 
 
Co-administration of REYATAZ with nevirapine or efavirenz is not recommended (see section 4.5). 
If the co-administration of REYATAZ with an NNRTI is required, an increase in the dose of both 
REYATAZ 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 REYATAZ 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 REYATAZ. Co-administration of REYATAZ 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 REYATAZ 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). 



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Concomitant use of REYATAZ/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 REYATAZ may result in increased cardiovascular adverse events 
associated with salmeterol. Co-administration of salmeterol and REYATAZ 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 REYATAZ with proton pump inhibitors is not recommended (see section 4.5). If 
the combination of REYATAZ with a proton pump inhibitor is judged unavoidable, close clinical 
monitoring is recommended in combination with an increase in the dose of REYATAZ 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 REYATAZ 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 
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), REYATAZ 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, the Lapp 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 REYATAZ 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 
REYATAZ and ritonavir. 
 
Atazanavir is metabolised in the liver through CYP3A4. It inhibits CYP3A4. Therefore, REYATAZ 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 REYATAZ 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 REYATAZ with 
glecaprevir/pibrentasvir fixed dose combination is contraindicated because of the potential increase in 



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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 REYATAZ and other medicinal products 
 

Medicinal products by 
therapeutic area 

Interaction Recommendations concerning 
co-administration 

ANTI-HCV AGENTS 

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 
REYATAZ 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. 



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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%) 
 
*Lack of pharmacokinetics interaction 
bounds 70-143%  
 

Effect on atazanavir and ritonavir 
exposure has not been studied. 
Expected: 
↔ Atazanavir  
↔ Ritonavir  
 
The mechanism of interaction between 
REYATAZ/ritonavir and 
sofosbuvir/velpatasvir/voxilaprevir is 
inhibition of OATP1B, Pgp, and 
CYP3A. 

Co-administration of 
REYATAZ with voxilaprevir-
containing products is expected 
to increase the concentration of 
voxilaprevir. Co-administration 
of REYATAZ with 
voxilaprevir-containing 
regimens is not recommended. 

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 
REYATAZ with 
glecaprevir/pibrentasvir 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 REYATAZ/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. 



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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 
REYATAZ 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 
REYATAZ is not expected to 
significantly alter the exposure 
of the co-administered medicinal 
products. 

Abacavir The co-administration of abacavir and 
REYATAZ 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 
REYATAZ taken with food. 
The co-administration of 
stavudine with REYATAZ is 
not expected to significantly 
alter the exposure of stavudine. 



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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. 
 
Studies conducted in HIV-
infected patients 

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 300 mg 
(n=39) was compared to 
atazanavir/ritonavir 300/100 mg 
(n=33). 
 
The efficacy of REYATAZ/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. 

When co-administered with 
tenofovir disoproxil fumarate, it 
is recommended that 
REYATAZ 300 mg be given 
with ritonavir 100 mg and 
tenofovir disoproxil fumarate 
300 mg (all 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 REYATAZ is not 
recommended (see section 4.4) 
 



 13 

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 REYATAZ 
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%) * 
Atazanavir Cmax ↔2% (↓15% ↑24%) * 
Atazanavir Cmin ↓59% (↓73% ↓40%) * 
 
* When compared to REYATAZ 
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. 

Co-administration of nevirapine 
and REYATAZ is not 
recommended (see section 4.4) 

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.  



 14 

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%) 
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. 
 

No recommendation regarding 
dose reduction can be made; 
therefore, caution should be 
exercised if REYATAZ is co-
administered with 
clarithromycin. 

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 
REYATAZ/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, REYATAZ/ritonavir is 
expected to increase ketoconazole or 
itraconazole concentrations. 



 15 

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 REYATAZ 
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 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. 

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%) 
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.  
 

Fluconazole 200 mg once daily 
(atazanavir 300 mg and 
ritonavir 100 mg once daily) 

Atazanavir and fluconazole 
concentrations were not significantly 
modified when REYATAZ/ritonavir 
was co-administered with fluconazole. 

No dosage adjustments are 
needed for fluconazole and 
REYATAZ. 



 16 

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 REYATAZ, 
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 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 REYATAZ. 

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 
REYATAZ or other protease inhibitors 
with ritonavir, a high frequency of 
liver reactions was seen. 

The combination of rifampicin 
and REYATAZ is 
contraindicated (see section 4.3). 

ANTIPSYCHOTICS 

Quetiapine Due to CYP3A4 inhibition by 
REYATAZ, concentrations of 
quetiapine are expected to increase. 

Co-administration of quetiapine 
with REYATAZ is 
contraindicated as REYATAZ 
may increase quetiapine-related 
toxicity. Increased plasma 
concentrations of quetiapine 
may lead to coma 
(see section 4.3). 

Lurasidone REYATAZ is expected to increase 
plasma levels of lurasidone due to 
CYP3A4 inhibition. 

Co-administration of lurasidone 
with REYATAZ is contra-
ndicated as this may increase 
lurasidone-related toxicity 
(see section 4.3). 



 17 

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 REYATAZ 
300 mg/ritonavir 100 mg and 
H2-receptor antagonists are co-
administered, a dose equivalent 
to famotidine 20 mg 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 
REYATAZ/ritonavir dose from 
300/100 mg to 400/100 mg can 
be considered. 

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%) 
Atazanavir Cmax ↓23% (↓33% ↓12%) 
Atazanavir Cmin ↓20% (↓31% ↓8%) 

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 REYATAZ/ritonavir with 
both tenofovir disoproxil 
fumarate and an H2-receptor 
antagonist are co-administered, 
a dose increase of REYATAZ 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. 



 18 

Proton pump inhibitors 

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 
REYATAZ 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 REYATAZ 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 REYATAZ/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 REYATAZ.  

REYATAZ 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 
REYATAZ and/or ritonavir. 

Co-administration of alfuzosin 
with REYATAZ is 
contraindicated (see section 4.3) 

ANTICOAGULANTS 

Warfarin Co-administration with REYATAZ 
has the potential to increase or 
decrease warfarin concentrations. 

It is recommended that the 
International Normalised Ratio 
(INR) be monitored carefully 
during treatment with 
REYATAZ, especially when 
commencing therapy. 

ANTIEPILEPTICS 



 19 

Carbamazepine REYATAZ may increase plasma 
levels of carbamazepine due to 
CYP3A4 inhibition.  
Due to carbamazepine inducing effect, 
a reduction in REYATAZ exposure 
cannot be ruled out. 

Carbamazepine should be used 
with caution in combination 
with REYATAZ. 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 
REYATAZ exposure cannot be ruled 
out. 

Phenobarbital and phenytoin 
should be used with caution in 
combination with 
REYATAZ/ritonavir. 
 
When REYATAZ/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 
REYATAZ/ritonavir may decrease 
lamotrigine plasma concentrations due 
to UGT1A4 induction. 
 
 

Lamotrigine should be used with 
caution in combination with 
REYATAZ/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 REYATAZ is co-administered 
with irinotecan, patients should 
be closely monitored for adverse 
events related to irinotecan. 

Immunosuppressants 

Cyclosporin 
Tacrolimus 
Sirolimus 
 

Concentrations of these 
immunosuppressants may be increased 
when co-administered with 
REYATAZ 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 
REYATAZ. 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 REYATAZ. 

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 



 20 

Bepridil REYATAZ 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 
REYATAZ/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 REYATAZ due 
to CYP3A4 inhibition. 

Caution should be exercised 
when verapamil is co-
administered with REYATAZ. 

CORTICOSTEROIDS 

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 
REYATAZ/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 



 21 

Sildenafil, tadalafil, vardenafil Sildenafil, tadalafil and vardenafil are 
metabolised by CYP3A4. Co-
administration with REYATAZ 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 
REYATAZ (see section 4.4). 
Also see PULMONARY 
ARTERIAL HYPERTENSION 
in this table for further 
information regarding co-
administration of REYATAZ 
with sildenafil. 

HERBAL PRODUCTS 

St. John’s wort (Hypericum 
perforatum) 

Concomitant use of St. John's wort 
with REYATAZ may be expected to 
result in significant reduction in 
plasma levels of 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). 

Co-administration of 
REYATAZ with products 
containing 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 
REYATAZ/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 
REYATAZ/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. 



 22 

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 
REYATAZ may result in increased 
concentrations.  

Co-administration of simvastatin 
or lovastatin with REYATAZ is 
contraindicated due to an 
increased risk of myopathy 
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 REYATAZ 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 REYATAZ 
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 REYATAZ is not 
recommended (see section 4.4). 

OPIOIDS 



 23 

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 
REYATAZ 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 REYATAZ, based 
on these data. 

No dosage adjustment is 
necessary if methadone is co-
administered with REYATAZ. 

PULMONARY ARTERIAL HYPERTENSION 

PDE5 Inhibitors 

Sildenafil Co-administration with REYATAZ 
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 REYATAZ 
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 



 24 

Midazolam 
Triazolam 

Midazolam and triazolam are 
extensively metabolised by CYP3A4. 
Co-administration with REYATAZ 
may cause a large increase in the 
concentration of these 
benzodiazepines. No drug interaction 
study has been performed for the co-
administration of REYATAZ 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 
REYATAZ with triazolam or 
orally administered midazolam 
is contraindicated 
(see section 4.3), whereas 
caution should be used with co-
administration of REYATAZ 
and parenteral midazolam. If 
REYATAZ 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. 

 
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 REYATAZ without ritonavir may affect atazanavir 

concentrations 
 co-administration of fluticasone and REYATAZ without ritonavir may increase 

fluticasone concentrations relative to fluticasone given alone 
 if an oral contraceptive is administered with REYATAZ 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 REYATAZ with ritonavir may be considered during pregnancy only if 
the potential benefit justifies the potential risk. 
 
In clinical trial AI424-182 REYATAZ/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 REYATAZ/ritonavir 300/100 mg and 13 of 21 (62%) women on 
REYATAZ/ritonavir 400/100 mg experienced grades 3 to 4 hyperbilirubinaemia. There were no cases 
of lactic acidosis observed in the clinical trial AI424-182. 
 



 25 

The study assessed 40 infants who received antiretroviral prophylactic treatment (which did not 
include REYATAZ) 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 REYATAZ/ritonavir 
300/100 mg and four of 20 infants (20%) born to women treated with REYATAZ/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 REYATAZ 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 
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 REYATAZ (see section 4.8).  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
REYATAZ has been evaluated for safety in combination therapy with other antiretroviral medicinal 
products in controlled clinical trials in 1,806 adult patients receiving REYATAZ 400 mg once daily 
(1,151 patients, 52 weeks median duration and 152 weeks maximum duration) or REYATAZ 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 REYATAZ 400 mg once daily and 
patients who received REYATAZ 300 mg with ritonavir 100 mg once daily, except that jaundice and 
elevated total bilirubin levels were reported more frequently with REYATAZ plus ritonavir. 
 
Among patients who received REYATAZ 400 mg once daily or REYATAZ 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 REYATAZ and one or more NRTIs were nausea (20%), 
diarrhoea (10%), and jaundice (13%). Among patients receiving REYATAZ 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 REYATAZ is based on safety data from clinical studies and post-
marketing experience. Frequency is defined using the following convention: very common (≥ 1/10), 



 26 

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 
 

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 
 



 27 

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 REYATAZ 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 REYATAZ.  
 
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 
REYATAZ (see section 4.4). 
 
Laboratory abnormalities 
The most frequently reported laboratory abnormality in patients receiving regimens containing 
REYATAZ 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 REYATAZ 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 REYATAZ 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 REYATAZ 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 REYATAZ experienced concurrent Grade 3-4 ALT/AST and 
Grade 3-4 total bilirubin elevations. 
 
Paediatric population 
In a 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 REYATAZ 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 REYATAZ 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 REYATAZ oral powder of 80 weeks. No deaths were reported. 



 28 

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 
REYATAZ 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 REYATAZ 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 REYATAZ 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, 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 REYATAZ 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 REYATAZ. 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 



 29 

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 REYATAZ/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 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 REYATAZ/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 REYATAZ/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). 
 



 30 

Table 5: Efficacy Outcomes in Study 138 a 

Parameter 

REYATAZ/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 
    <50 cells/mm3 

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

    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 REYATAZ/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 
REYATAZ 300 mg + ritonavir 100 mg once daily and two NRTIs, unboosted REYATAZ 400 mg 
once daily and two NRTIs administered during a 48-week maintenance phase (n=87) had similar 
antiviral efficacy compared with REYATAZ + 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 REYATAZ and two NRTIs compared with 
75% on REYATAZ + ritonavir and two NRTIs. 
 
Eleven subjects (13%) in the unboosted REYATAZ group and 6 (7%) in the REYATAZ + ritonavir 
group, had virologic rebound. Four subjects in the unboosted REYATAZ group and 2 in the 
REYATAZ + 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 REYATAZ and 1 subject in the REYATAZ + ritonavir group. 
 
There were fewer treatment discontinuations in the unboosted REYATAZ group (1 vs. 4 subjects in 
the REYATAZ + ritonavir group). There was less hyperbilirubinaemia and jaundice in the unboosted 
REYATAZ group compared with the REYATAZ + ritonavir group (18 and 28 subjects, respectively). 



 31 

 
In antiretroviral experienced adult patients 
Study 045 is a randomised, multicenter trial comparing REYATAZ/ritonavir (300/100 mg once daily) 
and REYATAZ/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 REYATAZ + ritonavir treatment arm 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 REYATAZ + 
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 REYATAZ + 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 REYATAZ + 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 REYATAZ + 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. 



 32 

 
REYATAZ + saquinavir was shown to be inferior to lopinavir + ritonavir. 
 
Paediatric population 
Assessment of the pharmacokinetics, safety, tolerability, and efficacy of REYATAZ 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 REYATAZ (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 
REYATAZ 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 
REYATAZ 

Capsules/ritonavir 
(300 mg/100 mg once 

daily) n=16 

Treatment-
Experienced 
REYATAZ 

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 
 
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 REYATAZ 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.  
 



 33 

In HIV-infected patients (n=13), multiple dosing of REYATAZ 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 REYATAZ and ritonavir with food optimises the bioavailability of 
atazanavir. Co-administration of a single 300 mg dose of REYATAZ 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 
REYATAZ 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, REYATAZ 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.  
 
Metabolism: 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: in healthy subjects, the renal elimination of unchanged atazanavir was 
approximately 7% of the administered dose. There are no pharmacokinetic data available for 
REYATAZ with ritonavir in patients with renal insufficiency. REYATAZ (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. REYATAZ 
(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). 
 



 34 

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 REYATAZ 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, Cmax and AUC) in paediatric patients are expected to be similar to those 
observed in adults.  
 
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). 



 35 

 
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 
 
REYATAZ 100 mg hard capsules 
Capsule contents: crospovidone, lactose monohydrate and magnesium stearate 
 
Capsule shells: gelatine, indigocarmin (E132) and titanium dioxide (E171) 
 
Blue ink containing: shellac, propylene glycol, ammonium hydroxide and indigocarmin (E132) 
 
White ink containing: shellac, titanium dioxide (E171), ammonium hydroxide, propylene glycol and 
simethicone 
 
REYATAZ 150 mg hard capsules 
Capsule contents: crospovidone, lactose monohydrate and magnesium stearate 
 
Capsule shells: gelatine, indigocarmin (E132) and titanium dioxide (E171) 
 
Blue ink containing: shellac, propylene glycol, ammonium hydroxide and indigocarmin (E132) 
 
White ink containing: shellac, titanium dioxide (E171), ammonium hydroxide, propylene glycol and 
simethicone 
 
REYATAZ 200 mg hard capsules 
Capsule contents: crospovidone, lactose monohydrate and magnesium stearate 
 
Capsule shells: gelatine, indigocarmin (E132) and titanium dioxide (E171) 
 
White ink containing: shellac, titanium dioxide (E171), ammonium hydroxide, propylene glycol and 
simethicone 
 



 36 

REYATAZ 300 mg hard capsules 
Capsule contents: crospovidone, lactose monohydrate and magnesium stearate 
 
Capsule shells: gelatine, red iron oxide, black iron oxide, yellow iron oxide, indigocarmin (E132) and 
titanium dioxide (E171) 
 
White ink containing: shellac, titanium dioxide (E171), ammonium hydroxide, propylene glycol and 
simethicone 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
 
6.5 Nature and contents of container 
 
REYATAZ 100 mg hard capsules 
Each carton contains one high-density polyethylene (HDPE) bottle closed with child-resistant 
polypropylene closure. Each bottle contains 60 hard capsules. 
 
Each carton contains 60 x 1 capsules; 10 blister cards of 6 x 1 capsules each in Alu/Alu perforated unit 
dose blisters. 
 
REYATAZ 150 mg hard capsules 
Each carton contains one high-density polyethylene (HDPE) bottle closed with child-resistant 
polypropylene closure. Each bottle contains 60 hard capsules. 
 
Each carton contains 60 x 1 capsules; 10 blister cards of 6 x 1 capsules each in Alu/Alu perforated unit 
dose blisters. 
 
REYATAZ 200 mg hard capsules 
Each carton contains one high-density polyethylene (HDPE) bottle or three high-density polyethylene 
(HDPE) bottles closed with child-resistant polypropylene closure. Each bottle contains 60 hard 
capsules. 
 
Each carton contains 60 x 1 capsules; 10 blister cards of 6 x 1 capsules each in Alu/Alu perforated unit 
dose blisters. 
 
REYATAZ 300 mg hard capsules 
Each carton contains one high-density polyethylene (HDPE) bottle or three high-density polyethylene 
(HDPE) bottles closed with child-resistant polypropylene closure. Each bottle contains 30 hard 
capsules. 
 
Each carton contains 30 x 1 capsules; 5 blister cards of 6 x 1 capsules each in Alu/Alu perforated unit 
dose blisters. 
 
Not all pack sizes may be marketed. 
 



 37 

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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/267/001-006; 008-011 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 March 2004 
Date of latest renewal: 02 March 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



 38 

1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 50 mg oral powder 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sachet of 1.5 g oral powder contains 50 mg of atazanavir (as sulphate). 
 
Excipient with known effect: 63 mg of aspartame; 1305.15 mg of sucrose per sachet (1.5 g oral 
powder). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oral powder 
Off white to pale yellow powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
REYATAZ oral powder, co-administered with low dose ritonavir, is indicated in combination with 
other antiretroviral medicinal products for the treatment of HIV-1 infected paediatric patients at least 
3 months of age and weighing at least 5 kg (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 REYATAZ 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 
Paediatric patients (at least 3 months of age and weighing at least 5 kg) 
The doses of atazanavir oral powder and ritonavir for paediatric patients are based on body weight as 
shown in Table 1. REYATAZ oral powder must be taken with ritonavir and has to be taken with food. 
 
Table 1: Dose of REYATAZ oral powder with ritonavir for paediatric patientsa (at least 
3 months of age and weighing at least 5 kg)  
Body weight (kg) REYATAZ once daily dose  ritonavir once daily dose 
at least 5 to less than 15 200 mg (4 sachetsb) 80 mgc 
at least 15 to less than 35 250 mg (5 sachetsb) 80 mgc 
at least 35  300 mg (6 sachetsb) 100 mgd 
a The same recommendations regarding the timing and maximum doses of concomitant proton pump inhibitors and H2-
receptor antagonists in adults also apply to paediatric patients (see section 4.5). 
b Each sachet contains 50 mg of atazanavir.  

c Ritonavir oral solution. 
d Ritonavir oral solution or capsule/tablet. 
 
REYATAZ capsules are available for paediatric patients at least 6 years of age who weigh at least 
15 kg and who are able to swallow capsules (see Summary of Product Characteristics for REYATAZ 



 39 

capsules). Switching from REYATAZ oral powder to REYATAZ capsules 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 Summary of Product Characteristics for REYATAZ capsules). 
 
Special populations 
Renal impairment 
No dosage adjustment is needed. REYATAZ with ritonavir is not recommended in patients 
undergoing haemodialysis (see sections 4.4 and 5.2). 
 
Hepatic impairment 
REYATAZ with ritonavir has not been studied in patients with hepatic impairment. REYATAZ with 
ritonavir should be used with caution in patients with mild hepatic impairment. REYATAZ must not 
be used in patients with moderate to severe hepatic impairment (see sections 4.3, 4.4, and 5.2). 
 
Pregnancy and Postpartum 
During the second and third trimesters of pregnancy: 
REYATAZ 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 REYATAZ 

400 mg with ritonavir 100 mg with TDM may be considered (see sections 4.6 and 5.2). 
 It is not recommended to use REYATAZ with ritonavir for pregnant patients who are receiving 

both tenofovir disoproxil and an H2-receptor antagonist. 
 
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) 
REYATAZ has not been studied in children less than 3 months of age and is not recommended 
because of the potential risk of kernicterus. 
 
Method of administration 
For oral use.  
REYATAZ oral powder should be taken/given with food (e.g. applesauce or yogurt) or drinks (e.g. 
milk, infant formula or water) for infants who can drink from a cup. For young infants (less than 
6 months) who cannot eat solid food or drink from a cup, REYATAZ oral powder should be mixed 
with infant formula and given using an oral syringe, which can be obtained from a pharmacist. 
Administration of REYATAZ and infant formula using an infant bottle is not recommended because 
the full dose may not be delivered. 
 
For details on preparation and administration of the REYATAZ oral powder and Instructions for Use, 
see section 6.6. 
 



 40 

4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Patients with moderate to severe hepatic insufficiency (see sections 4.2 and 4.4). 
 
Co-administration with simvastatin or lovastatin (see section 4.5). 
 
Combination of rifampicin with concomitant low-dose ritonavir (see section 4.5). 
 
Co-administration 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, alfuzosin, astemizole, terfenadine, 
cisapride, pimozide, quinidine, lurasidone, 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 REYATAZ 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 REYATAZ 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  



 41 

No dosage adjustment is needed in patients with renal impairment. However, REYATAZ with 
ritonavir is not recommended in patients undergoing haemodialysis (see sections 4.2 and 5.2). 
 
QT prolongation 
Dose related asymptomatic prolongations in PR interval with REYATAZ 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), REYATAZ should be used with caution and only if the benefits exceed the risk 
(see section 5.1). Particular caution should be used when prescribing REYATAZ 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, REYATAZ (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 REYATAZ (see section 4.8). Hepatic 
transaminase elevations that occur with elevated bilirubin in patients receiving REYATAZ should be 
evaluated for alternative aetiologies. Alternative antiretroviral therapy to REYATAZ 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 REYATAZ and indinavir have not been studied and co-administration of these 
medicinal products is not recommended (see section 4.5). 
 
Cholelithiasis 
Cholelithiasis has been reported in patients receiving REYATAZ (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 



 42 

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 REYATAZ (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 occurs 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 REYATAZ.  
 
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 
REYATAZ. Patients should be advised of the signs and symptoms and monitored closely for skin 
reactions. REYATAZ 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 
REYATAZ, REYATAZ may not be restarted. 
 
Interactions with other medicinal products 
The combination of REYATAZ with atorvastatin is not recommended (see section 4.5). 
 
Co-administration of REYATAZ with nevirapine or efavirenz is not recommended (see section 4.5). 
If the co-administration of REYATAZ with an NNRTI is required, an increase in the dose of both 
REYATAZ 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 REYATAZ with ritonavir 
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 REYATAZ with concomitant low-dose ritonavir. Co-administration 
of REYATAZ 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). 



 43 

 
Co-administration of voriconazole and REYATAZ 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 REYATAZ/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 REYATAZ/ritonavir may result in increased cardiovascular 
adverse events associated with salmeterol. Co-administration of salmeterol and REYATAZ 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 REYATAZ with proton pump inhibitors is not recommended (see section 4.5). If 
the combination of REYATAZ with a proton pump inhibitor is judged unavoidable, close clinical 
monitoring is recommended in combination with an increase in the dose of REYATAZ 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 REYATAZ/ritonavir with other hormonal contraceptives or oral contraceptives 
containing progestogens other than norgestimate has not been studied, and therefore should be avoided 
(see section 4.5). 
 
Paediatric population 
Safety 
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), REYATAZ 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 
Phenylketonuria 
REYATAZ oral powder contains aspartame as a sweetening agent. Aspartame provides a source of 
phenylalanine and, therefore, may not be suitable for persons with phenylketonuria. 
 
Diabetic population 
REYATAZ oral powder contains 1305.15 mg of sucrose per sachet. For the recommended paediatric 
dosage, REYATAZ oral powder contains 3915.45 mg sucrose per 150 mg atazanavir, 5220.60 mg 
sucrose per 200 mg atazanavir, 6525.75 mg sucrose per 250 mg atazanavir, and 7830.90 mg sucrose 
per 300 mg atazanavir. This should be taken into account in patients with diabetes mellitus. Patients 
with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase 
isomaltase insufficiency should not take this medicine. 
 



 44 

4.5 Interaction with other medicinal products and other forms of interaction 
 
When REYATAZ 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 
REYATAZ and ritonavir. 
 
Atazanavir is metabolised in the liver through CYP3A4. It inhibits CYP3A4. Therefore, REYATAZ 
with ritonavir 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 REYATAZ 
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 REYATAZ 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/ritonavir and protease inhibitors, antiretroviral agents other than 
protease inhibitors, and other non-antiretroviral 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 approved regimen of atazanavir. 
 
Table 2: Interactions between REYATAZ and other medicinal products 
 

Medicinal products by 
therapeutic area 

Interaction Recommendations concerning 
co-administration 

ANTI-HCV AGENTS 

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 
REYATAZ 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). 



 45 

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%) 
 
*Lack of pharmacokinetics interaction 
bounds 70-143% 
 
Effect on atazanavir and ritonavir 
exposure has not been studied. 
Expected: 
↔ Atazanavir  
↔ Ritonavir  
 
The mechanism of interaction between 
REYATAZ/ritonavir and 
sofosbuvir/velpatasvir/voxilaprevir is 
inhibition of OATP1B, Pgp, and 
CYP3A. 

Co-administration of 
REYATAZ with voxilaprevir-
containing products is expected 
to increase the concentration of 
voxilaprevir. Co-administration 
of REYATAZ with 
voxilaprevir-containing 
regimens is not recommended. 

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 
REYATAZ with 
glecaprevir/pibrentasvir 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 



 46 

Protease inhibitors: The co-administration of REYATAZ/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 
REYATAZ/ritonavir 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 
REYATAZ/ritonavir with these 
medicinal products is not 
expected to significantly alter 
the exposure of the co-
administered medicinal 
products. 

Abacavir The co-administration of REYATAZ/ 
ritonavir with abacavir is not expected 
to significantly alter the exposure of 
abacavir. 

 



 47 

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 
REYATAZ/ritonavir taken with 
food. The co-administration of 
REYATAZ/ritonavir with 
stavudine 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. 
 
Studies conducted in HIV-
infected patients 
 

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 300 mg 
(n=39) was compared to 
atazanavir/ritonavir 300/100 mg 
(n=33). 
 
The efficacy of REYATAZ/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. 

 



 48 

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-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 
with REYATAZ/ritonavir 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 REYATAZ 
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%) * 
Atazanavir Cmax ↔2% (↓15% ↑24%) * 
Atazanavir Cmin ↓59% (↓73% ↓40%) * 
 
* When compared to REYATAZ 
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. 

Co-administration of nevirapine 
with REYATAZ/ritonavir is not 
recommended (see section 4.4) 

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 



 49 

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%) 
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. 
 

No recommendation regarding 
dose reduction can be made; 
therefore, caution should be 
exercised if 
REYATAZ/ritonavir is co-
administered with 
clarithromycin. 

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 
REYATAZ/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. 



 50 

 Based on data obtained with other 
boosted PIs and ketoconazole, where 
ketoconazole AUC showed a 3-fold 
increase, REYATAZ/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 
REYATAZ/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 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. 

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%) 
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.  
 

Fluconazole 200 mg once daily 
(atazanavir 300 mg and 
ritonavir 100 mg once daily) 

Atazanavir and fluconazole 
concentrations were not significantly 
modified when REYATAZ/ritonavir 
was co-administered with fluconazole. 

No dosage adjustments are 
needed for REYATAZ/ritonavir 
and fluconazole. 

ANTIMYCOBACTERIAL 



 51 

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 
REYATAZ/ritonavir, 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 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 REYATAZ/ritonavir. 

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 
REYATAZ or other protease inhibitors 
with ritonavir, a high frequency of 
liver reactions was seen. 

The combination of rifampicin 
and REYATAZ with 
concomitant low-dose ritonavir 
is contraindicated (see 
section 4.3). 

ANTIPSYCHOTICS 

Quetiapine Due to CYP3A4 inhibition by 
REYATAZ, concentrations of 
quetiapine are expected to increase. 

Co-administration of 
REYATAZ/ritonavir with 
quetiapine is contraindicated as 
may increase quetiapine-related 
toxicity. Increased plasma 
concentrations of quetiapine 
may lead to coma 
(see section 4.3). 

Lurasidone REYATAZ is expected to increase 
plasma levels of lurasidone due to 
CYP3A4 inhibition. 

Co-administration of lurasidone 
with REYATAZ is 
contraindicated as this may 
incrrease 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 REYATAZ 



 52 

Famotidine 20 mg twice daily Atazanavir AUC ↓18% (↓25% ↑1%) 
Atazanavir Cmax ↓20% (↓32% ↓7%) 
Atazanavir Cmin ↔1% (↓16% ↑18%) 

300 mg/ritonavir 100 mg and 
H2-receptor antagonists are co-
administered, a dose equivalent 
to famotidine 20 mg twice daily 
should not be exceeded. If a 
higher dose of an H2-receptor 
antagonist is required (eg, 
famotidine 40 mg twice daily or 
equivalent) an increase of the 
REYATAZ/ritonavir dose from 
300/100 mg to 400/100 mg can 
be considered. 

Famotidine 40 mg twice daily Atazanavir AUC ↓23% (↓32% ↓14%) 
Atazanavir Cmax ↓23% (↓33% ↓12%) 
Atazanavir Cmin ↓20% (↓31% ↓8%) 

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 REYATAZ/ritonavir with 
both tenofovir disoproxil and an 
H2-receptor antagonist are co-
administered,a dose increase of 
REYATAZ 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, 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 

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 
REYATAZ/ritonavir with 
proton pump inhibitors is not 
recommended. If the 
combination of 



 53 

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 REYATAZ/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. 
 

REYATAZ/ritonavir with a 
proton pump inhibitor is judged 
unavoidable, close clinical 
monitoring is recommended in 
combination with an increase in 
the dose of REYATAZ 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). 

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 
REYATAZ/ritonavir.  

REYATAZ/ritonavir 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/ritonavir. 

Co-administration of 
REYATAZ/ritonavir with 
alfuzosin is contraindicated (see 
section 4.3) 

ANTICOAGULANTS 

Warfarin Co-administration with 
REYATAZ/ritonavir has the potential 
to produce a decrease or, less often, an 
increase in INR (International 
Normalised Ratio).  

It is recommended that the INR 
be monitored carefully during 
treatment with 
REYATAZ/ritonavir, especially 
when commencing therapy. 

ANTIEPILEPTICS 

Carbamazepine REYATAZ/ritonavir may increase 
plasma levels of carbamazepine due to 
CYP3A4 inhibition.  
Due to carbamazepine inducing effect, 
a reduction in REYATAZ/ritonavir 
exposure cannot be ruled out. 

Carbamazepine should be used 
with caution in combination 
with REYATAZ/ritonavir. If 
necessary, monitor 
carbamazepine serum 
concentrations and adjust the 
dose accordingly. Close 
monitoring of the patient's 
virologic response should be 
excercised.  



 54 

Phenytoin, phenobarbital Ritonavir may decrease plasma levels 
of phenytoin and/or phenobarbital due 
to CYP2C9 and CYP2C19 induction. 
Due to phenitoine/phenobarbital 
inducing effect, a reduction in 
REYATAZ/ritonavir exposure cannot 
be ruled out 

Phenobarbital and phenytoin 
should be used with caution in 
combination with 
REYATAZ/ritonavir. 
 
When REYATAZ/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 
REYATAZ/ritonavir may decrease 
lamotrigine plasma concentrations due 
to UGT1A4 induction. 

Lamotrigine should be used with 
caution in combination with 
REYATAZ/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 REYATAZ/ritonavir is co-
administered with irinotecan, 
patients should be closely 
monitored for adverse events 
related to irinotecan. 

Immunosuppressants 

Cyclosporin 
Tacrolimus 
Sirolimus 
 

Concentrations of these 
immunosuppressants may be increased 
when co-administered with 
REYATAZ/ritonavir 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 
REYATAZ/ritonavir. 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 
REYATAZ/ritonavir. 

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 REYATAZ/ritonavir 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) 



 55 

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 
REYATAZ/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 
REYATAZ/ritonavir due to CYP3A4 
inhibition. 

Caution should be exercised 
when verapamil is co-
administered with 
REYATAZ/ritonavir. 

CORTICOSTEROIDS 

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 
REYATAZ/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 



 56 

Sildenafil, tadalafil, vardenafil Sildenafil, tadalafil, and vardenafil are 
metabolised by CYP3A4. Co-
administration with 
REYATAZ/ritonavir 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 
REYATAZ/ritonavir (see 
section 4.4). 
Also see PULMONARY 
ATERIAL HYPERTENSION in 
this table for further information 
regarding co-administration of 
REYATAZ/ritonavir with 
sildenafil. 

HERBAL PRODUCTS 

St. John’s wort (Hypericum 
perforatum) 

Concomitant use of St. John's wort 
with REYATAZ/ritonavir may be 
expected to result in significant 
reduction in plasma levels of 
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). 

Co-administration of 
REYATAZ/ritonavir with 
products containing 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 
REYATAZ/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 
REYATAZ/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. 

LIPID LOWERING AGENTS 

HMG-CoA reductase inhibitors 



 57 

Simvastatin 
Lovastatin 

Simvastatin and lovastatin are highly 
dependent on CYP3A4 for their 
metabolism and co-administration with 
REYATAZ/ritonavir may result in 
increased concentrations.  

Co-administration of simvastatin 
or lovastatin with REYATAZ is 
contraindicated due to an 
increased risk of myopathy 
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 REYATAZ 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 
REYATAZ/ritonavir may result in 
increased concentrations of salmeterol 
and an increase in salmeterol-
associated adverse events. 
 
The mechanism of interaction is 
CYP3A4 inhibition by 
atazanavir/ritonavir. 

Co-administration of salmeterol 
with REYATAZ/ritonavir 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 were not 
significantly affected. 

Co-administration 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 REYATAZ and 
ritonavir, based on these data. 

No dosage adjustment is 
necessary if methadone is co-
administered with REYATAZ 
and ritonavir. 

PULMONARY ARTERIAL HYPERTENSION 

PDE5 Inhibitors 



 58 

Sildenafil Co-administration with 
REYATAZ/ritonavir 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/ritonavir. 
 

A safe and effective dose in 
combination with 
REYATAZ/ritonavir 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 
REYATAZ/ritonavir may cause a 
large increase in the concentration of 
these benzodiazepines. No drug 
interaction study has been performed 
for the co-administration of 
REYATAZ/ritonavir 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. 

REYATAZ/ritonavir should not 
be co-administered with 
triazolam or orally administered 
midazolam (see section 4.3), 
whereas caution should be used 
with co-administration of 
REYATAZ/ritonavir and 
parenteral midazolam. If 
REYATAZ 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. 

 
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 REYATAZ may be considered during pregnancy only if the potential benefit 
justifies the potential risk. 
 
In clinical trial AI424-182 REYATAZ/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 REYATAZ/ritonavir 300/100 mg and 13 of 21 (62%) women on 
REYATAZ/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 REYATAZ) 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 REYATAZ/ritonavir 
300/100 mg and four of 20 infants (20%) born to women treated with REYATAZ/ritonavir 
400/100 mg experienced grade 3-4 bilirubin. There was no evidence of pathologic jaundice and six of 



 59 

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 REYATAZ 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 
In a non-clinical 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 REYATAZ (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
REYATAZ has been evaluated for safety in combination therapy with other antiretroviral medicinal 
products in controlled clinical trials in 1,806 adult patients receiving REYATAZ 400 mg once daily 
(1,151 patients, 52 weeks median duration and 152 weeks maximum duration) or REYATAZ 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 REYATAZ 400 mg once daily and 
patients who received REYATAZ 300 mg with ritonavir 100 mg once daily, except that jaundice and 
elevated total bilirubin levels were reported more frequently with REYATAZ plus ritonavir. 
 
Among patients who received REYATAZ 400 mg once daily or REYATAZ 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 REYATAZ and one or more NRTIs were nausea (20%), 
diarrhoea (10%), and jaundice (13%). Among patients receiving REYATAZ 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 REYATAZ 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 



 60 

 
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 
 

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 REYATAZ 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 



 61 

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 REYATAZ.  
 
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 
REYATAZ (see section 4.4). 
 
Laboratory abnormalities 
The most frequently reported laboratory abnormality in patients receiving regimens containing 
REYATAZ 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 REYATAZ 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 REYATAZ 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 REYATAZ 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 REYATAZ experienced concurrent Grade 3-4 ALT/AST and 
Grade 3-4 total bilirubin elevations. 
 
Paediatric population 
In a 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 REYATAZ 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 abnormalities in paediatric patients 
receiving REYATAZ 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 REYATAZ 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 
REYATAZ 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. 



 62 

 
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 REYATAZ 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 REYATAZ 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, 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 REYATAZ 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 REYATAZ. 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 



 63 

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 REYATAZ/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 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 
883 antiretroviral treatment naive patients comparing REYATAZ/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 
REYATAZ/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). 
 
The 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). The 
REYATAZ/ritonavir arm has 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: 78% of patients on REYATAZ/ritonavir compared to 76% on lopinavir/ritonavir (difference 
estimate of ATV/RTV-LPV/RTV: 1.7% [95% CI, -3.8%, 7.1%] according to the Confirmed Virologic 
Response (CVR) Non-Completer = Failure (NC = F) definition of response. 
 



 64 

In a per protocol analysis which excluded non-completers (i.e. patients who discontinued before the 
week 48 HIV RNA assessment) and patients with major protocol deviations, the proportion of patients 
with HIV RNA < 50 copies/ml at week 48 was 86% (338/392) for REYATAZ/ritonavir and 89% 
(332/372) for lopinavir/ritonavir (difference estimate of ATV/RTV-LPV/RTV: -3% [95% CI, -7.6%, 
1.5%]. 
 
Table 5: Efficacy Outcomes in Study 138 a 

Parameter 

REYATAZ/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 
    <50 cells/mm3 

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

    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 REYATAZ/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. 
 
In antiretroviral experienced adult patients 
Study 045 is a randomised, multicenter trial comparing REYATAZ/ritonavir (300/100 mg once daily) 
and REYATAZ/saquinavir (400/1,200 mg once daily), to lopinavir + ritonavir (400/100 mg fixed dose 
combination twice daily), each in combination with tenofovi 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 REYATAZ + ritonavir treatment arm 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). 



 65 

 
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 REYATAZ + 
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 REYATAZ + 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 REYATAZ + 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 REYATAZ + 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. 
 
REYATAZ + saquinavir was shown to be inferior to lopinavir + ritonavir. 
 
Paediatric population 
Paediatric trials with REYATAZ capsules 
Assessment of the pharmacokinetics, safety, tolerability, and efficacy of REYATAZ 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 REYATAZ (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 capsules (with 
or without ritonavir) in children below 6 years of age. 
 



 66 

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

Capsules/ritonavir 
(300 mg/100 mg once 

daily) n=16 

Treatment-
Experienced 
REYATAZ 

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. 
 
Paediatric trials with REYATAZ oral powder 
Assessment of the pharmacokinetics, safety, tolerability, and virologic response of REYATAZ oral 
powder was based on data from two open-label, multicenter clinical trials. 
 AI424-397 (PRINCE I): In paediatric patients from 3 months to less than 6 years of age 
 AI424-451 (PRINCE II): In paediatric patients from 3 months to less than 11 years of age 

In these studies, 155 patients (59 antiretroviral-naive and 96 antiretroviral-experienced) received once 
daily REYATAZ oral powder and ritonavir, in combination with two NRTIs. 
 
For inclusion in both trials, treatment-naive patients had to have genotypic sensitivity to REYATAZ 
and two NRTIs, and treatment-experienced patients had to have documented genotypic and phenotypic 
sensitivity at screening to REYATAZ and at least 2 NRTIs. Patients exposed only to antiretrovirals in 
utero or intrapartum were considered treatment-naive. Patients who received REYATAZ or 
REYATAZ/ritonavir at any time prior to study enrollment or who had a history of treatment failure on 
two or more protease inhibitors, protease inhibitor resistance or evidence of pre-existing cardiac 
abnormalities were excluded from the trials. Protease inhibitor resistance was defined as genotypic 
resistance to atazanavir or either component of the local NRTI backbone based on the criteria of 1) any 
major mutations: I50L, I84V, N88S and 2) ≥ 2 of the following minor or cross resistant mutations: 
M46I/L, G48V, I54L/V/M/T/A, V82A/T/FI, L90M, V32I. 
 
At Week 48 there were 134 paediatric patients aged 3 months to less than 11 years that received 
REYATAZ oral powder with ritonavir that were evaluated for efficacy. These data are presented in 
Table 8. For treatment-naive paediatric patients, the mean baseline CD4 cell count was 930 cells/mm3 
(range: 46 to 2291 cells/mm3) and mean baseline plasma HIV-1 RNA was 4.81 log10 copies/ml (range: 
3.4 to 5.9 log10 copies/ml). For treatment-experienced paediatric patients, the mean baseline CD4 cell 



 67 

count was 1441 cells/mm3 (range: 84 to 5703 cells/mm3) and mean baseline plasma HIV-1 RNA was 
4.67 log10 copies/ml (range: 2.0 to 5.9 log10 copies/ml). 
 
Table 8: Efficacy Outcomes for oral powder (paediatric patients at least 3 months of age and 
weighing at least 5 kg) at Week 48 (Studies AI424-397 and AI424-451) 

Parameter  
Treatment-Naive 

REYATAZ 
Powder/ritonavir n=52 

Treatment-Experienced 
REYATAZ 

Powder/ritonavir n=82 
HIV RNA <50 copies/ml, %a  
at least 5 to < 10 kg (REYATAZ 
150 and 200 mg)  
at least 10 to < 15 kg 
at least 15 to < 25 kg 
at least 25 to < 35 kg 

33 (4/12) 
 

59 (13/22) 
61 (11/18) 

- 

52 (17/33) 
 

35 (6/17) 
57 (17/30) 
50.0 (1/2) 

HIV RNA <400 copies/ml, %a  
at least 5 to < 10 kg (REYATAZ 
150 and 200 mg)  
at least 10 to < 15 kg 
at least 15 to < 25 kg 
at least 25 to < 35 kg 

75 (9/12) 
 

82 (18/22) 
78 (14/18) 

- 

61 (20/33) 
 

59 (10/17) 
67 (20/30) 
50.0 (1/2) 

CD4 Mean Change from Baseline, cells/mm3  
at least 5 to < 10 kg (REYATAZ 
150 and 200 mg)  
at least 10 to < 15 kg 
at least 15 to < 25 kg 
at least 25 to < 35 kg 

293 (n=7) 
 

293 (n=11) 
305 (n=9) 

- 

63 (n=16) 
 

307 (n=8) 
374 (n=12) 
213 (n=1) 

a Intent-to-treat analysis, with missing values considered as failures. 
 
5.2 Pharmacokinetic properties 
 
Absorption: in HIV-infected patients (n=33, combined studies), multiple dosing of REYATAZ 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.  
 
Food effect: co-administration of REYATAZ and ritonavir with food optimises the bioavailability of 
atazanavir. Co-administration of a single 300 mg dose of REYATAZ 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 
REYATAZ 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, REYATAZ 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.  
 
Metabolism: 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 



 68 

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. 
 
Linearity/non-linearity: 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. 
 
Special populations 
 
Renal impairment: in healthy subjects, the renal elimination of unchanged atazanavir was 
approximately 7% of the administered dose. There are no pharmacokinetic data available for 
REYATAZ with ritonavir in patients with renal insufficiency. REYATAZ (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. 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 REYATAZ capsules with 
ritonavir are presented in Table 9. 
 



 69 

Table 9: 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, Cmax and AUC) in paediatric patients are expected to be similar to those 
observed in adults. 
 
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. 
 



 70 

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 
 
Aspartame (E951) 
Sucrose 
Orange vanilla flavour 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
After mixing with food or beverage, mixture may be stored for up to 1 hour at temperatures not 
above 30°C. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions.  
 
REYATAZ oral powder should be stored in the original sachet and should not be opened until ready to 
use.  
 
For storage conditions after mixing of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Polyester film/Aluminum/Polyethylene sealant film sachet.  
 
Each carton contains 30 sachets. 
 
6.6 Special precautions for disposal and other handling 
 
Instructions for use: 
The dose and the number of REYATAZ oral powder sachets needed is determined based on weight 
(see section 4.2.). 

1. Prior to mixing, the sachet is tapped to settle the powder. A clean pair of scissors is used to cut 
each sachet along the dotted line. 



 71 

2. The appropriate option listed below is chosen for mixing and administration with liquid infant 
formula, beverage or food. Larger volumes or quantities of liquid infant formula, beverage or 
food may be used for dosing. It should be ensured that the patient eats or drinks all the infant 
formula, beverage or food that contains the powder. 

A: To mix the recommended number of REYATAZ oral powder sachets with liquid infant 
formula in a small medicine cup or small container and to administer with an oral syringe, which 
can be obtained from a pharmacist: 

 A spoon is used to mix the content of the appropriate number of sachets (4 or 5 
sachets depending on infant weight) with 10 ml of prepared liquid infant formula in 
the medicine cup or small container. The full amount of the mixture is drawn up into 
an oral syringe and administered into either right or left inner cheek of the infant. 
Another 10 ml of formula is poured into the medicine cup or small container to rinse 
off remaining REYATAZ oral powder in the cup or container. The residual mixture is 
drawn up into the syringe and administered into either the right or left inner cheek of 
the infant. 

B: To mix the recommended number of REYATAZ oral powder sachets with a beverage such as 
milk or water in a small drinking cup:  

 A spoon is used to mix the content of the sachets with 30 ml of the beverage. The 
child is to drink the mixture. An additional 15 ml of beverage is added to the drinking 
cup for thorough rinsing of the cup and contents are mixed. The child is to drink the 
entire residual mixture.  

 If water is used, food should also be taken at the same time. 
C: To mix the recommended number of REYATAZ oral powder sachets with food such as 
applesauce or yogurt in a small container: 

 One tablespoon of food is used to mix the content of the sachets. The mixture is fed to 
the infant or young child. An additional tablespoon of food is added to the small 
container for thorough delivery of the powder from the container and contents are 
mixed.The entire residual mixture is fed to the child. 

3. The entire dosage of REYATAZ oral powder (mixed in the liquid infant formula, beverage or 
food) is administered within one hour of preparation (the mixture can be left at room stored at 
temperatures not above 30°C during this period). 

4. Additional infant formula, beverage or food may be given after consumption of the entire 
mixture. 

5. Ritonavir is administered immediately following REYATAZ powder administration. 
 
For further details on the preparation and administration of the REYATAZ oral powder, see the 
Patient Information Leaflet, Instructions for Use section 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/267/012 
 
 



 72 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 March 2004 
Date of latest renewal: 02 March 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
  



 73 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER 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 
 



 74 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Bristol-Myers Squibb S.r.l., Contrada Fontana del Ceraso, 03012 Anagni (FR), Italy 
 
Swords Laboratories T/A Lawrence Laboratories, Unit 12, The Distribution Centre, Shannon 
Industrial Estate, Shannon, Co. Clare, Ireland 
 
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. 

 
 
  



 75 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 76 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 77 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON TEXT (BOTTLE AND BLISTER PRESENTATIONS) AND BOTTLE 
LABEL TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 100 mg hard capsules 
atazanavir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 100 mg of atazanavir (as sulphate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: contains lactose (see leaflet for further information). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Carton and label bottle pack (1 bottle): 60 hard capsules 
 
Blister pack: 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 {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Bottle pack: 
Do not store above 25°C. 
 



 78 

Blister pack: 
Do not store above 25°C. 
Store in the original package 
 
 
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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Bottle pack  
60 hard capsules: EU/1/03/267/001 
 
Blister pack : 
60 hard capsules: EU/1/03/267/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: REYATAZ 100 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  



 79 

<NN>:  



 80 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 100 mg hard capsules 
atazanavir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 81 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON TEXT (BOTTLE AND BLISTER PRESENTATIONS) AND BOTTLE 
LABEL TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 150 mg hard capsules 
atazanavir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 150 mg of atazanavir (as sulphate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: contains lactose (see leaflet for further information). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Carton and label bottle pack (1 bottle): 60 hard capsules 
 
Blister pack: 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 {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Bottle pack: 
Do not store above 25°C. 
 



 82 

Blister pack: 
Do not store above 25°C. 
Store in the original package 
 
 
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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Bottle pack  
60 hard capsules: EU/1/03/267/003 
 
Blister pack : 
60 hard capsules: EU/1/03/267/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: REYATAZ 150 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  



 83 

<NN>:  
 



 84 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 150 mg hard capsules 
atazanavir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 85 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON TEXT (BOTTLE AND BLISTER PRESENTATIONS) AND BOTTLE 
LABEL TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 200 mg hard capsules 
atazanavir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 200 mg of atazanavir (as sulphate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: contains lactose (see leaflet for further information). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Carton Bottle pack (1 bottle): 60 hard capsules 
Carton Bottle pack: (3 bottles): 3 x 60 hard capsules (3 bottles of 60 hard capsules) 
Label Bottle pack: 60 hard capsules 
 
Blister pack: 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 {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Bottle pack: 



 86 

Do not store above 25°C. 
 
Blister pack: 
Do not store above 25°C. 
Store in the original package 
 
 
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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Bottle pack  
60 hard capsules: EU/1/03/267/005 
3 x 60 hard capsules: EU/1/03/267/011 
 
Blister pack : 
60 hard capsules: EU/1/03/267/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: REYATAZ 200 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



 87 

 
PC:  
SN:  
<NN>:  
 



 88 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 200 mg hard capsules 
atazanavir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



 89 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON TEXT (BOTTLE AND BLISTER PRESENTATIONS) AND BOTTLE 
LABEL TEXT 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 300 mg hard capsules 
atazanavir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 300 mg of atazanavir (as sulphate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: contains lactose (see leaflet for further information). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Carton Bottle pack (1 bottle): 30 hard capsules 
Carton Bottle pack: (3 bottles): 3 x 30 hard capsules (3 bottles of 30 hard capsules) 
Label Bottle pack: 30 hard capsules  
 
Blister pack: 30 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 {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Bottle pack: 



 90 

Do not store above 25°C. 
 
Blister pack: 
Do not store above 25°C. 
Store in the original package 
 
 
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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Bottle pack  
30 hard capsules: EU/1/03/267/008 
3 x 30 hard capsules: EU/1/03/267/010 
 
Blister pack : 
30 hard capsules: EU/1/03/267/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: REYATAZ 300 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



 91 

 
PC:  
SN:  
<NN>:  
 



 92 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 300 mg hard capsules 
atazanavir 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 



 93 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON TEXT  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
REYATAZ 50 mg oral powder 
atazanavir 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sachet contains 50 mg of atazanavir (as sulphate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains aspartame and sucrose. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral Powder 
30 sachets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral 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 {MM/YYYY} 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Does not require any special storage conditions.  
 



 94 

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 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/03/267/012 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: REYATAZ 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
<NN>:  



 95 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
REYATAZ 50 mg ORAL POWDER - FOIL SACHET 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
REYATAZ 50 mg oral powder 
Atazanavir 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
3. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg  
 
6. OTHER 
 
 
 
 
  



 96 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 97 

Package leaflet: Information for the user 
 

REYATAZ 100 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 REYATAZ is and what it is used for 
2. What you need to know before you take REYATAZ 
3. How to take REYATAZ 
4. Possible side effects  
5. How to store REYATAZ 
6. Contents of the pack and other information 
 
 
1. What REYATAZ is and What it is used for 
 
REYATAZ 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 REYATAZ reduces the risk of 
developing illnesses linked to HIV infection. 
 
REYATAZ capsules may be used by adults and children 6 years of age and older. Your doctor has 
prescribed REYATAZ 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 REYATAZ 
is best for you. 
 
 
2. What you need to know before you take REYATAZ 
 
Do not take REYATAZ 
 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 REYATAZ 
 if you are taking any of these medicines: see also Other medicines and REYATAZ 

 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) 

 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) 



 98 

 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 REYATAZ 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 
 
REYATAZ 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 REYATAZ. Talk to your doctor or 
pharmacist before taking REYATAZ 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 
 
REYATAZ may affect how well your kidneys work. 
 
Kidney stones have been reported in patients taking REYATAZ. 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 REYATAZ. The signs may be a mild yellowing of the skin or eyes. If you notice any of 
these symptoms please inform your doctor. 
 



 99 

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking 
REYATAZ. 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 REYATAZ 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 REYATAZ 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 REYATAZ 
You must not take REYATAZ with certain medicines. These are listed under Do not take 
REYATAZ, at the start of Section 2.  
 
There are other medicines that may not mix with REYATAZ. Tell your doctor 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 REYATAZ 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 REYATAZ or 2 hours after taking REYATAZ, 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) 
 cyclosporin, 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 REYATAZ. 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). 
 
REYATAZ with food and drink 
It is important that you take REYATAZ 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 for advice before taking this medicine. Atazanavir, the active substance of 
REYATAZ, is excreted in human milk. Patients should not breast-feed while taking REYATAZ. 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 
If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately. 



 100

 
REYATAZ 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 REYATAZ 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor 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 adult dose of REYATAZ capsules is 300 mg once daily with 100 mg ritonavir 
once daily and with food, in combination with other anti-HIV medicines. Your doctor may adjust the 
dose of REYATAZ 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 REYATAZ 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) 

REYATAZ 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. 

 
REYATAZ is also available as an oral powder for use in children at least 3 months old and weighing 
at least 5 kg. Switching to REYATAZ capsules from REYATAZ oral powder is encouraged as soon as 
patients are able to consistently swallow capsules. 
 
A change in dose may occur when switching between oral powder and capsules. Your doctor will 
decide the right dose based on your child’s weight. 
 
There are no dosing recommendations for REYATAZ in paediatric patients less than 3 months of age. 
 
Take REYATAZ capsules with food (a meal or a substantial snack). Swallow the capsules whole. 
Do not open the capsules. 
 
If you take more REYATAZ 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 REYATAZ. 
If you accidentally take more REYATAZ capsules than your doctor recommended, contact your HIV 
doctor at once or contact the nearest hospital for advice. 
 
If you forget to take REYATAZ 
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 REYATAZ 
Do not stop taking REYATAZ before talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 



 101

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 REYATAZ, 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 REYATAZ treatment. Severe rash may be developed 
in association with other symptoms which could be serious. Stop taking REYATAZ 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 start 
REYATAZ 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 REYATAZ. 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. 

 REYATAZ may affect how well your kidneys work. 
 Kidney stones uncommonly happen in people taking REYATAZ. 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 REYATAZ 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) 
 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) 



 102

 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 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 REYATAZ 
 
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. 
Do not store above 25°C. 
 
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 REYATAZ contains 
 
- The active substance is atazanavir. Each capsule contains 100 mg of atazanavir (as sulphate).  
- The other ingredients are crospovidone, lactose monohydrate, and magnesium stearate. The 

capsule shell and printing ink contain gelatine, shellac, ammonium hydroxide, simethicone, 
propylene glycol, indigocarmin (E132) and titanium dioxide (E171). 

 
What REYATAZ looks like and contents of the pack 
 
Each capsule of REYATAZ 100 mg contains 100 mg atazanavir.  
Opaque blue and white capsule printed with white and blue inks, with "BMS 100 mg" on one half and 
with "3623" on the other half. 
 
REYATAZ 100 mg hard capsules are supplied in bottles of 60 capsules.  
 
REYATAZ 100 mg hard capsules are also supplied in blister strips in packs of 60 capsules. 
 
Not all pack sizes may be marketed in all countries.  
 
Marketing Authorisation Holder 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 



 103

Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
Manufacturer 
 
BRISTOL-MYERS SQUIBB S.R.L. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 
 
For any further information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Lietuva 
Bristol-Myers Squibb Kft. 
Tel: + 370 52 369140 
 

България 
Bristol-Myers Squibb Kft. 
Teл.: + 359 800 12 400 
 

Luxembourg/Luxemburg 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 
 

Magyarország 
Bristol-Myers Squibb Kft. 
Tel.: + 36 1 9206 550 
 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Deutschland 
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 
 

Nederland 
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 
 

Eesti 
Bristol-Myers Squibb Kft. 
Tel: + 372 640 1030 
 

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Österreich 
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

France 
Bristol-Myers Squibb SARL 
Tél: + 33 (0) 1 58 83 84 96 
 

Portugal 
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 
 

Hrvatska 
Bristol-Myers Squibb spol. s r.o. 
TEL: + 385 1 2078 508 
 

România 
Bristol-Myers Squibb Kft. 
Tel: + 40 (0)21 272 16 00 
 



 104

Ireland 
Bristol-Myers Squibb Pharmaceuticals uc 
Tel: + 353 (0)1 483 3625 
 

Slovenija 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 386 1 2355 100 

Ísland 
Bristol-Myers Squibb AB hjá Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 
 

Κύπρος 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 
 

Sverige 
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 
 

Latvija 
Bristol-Myers Squibb Kft. 
Tel: + 371 67708347 
 

United Kingdom 
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 
 

This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 



 105

Package leaflet: Information for the user 
 

REYATAZ 150 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 REYATAZ is and what it is used for 
2. What you need to know before you take REYATAZ 
3. How to take REYATAZ 
4. Possible side effects  
5. How to store REYATAZ 
6. Contents of the pack and other information 
 
 
1. What REYATAZ is and What it is used for 
 
REYATAZ 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 REYATAZ reduces the risk of 
developing illnesses linked to HIV infection. 
 
REYATAZ capsules may be used by adults and children 6 years of age and older. Your doctor has 
prescribed REYATAZ 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 REYATAZ 
is best for you. 
 
 
2. What you need to know before you take REYATAZ 
 
Do not take REYATAZ 
 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 REYATAZ 
 if you are taking any of these medicines: see also Other medicines and REYATAZ 

 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) 

 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) 



 106

 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 REYATAZ 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 
 
REYATAZ 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 REYATAZ. Talk to your doctor or 
pharmacist before taking REYATAZ 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 
 
REYATAZ may affect how well your kidneys work. 
 
Kidney stones have been reported in patients taking REYATAZ. 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 REYATAZ. The signs may be a mild yellowing of the skin or eyes. If you notice any of 
these symptoms please inform your doctor. 
 



 107

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking 
REYATAZ. 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 REYATAZ 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 REYATAZ 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 REYATAZ 
You must not take REYATAZ with certain medicines. These are listed under Do not take 
REYATAZ, at the start of Section 2.  
 
There are other medicines that may not mix with REYATAZ. Tell your doctor 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 REYATAZ 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 REYATAZ or 2 hours after taking REYATAZ, 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) 
 cyclosporin, 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 REYATAZ. 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). 
 
REYATAZ with food and drink 
It is important that you take REYATAZ 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 for advice before taking this medicine. Atazanavir, the active substance of 
REYATAZ, is excreted in human milk. Patients should not breast-feed while taking REYATAZ. 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 
If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately. 



 108

 
REYATAZ 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 REYATAZ 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor 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 adult dose of REYATAZ capsules is 300 mg once daily with 100 mg ritonavir 
once daily and with food, in combination with other anti-HIV medicines. Your doctor may adjust the 
dose of REYATAZ 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 REYATAZ 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) 

REYATAZ 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. 

 
REYATAZ is also available as an oral powder for use in children at least 3 months old and weighing 
at least 5 kg. Switching to REYATAZ capsules from REYATAZ oral powder is encouraged as soon as 
patients are able to consistently swallow capsules. 
 
A change in dose may occur when switching between oral powder and capsules. Your doctor will 
decide the right dose based on your child’s weight. 
 
There are no dosing recommendations for REYATAZ in paediatric patients less than 3 months of age. 
 
Take REYATAZ capsules with food (a meal or a substantial snack). Swallow the capsules whole. 
Do not open the capsules. 
 
If you take more REYATAZ 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 REYATAZ. 
If you accidentally take more REYATAZ capsules than your doctor recommended, contact your HIV 
doctor at once or contact the nearest hospital for advice. 
 
If you forget to take REYATAZ 
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 REYATAZ 
Do not stop taking REYATAZ before talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 



 109

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 REYATAZ, 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 REYATAZ treatment. Severe rash may be developed 
in association with other symptoms which could be serious. Stop taking REYATAZ 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 start 
REYATAZ 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 REYATAZ. 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. 

 REYATAZ may affect how well your kidneys work. 
 Kidney stones uncommonly happen in people taking REYATAZ. 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 REYATAZ 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) 
 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) 



 110

 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 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 REYATAZ 
 
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. 
Do not store above 25°C. 
 
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 REYATAZ contains 
 
- The active substance is atazanavir. Each capsule contains 150 mg of atazanavir (as sulphate).  
- The other ingredients are crospovidone, lactose monohydrate, and magnesium stearate. The 

capsule shell and printing ink contain gelatine, shellac, ammonium hydroxide, simethicone, 
propylene glycol, indigocarmin (E132) and titanium dioxide (E171). 

 
What REYATAZ looks like and contents of the pack 
 
Each capsule of REYATAZ 150 mg contains 150 mg atazanavir.  
Opaque blue and powder blue capsule printed with white and blue inks, with "BMS 150 mg" on one 
half and with "3624" on the other half. 
 
REYATAZ 150 mg hard capsules are supplied in bottles of 60 capsules.  
 
REYATAZ 150 mg hard capsules are also supplied in blister strips in packs of 60 capsules. 
 
Not all pack sizes may be marketed in all countries.  
 
Marketing Authorisation Holder 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 



 111

Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
 
Manufacturer 
 
BRISTOL-MYERS SQUIBB S.R.L. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 
 
For any further information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Lietuva 
Bristol-Myers Squibb Kft. 
Tel: + 370 52 369140 
 

България 
Bristol-Myers Squibb Kft. 
Teл.: + 359 800 12 400 
 

Luxembourg/Luxemburg 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 
 

Magyarország 
Bristol-Myers Squibb Kft. 
Tel.: + 36 1 9206 550 
 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Deutschland 
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 
 

Nederland 
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 
 

Eesti 
Bristol-Myers Squibb Kft. 
Tel: + 372 640 1030 
 

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Österreich 
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

France 
Bristol-Myers Squibb SARL 
Tél: + 33 (0) 1 58 83 84 96 
 

Portugal 
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 
 

Hrvatska 
Bristol-Myers Squibb spol. s r.o. 
TEL: + 385 1 2078 508 
 

România 
Bristol-Myers Squibb Kft. 
Tel: + 40 (0)21 272 16 00 
 



 112

Ireland 
Bristol-Myers Squibb Pharmaceuticals uc 
Tel: + 353 (0)1 483 3625 
 

Slovenija 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 386 1 2355 100 
 

Ísland 
Bristol-Myers Squibb AB hjá Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 
 

Κύπρος 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 
 

Sverige 
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 
 

Latvija 
Bristol-Myers Squibb Kft. 
Tel: + 371 67708347 
 

United Kingdom 
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 
 

This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 



 113

Package leaflet: Information for the user 
 

REYATAZ 200 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 REYATAZ is and what it is used for 
2. What you need to know before you take REYATAZ 
3. How to take REYATAZ 
4. Possible side effects  
5. How to store REYATAZ 
6. Contents of the pack and other information 
 
 
1. What REYATAZ is and What it is used for 
 
REYATAZ 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 REYATAZ reduces the risk of 
developing illnesses linked to HIV infection. 
 
REYATAZ capsules may be used by adults and children 6 years of age and older. Your doctor has 
prescribed REYATAZ 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 REYATAZ 
is best for you. 
 
 
2. What you need to know before you take REYATAZ 
 
Do not take REYATAZ 
 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 REYATAZ 
 if you are taking any of these medicines: see also Other medicines and REYATAZ 

 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) 

 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) 



 114

 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 REYATAZ 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 
 
REYATAZ 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 REYATAZ. Talk to your doctor or 
pharmacist before taking REYATAZ 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 
 
REYATAZ may affect how well your kidneys work. 
 
Kidney stones have been reported in patients taking REYATAZ. 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 REYATAZ. The signs may be a mild yellowing of the skin or eyes. If you notice any of 
these symptoms please inform your doctor. 
 



 115

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking 
REYATAZ. 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 REYATAZ 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 REYATAZ 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 REYATAZ 
You must not take REYATAZ with certain medicines. These are listed under Do not take 
REYATAZ, at the start of Section 2.  
 
There are other medicines that may not mix with REYATAZ. Tell your doctor 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 REYATAZ 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 REYATAZ or 2 hours after taking REYATAZ, 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) 
 cyclosporin, 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 REYATAZ. 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). 
 
REYATAZ with food and drink 
It is important that you take REYATAZ 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 for advice before taking this medicine. Atazanavir, the active substance of 
REYATAZ, is excreted in human milk. Patients should not breast-feed while taking REYATAZ. 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 
If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately. 



 116

 
REYATAZ 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 REYATAZ 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor 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 adult dose of REYATAZ capsules is 300 mg once daily with 100 mg ritonavir 
once daily and with food, in combination with other anti-HIV medicines. Your doctor may adjust the 
dose of REYATAZ 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 REYATAZ 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) 

REYATAZ 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. 

 
REYATAZ is also available as an oral powder for use in children at least 3 months old and weighing 
at least 5 kg. Switching to REYATAZ capsules from REYATAZ oral powder is encouraged as soon as 
patients are able to consistently swallow capsules. 
 
A change in dose may occur when switching between oral powder and capsules. Your doctor will 
decide the right dose based on your child’s weight. 
 
There are no dosing recommendations for REYATAZ in paediatric patients less than 3 months of age. 
 
Take REYATAZ capsules with food (a meal or a substantial snack). Swallow the capsules whole. 
Do not open the capsules. 
 
If you take more REYATAZ 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 REYATAZ. 
If you accidentally take more REYATAZ capsules than your doctor recommended, contact your HIV 
doctor at once or contact the nearest hospital for advice. 
 
If you forget to take REYATAZ 
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 REYATAZ 
Do not stop taking REYATAZ before talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 



 117

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 REYATAZ, 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 REYATAZ treatment. Severe rash may be developed 
in association with other symptoms which could be serious. Stop taking REYATAZ 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 start 
REYATAZ 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 REYATAZ. 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. 

 REYATAZ may affect how well your kidneys work. 
 Kidney stones uncommonly happen in people taking REYATAZ. 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 REYATAZ 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) 
 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) 



 118

 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 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 REYATAZ 
 
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. 
Do not store above 25°C. 
 
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 REYATAZ contains 
 
- The active substance is atazanavir. Each capsule contains 200 mg of atazanavir (as sulphate).  
- The other ingredients are crospovidone, lactose monohydrate, and magnesium stearate. The 

capsule shell and printing ink contain gelatine, shellac, ammonium hydroxide, simethicone, 
propylene glycol, indigocarmin (E132) and titanium dioxide (E171). 

 
What REYATAZ looks like and contents of the pack 
 
Each capsule of REYATAZ 200 mg contains 200 mg atazanavir.  
Opaque blue capsule printed with white ink, with "BMS 200 mg" on one half and with "3631" on the 
other half. 
 
REYATAZ 200 mg hard capsules are supplied in bottles of 60 capsules. Either one or three bottles of 
60 hard capsules are provided in one carton. 
 
REYATAZ 200 mg hard capsules are also supplied in blister strips in packs of 60 capsules. 
 
Not all pack sizes may be marketed in all countries.  
 



 119

Marketing Authorisation Holder 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
Manufacturer 
 
BRISTOL-MYERS SQUIBB S.R.L. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 
 
For any further information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Lietuva 
Bristol-Myers Squibb Kft. 
Tel: + 370 52 369140 
 

България 
Bristol-Myers Squibb Kft. 
Teл.: + 359 800 12 400 
 

Luxembourg/Luxemburg 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 
 

Magyarország 
Bristol-Myers Squibb Kft. 
Tel.: + 36 1 9206 550 
 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Deutschland 
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 
 

Nederland 
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 
 

Eesti 
Bristol-Myers Squibb Kft. 
Tel: + 372 640 1030 
 

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Österreich 
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

France 
Bristol-Myers Squibb SARL 
Tél: + 33 (0) 1 58 83 84 96 
 

Portugal 
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 
 



 120

Hrvatska 
Bristol-Myers Squibb spol. s r.o. 
TEL: + 385 1 2078 508 
 

România 
Bristol-Myers Squibb Kft. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
Bristol-Myers Squibb Pharmaceuticals uc 
Tel: + 353 (0)1 483 3625 
 

Slovenija 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 386 1 2355 100 
 

Ísland 
Bristol-Myers Squibb AB hjá Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 
 

Κύπρος 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 
 

Sverige 
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 
 

Latvija  
Bristol-Myers Squibb Kft. 
Tel: + 371 67708347 
 

United Kingdom 
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 
 

This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 



 121

Package leaflet: Information for the user 
 

REYATAZ 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 REYATAZ is and what it is used for 
2. What you need to know before you take REYATAZ 
3. How to take REYATAZ 
4. Possible side effects  
5. How to store REYATAZ 
6. Contents of the pack and other information 
 
 
1. What REYATAZ is and What it is used for 
 
REYATAZ 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 REYATAZ reduces the risk of 
developing illnesses linked to HIV infection. 
 
REYATAZ capsules may be used by adults and children 6 years of age and older. Your doctor has 
prescribed REYATAZ 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 REYATAZ 
is best for you. 
 
 
2. What you need to know before you take REYATAZ 
 
Do not take REYATAZ 
 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 REYATAZ 
 if you are taking any of these medicines: see also Other medicines and REYATAZ 

 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) 

 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) 



 122

 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 REYATAZ 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 
 
REYATAZ 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 REYATAZ. Talk to your doctor or 
pharmacist before taking REYATAZ 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 
 
REYATAZ may affect how well your kidneys work. 
 
Kidney stones have been reported in patients taking REYATAZ. 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 REYATAZ. The signs may be a mild yellowing of the skin or eyes. If you notice any of 
these symptoms please inform your doctor. 
 



 123

Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking 
REYATAZ. 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 REYATAZ 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 REYATAZ 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 REYATAZ 
You must not take REYATAZ with certain medicines. These are listed under Do not take 
REYATAZ, at the start of Section 2.  
 
There are other medicines that may not mix with REYATAZ. Tell your doctor 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 REYATAZ to prevent pregancy, 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 REYATAZ or 2 hours after taking REYATAZ, 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) 
 cyclosporin, 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 REYATAZ. 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). 
 
REYATAZ with food and drink 
It is important that you take REYATAZ 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 for advice before taking this medicine. Atazanavir, the active substance of 
REYATAZ, is excreted in human milk. Patients should not breast-feed while taking REYATAZ. 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 
If you feel dizzy or lightheaded, do not drive or use machines and contact your doctor immediately. 



 124

 
REYATAZ 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 REYATAZ 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor 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 adult dose of REYATAZ capsules is 300 mg once daily with 100 mg ritonavir 
once daily and with food, in combination with other anti-HIV medicines. Your doctor may adjust the 
dose of REYATAZ 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 REYATAZ 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) 

REYATAZ 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. 

 
REYATAZ is also available as an oral powder for use in children at least 3 months old and weighing 
at least 5 kg. Switching to REYATAZ capsules from REYATAZ oral powder is encouraged as soon as 
patients are able to consistently swallow capsules. 
 
A change in dose may occur when switching between oral powder and capsules. Your doctor will 
decide the right dose based on your child’s weight. 
 
There are no dosing recommendations for REYATAZ in paediatric patients less than 3 months of age. 
 
Take REYATAZ capsules with food (a meal or a substantial snack). Swallow the capsules whole. 
Do not open the capsules. 
 
If you take more REYATAZ 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 REYATAZ. 
If you accidentally take more REYATAZ capsules than your doctor recommended, contact your HIV 
doctor at once or contact the nearest hospital for advice. 
 
If you forget to take REYATAZ 
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 REYATAZ 
Do not stop taking REYATAZ before talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 



 125

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 REYATAZ, 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 REYATAZ treatment. Severe rash may be developed 
in association with other symptoms which could be serious. Stop taking REYATAZ 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 start 
REYATAZ 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 REYATAZ. 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. 

 REYATAZ may affect how well your kidneys work. 
 Kidney stones uncommonly happen in people taking REYATAZ. 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 REYATAZ 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) 
 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) 



 126

 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 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 REYATAZ 
 
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. 
Do not store above 25°C. 
 
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 REYATAZ contains 
 
- The active substance is atazanavir. Each capsule contains 300 mg of atazanavir (as sulphate).  
- The other ingredients are crospovidone, lactose monohydrate, and magnesium stearate. The 

capsule shell and printing ink contain gelatine, shellac, ammonium hydroxide, simethicone, red 
iron oxide, black iron oxide, yellow iron oxide, propylene glycol, indigocarmin (E132) and 
titanium dioxide (E171). 

 
What REYATAZ looks like and contents of the pack 
 
Each capsule of REYATAZ 300 mg contains 300 mg atazanavir.  
Opaque red and blue capsule printed with white ink, with "BMS 300 mg" on one half and with "3622" 
on the other half. 
 
REYATAZ 300 mg hard capsules are supplied in bottles of 30 capsules. Either one or three bottles of 
30 hard capsules are provided in one carton. 
 
REYATAZ 300 mg hard capsules are also supplied in blister strips in packs of 30 capsules. 
 
Not all pack sizes may be marketed in all countries.  
 



 127

Marketing Authorisation Holder 
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
Manufacturer 
 
BRISTOL-MYERS SQUIBB S.R.L. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 
 
For any further information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Lietuva 
Bristol-Myers Squibb Kft. 
Tel: + 370 52 369140 
 

България 
Bristol-Myers Squibb Kft. 
Teл.: + 359 800 12 400 
 

Luxembourg/Luxemburg 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 
 

Magyarország 
Bristol-Myers Squibb Kft. 
Tel.: + 36 1 9206 550 
 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Deutschland 
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 
 

Nederland 
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 
 

Eesti 
Bristol-Myers Squibb Kft. 
Tel: + 372 640 1030 
 

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Österreich 
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

France 
Bristol-Myers Squibb SARL 
Tél: + 33 (0) 1 58 83 84 96 
 

Portugal 
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 
 



 128

Hrvatska 
Bristol-Myers Squibb spol. s r.o. 
TEL: + 385 1 2078 508 
 

România 
Bristol-Myers Squibb Kft. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
Bristol-Myers Squibb Pharmaceuticals uc 
Tel: + 353 (0)1 483 3625 
 

Slovenija 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 386 1 2355 100 
 

Ísland 
Bristol-Myers Squibb AB hjá Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 
 

Κύπρος 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 
 

Sverige 
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 
 

Latvija 
Bristol-Myers Squibb Kft. 
Tel: + 371 67708347 
 

United Kingdom 
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 
 

This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 



 129

Package leaflet: Information for the user 
 

REYATAZ 50 mg oral powder 
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 REYATAZ is and what it is used for 
2. What you need to know before you take REYATAZ 
3. How to take REYATAZ 
4. Possible side effects  
5. How to store REYATAZ 
6. Contents of the pack and other information 
 
 
1. What REYATAZ is and What it is used for 
 
REYATAZ 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 REYATAZ reduces the risk of 
developing illnesses linked to HIV infection. 
 
REYATAZ oral powder may be used by children at least 3 months of age and weighing at least 5 kg 
(see section 3 How to take REYATAZ). Your doctor has prescribed REYATAZ for you because you 
are infected by the HIV that causes Acquired Immunodeficiency Syndrome (AIDS). It should always 
be used with a low dose of ritonavir and in combination with other anti-HIV medicines. Your doctor 
will discuss with you which combination of these medicines with REYATAZ is best for you. 
 
 
2. What you need to know before you take REYATAZ 
 
Do not take REYATAZ 
 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 REYATAZ 
 if you are taking any of these medicines: see also Other medicines and REYATAZ 

 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) 

 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) 



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 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 REYATAZ 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 
 
REYATAZ 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 REYATAZ. Talk to your doctor or 
pharmacist before taking REYATAZ 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 
 
REYATAZ may affect how well your kidneys work. 
 
Kidney stones have been reported in patients taking REYATAZ. 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 REYATAZ. The signs may be a mild yellowing of the skin or eyes. If you notice any of 
these symptoms please inform your doctor. 
 



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Serious skin rash, including Stevens-Johnson syndrome, has been reported in patients taking 
REYATAZ. 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 REYATAZ 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 REYATAZ 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 REYATAZ 
You must not take REYATAZ with certain medicines. These are listed under Do not take 
REYATAZ, at the start of Section 2.  
 
There are other medicines that may not mix with REYATAZ. Tell your doctor 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 REYATAZ to prevent pregancy, 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 REYATAZ or 2 hours after taking REYATAZ, 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) 
 cyclosporin, 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 REYATAZ. 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). 
 
REYATAZ with food and drink 
See section 3 How to take REYATAZ. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. Atazanavir, the active substance of REYATAZ, is 
excreted in human milk. Patients should not breast-feed while taking REYATAZ. 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 
If you feel dizzy or lightheaded, do not drive or use machines, and contact your doctor immediately. 
 



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REYATAZ oral powder contains : 
 63 mg of aspartame per sachet. Aspartame is a source of phenylalanine. It may be harmful if you 

have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because 
the body cannot remove it properly. 

 1.3 g of sucrose per sachet. If you have been told by your doctor that your child has an intolerance 
to some sugars, contact your doctor before giving this medicinal product to your child. 

 
 
3. How to take REYATAZ 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor 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.  
 
For children (at least 3 months of age and weighing at least 5 kg), your child's doctor will decide 
the right dose based on your child's weight. The dose of REYATAZ oral powder for children is 
calculated by body weight and is taken once daily with food and ritonavir as shown below: 

Body Weight 
(kg) 

REYATAZ Dose once daily 
(mg) 

Ritonavir Dose once daily 
(mg) 

At least 5 to less than 15 200 mg (4 sachetsa) 80 mgb 
At least 15 to less than 35 250 mg (5 sachetsa) 80 mgb 

at least 35 300 mg (6 sachetsa) 100 mgc 
aEach sachet contains 50 mg of REYATAZ 
bRitonavir oral solution 
cRitonavir oral solution or capsule/tablet 

 
REYATAZ is also available in capsules for use in adults and children at least 6 years of age who 
weigh at least 15 kg and who are able to swallow the capsules. Switching from REYATAZ oral 
powder to REYATAZ capsules is encouraged as soon as patients are able to consistently swallow 
capsules. 
 
A change in dose may occur when switching between oral powder and capsules. Your doctor will 
decide the right dose based on your child’s weight. 
 
There are no dosing recommendations for REYATAZ in paediatric patients less than 3 months of age. 
 
Instructions for REYATAZ oral powder:  
 For children who are able to drink from a cup, REYATAZ oral powder must be taken with food 

or drinks. If REYATAZ oral powder is mixed with water, food should also be taken at the same 
time. 

 For children who cannot eat solid food or drink from a cup, REYATAZ oral powder must be 
mixed with infant formula and should be given using an oral syringe. Ask your pharmacist for an 
oral syringe. Do not use an infant bottle to give REYATAZ mixed with infant formula.  

 See the "Instructions for use" at the end of the package leaflet for how to prepare and give a dose 
of REYATAZ oral powder. 

 REYATAZ oral powder should be given within 60 minutes of mixing. 
 
If you take more REYATAZ 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 REYATAZ. 
If you accidentally take or give more REYATAZ oral powder than your doctor recommended, contact 
your HIV doctor at once or contact the nearest hospital for advice. 
 
If you forget to take REYATAZ 
If you miss a dose or if you forget to give your child a dose, take or give the missed dose as soon as 
possible with food and then take or give the next scheduled dose at its regular time. If it is almost time 



 133

for your or your child's next dose, do not take or give the missed dose. Wait and take or give the next 
dose at its regular time. Do not take or give a double dose to make up for a forgotten dose.  
 
If you stop taking REYATAZ 
Do not stop taking REYATAZ before talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
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 REYATAZ, 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 REYATAZ treatment. Severe rash may be developed 
in association with other symptoms which could be serious. Stop taking REYATAZ 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 start 
REYATAZ 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 REYATAZ. 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. 

 REYATAZ may affect how well your kidneys work. 
 Kidney stones uncommonly happen in people taking REYATAZ. 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 REYATAZ 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) 



 134

 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) 
 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 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 REYATAZ 
 
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 carton or sachet. The expiry date 
refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. Do not open the sachet until 
ready to use. 
 
After mixing the oral powder with food or drinks, it may be stored at room temperature (not above 
30oC) for up to 1 hour. 
 
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 REYATAZ contains 
 
- The active substance is atazanavir. Each sachet contains 50 mg of atazanavir (as sulphate).  
- The other ingredients are aspartame (E951), sucrose and orange vanilla flavour. 
 
What REYATAZ looks like and contents of the pack 
 



 135

Each sachet of REYATAZ 50 mg oral powder contains 50 mg atazanavir.  
 
One pack size is available: 1 carton with 30 sachets. 
 
 
Marketing Authorisation Holder  
 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland  
 
Manufacturer 
 
Swords Laboratories T/A Lawrence Laboratories, 
Unit 12, The Distribution Centre, Shannon Industrial Estate, 
Shannon, Co. Clare,  
Ireland 
 
For any further information about this medicine, please contact the local representative of the 
Marketing Authorisation Holder: 
 
Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Lietuva 
Bristol-Myers Squibb Kft. 
Tel: + 370 52 369140 
 

България 
Bristol-Myers Squibb Kft. 
Teл.: + 359 800 12 400 
 

Luxembourg/Luxemburg 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 
 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 
 

Magyarország 
Bristol-Myers Squibb Kft. 
Tel.: + 36 1 9206 550 
 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Deutschland 
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 
 

Nederland 
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 
 

Eesti 
Bristol-Myers Squibb Kft. 
Tel: + 372 640 1030 
 

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Österreich 
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 



 136

France 
Bristol-Myers Squibb SARL 
Tél: + 33 (0)1 58 83 84 96 

Portugal 
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 
 

Hrvatska 
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 
 

România 
Bristol-Myers Squibb Kft. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
Bristol-Myers Squibb Pharmaceuticals uc 
Tel: + 353 (0)1 483 3625 
 

Slovenija 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 386 1 2355 100 
 

Ísland 
Bristol-Myers Squibb AB hjá Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 
 

Κύπρος 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 
 

Sverige 
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 
 

Latvija 
Bristol-Myers Squibb Kft. 
Tel: + 371 67708347 
 

United Kingdom 
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 
 

This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 



 137

Instructions for use 
 
These instructions show you how to prepare and give a dose of REYATAZ oral powder. Make sure 
that you read and understand these instructions before giving this medicine to your child. 
Your child's doctor will decide the right dose based on your child's age and weight.  
 
Always give your child the medicine within 60 minutes of mixing. 
 
Before giving the medicine 

1. Determine the dose and the number of REYATAZ oral powder sachets needed (see section 3 
How to take REYATAZ). 

2. Before use, tap the sachet. Cut each sachet along the dotted line. 
3. Choose the appropriate option listed below for giving REYATAZ oral powder to your child. 

Larger volumes or quantities of liquid infant formula, beverage or food may be used. Ensure 
that all the infant formula, beverage or food that contains the medicine is taken. 

Preparing and giving the medicine with liquid infant formula using a medicine cup or small 
container and oral syringe (ask your pharmacist for an oral syringe): 

1. Take a medicine cup or small container and put the sachets’ content in the cup or small 
container. 

2. Add 10 ml of prepared liquid infant formula and mix using a spoon. 
3. Put the oral syringe tip into the mixture and pull back the plunger until the full amount of 

infant formula is taken up. 
4. Place the syringe in your child's mouth towards the cheek and push the plunger down to 

release the medicine. 
5. Put another 10 ml of prepared infant formula in the cup or container and rinse the remaining 

oral powder from the cup or container.  
6. Put the syringe tip into the mixture and pull back the plunger until the full amount of infant 

formula is taken up. 
7. Place the syringe in your child's mouth towards the cheek and push the plunger down to 

release the medicine. 
8. Give to your child the recommended dose of ritonavir immediately after giving REYATAZ 

oral powder. 

Preparing and giving the medicine with drinks 

1. Put the sachets’ content in a small drinking cup. 
2. Add 30 ml of the drink and mix with a spoon.  
3. Have the child drink the mixture. 
4. Add another 15 ml of the drink, mix and have the child drink the mixture. 
5. If water is used, food should also be taken at the same time. 

Preparing and giving the medicine with food 

1. Fill a small container with the sachets' content.  
2. Add a minimum of one tablespoon of food and mix. 
3. Feed your child with the mixture. 
4. Add an additional tablespoon in the container, mix and feed to your child again. 

 
If you have any questions on how to prepare or give a dose of REYATAZ oral powder, talk to your 
doctor, pharmacist or nurse.  
 
 


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