Darunavir Mylan

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 75 mg film-coated tablets 

Darunavir Mylan 150 mg film-coated tablets 

Darunavir Mylan 300 mg film-coated tablets 

Darunavir Mylan 600 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION  

 

Darunavir Mylan 75 mg film-coated tablets 

Each film-coated tablet contains 75 mg of darunavir. 

 

Darunavir Mylan 150 mg film-coated tablets 

Each film-coated tablet contains 150 mg of darunavir. 

 

Darunavir Mylan 300 mg film-coated tablets 

Each film-coated tablet contains 300 mg of darunavir. 

 

Darunavir Mylan 600 mg film-coated tablets 

Each film-coated tablet contains 600 mg of darunavir. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Darunavir Mylan 75 mg film-coated tablets 

Film-coated tablet. 

White to off-white, oval shaped, biconvex film-coated tablets approximately 9.7 mm by 4.6 mm, 

debossed with ‘M’ on one side and ‘DV1' on the other side. 

 

Darunavir Mylan 150 mg film-coated tablets 

Film-coated tablet. 

White to off-white, capsule shaped, biconvex film-coated tablets approximately 12.75 mm by 6.3 mm 

debossed with ‘M’ on one side and ‘DV2’ on the other side. 

 

Darunavir Mylan 300 mg film-coated tablets 

Film-coated tablet. 

White to off-white, oval shaped, biconvex film coated tablets approximately 16.5 mm by 8.2 mm, 

debossed with 'M' on one side of the tablet and 'DV3' on other side. 

 

Darunavir Mylan 600 mg film-coated tablets 

Film-coated tablet.  

White to off-white, oval shaped, biconvex film-coated tablets approximately 21.2 mm by 10.6 mm, 

debossed with ‘M’ on one side and ‘DV5’ on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Darunavir, co-administered with low dose ritonavir is indicated in combination with other 

antiretroviral medicinal products for the treatment of patients with human immunodeficiency virus 

(HIV-1) infection (see section 4.2). 

 



3 

 

Darunavir Mylan 75 mg, 150 mg, 300 mg and 600 mg tablets may be used to provide suitable dose 

regimens (see section 4.2): 

● For the treatment of HIV-1 infection in antiretroviral treatment (ART)-experienced adult 

patients, including those that have been highly pre-treated. 

● For the treatment of HIV-1 infection in paediatric patients from the age of 3 years and at least 

15 kg body weight. 

 

In deciding to initiate treatment with darunavir co-administered with low dose ritonavir, careful 

consideration should be given to the treatment history of the individual patient and the patterns of 

mutations associated with different agents. Genotypic or phenotypic testing (when available) and 

treatment history should guide the use of darunavir (see sections 4.2, 4.4 and 5.1). 

 

4.2 Posology and method of administration 

 

Therapy should be initiated by a health care provider experienced in the management of HIV 

infection. After therapy with darunavir has been initiated, patients should be advised not to alter the 

dosage, dose form or discontinue therapy without discussing with their health care provider. 

 

Posology 

 

Darunavir Mylan must always be given orally with low dose ritonavir as a pharmacokinetic enhancer 

and in combination with other antiretroviral medicinal products. The Summary of Product 

Characteristics of ritonavir must, therefore, be consulted prior to initiation of therapy with darunavir. 

 

ART-experienced adult patients 

The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken 

with food. Darunavir Mylan 75 mg, 150 mg, 300 mg and 600 mg tablets can be used to construct the 

twice daily 600 mg regimen. 

 

The use of 75 mg and 150 mg tablets to achieve the recommended dose is appropriate when there is 

a difficulty in swallowing the 300 mg or 600 mg tablets. Before prescribing darunavir tablets, young 

children should be assessed for the ability to swallow intact tablets. For young children unable to 

swallow tablets, more suitable formulations containing darunavir should be checked for their 

availability. 

 

ART-naïve adult patients 

For dosage recommendations in ART-naïve patients see the Summary of Product Characteristics for 

darunavir 400 mg and 800 mg tablets. 

 

ART-naïve paediatric patients (3 to 17 years of age and weighing at least 15 kg) 

The weight-based dose of darunavir and ritonavir in paediatric patients is provided in the table below. 

 

Recommended dose for treatment-naïve paediatric patients (3 to 17 years) with darunavir 

tablets and ritonavira 

Body weight (kg) Dose (once daily with food) 

≥ 15 kg to < 30 kg 600 mg darunavir/100 mg ritonavir once daily 

≥ 30 kg to < 40 kg 675 mg darunavir/100 mg ritonavir once daily 

≥ 40 kg 800 mg darunavir/100 mg ritonavir once daily 
a ritonavir oral solution: 80 mg/ml 

 

ART-experienced paediatric patients (3 to 17 years of age and weighing at least 15 kg) 

Darunavir twice daily taken with ritonavir taken with food is usually recommended. 

 

A once daily dose regimen of darunavir taken with ritonavir taken with food may be used in patients 

with prior exposure to antiretroviral medicinal products but without darunavir resistance associated 



4 

 

mutations (DRV-RAMs)* and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell 

count ≥ 100 cells x 106/l. 

*   DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V 

 

The weight-based dose of darunavir and ritonavir in paediatric patients is provided in the table below. 

The recommended dose of darunavir with low dose ritonavir should not exceed the recommended adult 

dose (600/100 mg twice daily or 800/100 mg once daily). 

 

Recommended dose for treatment-experienced paediatric patients 

(3 to 17 years) with darunavir tablets and ritonavira 

Body weight (kg) Dose (once daily with food) Dose (twice daily with food) 

≥ 15 kg–< 30 kg 600 mg darunavir/100 mg ritonavir 

once daily 

375 mg darunavir/50 mg ritonavir 

twice daily 

≥ 30 kg–< 40 kg 675 mg darunavir/100 mg ritonavir 

once daily 

450 mg darunavir/60 mg ritonavir 

twice daily 

≥ 40 kg 800 mg darunavir/100 mg ritonavir 

once daily 

600 mg darunavir/100 mg ritonavir 

twice daily 
a ritonavir oral solution: 80 mg/ml 

 

For ART-experienced paediatric patients HIV genotypic testing is recommended. However, when 

HIV genotypic testing is not feasible, the darunavir/ritonavir once daily dosing regimen is 

recommended in HIV protease inhibitor-naïve paediatric patients and the twice daily dosing regimen 

is recommended in HIV protease inhibitor-experienced patients. 

 

Advice on missed doses 

In case a dose of darunavir and/or ritonavir is missed within 6 hours of the time it is usually taken, 

patients should be instructed to take the prescribed dose of darunavir and ritonavir with food as soon 

as possible. If this is noticed later than 6 hours after the time it is usually taken, the missed dose 

should not be taken and the patient should resume the usual dosing schedule. 

 

This guidance is based on the 15 hour half-life of darunavir in the presence of ritonavir and the 

recommended dosing interval of approximately 12 hours. 

 

Special populations 

 

Elderly 

Limited information is available in this population, and therefore, darunavir should be used with 

caution in this age group (see sections 4.4 and 5.2). 

 

Hepatic impairment 

Darunavir is metabolised by the hepatic system. No dose adjustment is recommended in patients with 

mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, however, darunavir 

should be used with caution in these patients. No pharmacokinetic data are available in patients with 

severe hepatic impairment. Severe hepatic impairment could result in an increase of darunavir 

exposure and a worsening of its safety profile. Therefore, darunavir must not be used in patients with 

severe hepatic impairment (Child-Pugh Class C) (see sections 4.3, 4.4 and 5.2). 

 

Renal impairment 

No dose adjustment is required in patients with renal impairment (see sections 4.4 and 5.2). 

 

Paediatric population 

Darunavir/ritonavir should not be used in children with a body weight of less than 15 kg as the dose 

for this population has not been established in a sufficient number of patients (see section 5.1). 

Darunavir/ritonavir should not be used in children below 3 years of age because of safety concerns 

(see sections 4.4 and 5.3). 

 



5 

 

The weight-based dose regimen for darunavir and ritonavir is provided in the tables above.  

 

Pregnancy and postpartum 

No dose adjustment is required for darunavir/ritonavir during pregnancy and postpartum. 

Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential 

risk (see sections 4.4, 4.6 and 5.2). 

 

Method of administration 

 

Patients should be instructed to take Darunavir Mylan with low dose ritonavir within 30 minutes after 

completion of a meal. The type of food does not affect the exposure to darunavir (see sections 4.4, 4.5 

and 5.2). 

 

4.3 Contraindications 

 

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

 

Patients with severe (Child-Pugh Class C) hepatic impairment. 

 

Combination of rifampicin with darunavir with concomitant low dose ritonavir (see section 4.5). 

 

Co-administration with the combination product lopinavir/ritonavir (see section 4.5). 

 

Co-administration with herbal preparations containing St John’s wort (Hypericum perforatum) (see 

section 4.5). 

 

Co-administration of darunavir with low dose ritonavir, with active substances that are highly 

dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with 

serious and/or life-threatening events. These active substances include e.g.: 

- alfuzosin  
- amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine 
- astemizole, terfenadine  
- colchicine when used in patients with renal and/or hepatic impairment (see section 4.5) 
- ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine) 
- elbasvir/grazoprevir 
- cisapride 
- dapoxetine 
- domperidone 
- naloxegol 
- lurasidone, pimozide, quetiapine, sertindole (see section 4.5) 
- triazolam, midazolam administered orally (for caution on parenterally administered midazolam, 

see section 4.5) 

- sildenafil - when used for the treatment of pulmonary arterial hypertension, avanafil  
- simvastatin, lovastatin and lomitapide (see section 4.5) 
- dabigatran, ticagrelor (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. 

 

Regular assessment of virological response is advised. In the setting of lack or loss of virological 

response, resistance testing should be performed. 

 

Darunavir must always be given orally with low dose ritonavir as a pharmacokinetic enhancer and in 

combination with other antiretroviral medicinal products (see section 5.2). The Summary of Product 



6 

 

Characteristics of ritonavir as appropriate, must therefore be consulted prior to initiation of therapy 

with darunavir.  

 

Increasing the dose of ritonavir from that recommended in section 4.2 did not significantly affect 

darunavir concentrations. It is not recommended to alter the dose of ritonavir. 

 

Darunavir binds predominantly to α1-acid glycoprotein. This protein binding is concentration-

dependent indicative for saturation of binding. Therefore, protein displacement of medicinal products 

highly bound to α1-acid glycoprotein cannot be ruled out (see section 4.5). 

 

ART-experienced patients - once daily dosing 

 

Darunavir used in combination with cobicistat or low dose ritonavir once daily in ART-experienced 

patients should not be used in patients with one or more darunavir resistance associated mutations 

(DRV-RAMs) or HIV-1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 106/l (see section 

4.2). Combinations with optimised background regimen (OBRs) other than ≥ 2 NRTIs have not been 

studied in this population. Limited data are available in patients with HIV-1 clades other than B (see 

section 5.1). 

 

Paediatric population 

 

Darunavir is not recommended for use in paediatric patients below 3 years of age or less than 15 kg 

body weight (see sections 4.2 and 5.3). 

 

Pregnancy 

 

Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential 

risk. Caution should be used in pregnant women with concomitant medications which may further 

decrease darunavir exposure (see sections 4.5 and 5.2). 

 

Elderly 

 

As limited information is available on the use of darunavir in patients aged 65 and over, caution should 

be exercised in the administration of darunavir in elderly patients, reflecting the greater frequency of 

decreased hepatic function and of concomitant disease or other therapy (see sections 4.2 and 5.2).  

 

Severe skin reactions 

 

During the darunavir/ritonavir clinical development program (N=3,063), severe skin reactions, which 

may be accompanied with fever and/or elevations of transaminases, have been reported in 0.4% of 

patients. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) and Stevens-Johnson 

syndrome has been rarely (< 0.1%) reported, and during post-marketing experience toxic epidermal 

necrolysis and acute generalised exanthematous pustulosis have been reported. Darunavir should be 

discontinued immediately if signs or symptoms of severe skin reactions develop. These can include, 

but are not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or 

joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia. 

 

Rash occurred more commonly in treatment-experienced patients receiving regimens containing 

darunavir/ritonavir + raltegravir compared to patients receiving darunavir/ritonavir without raltegravir 

or raltegravir without darunavir (see section 4.8). 

 

Darunavir contains a sulphonamide moiety. Darunavir Mylan should be used with caution in patients 

with a known sulphonamide allergy. 

 

Hepatotoxicity 

 



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Drug-induced hepatitis (e.g. acute hepatitis, cytolytic hepatitis) has been reported with darunavir. 

During the darunavir/ritonavir clinical development program (N=3,063), hepatitis was reported in 

0.5% of patients receiving combination antiretroviral therapy with darunavir/ritonavir. Patients with 

pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for 

liver function abnormalities including severe and potentially fatal hepatic adverse reactions. In case of 

concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for 

these medicinal products. 

 

Appropriate laboratory testing should be conducted prior to initiating therapy with darunavir/ritonavir 

and patients should be monitored during treatment. Increased AST/ALT monitoring should be 

considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-

treatment elevations of transaminases, especially during the first several months of 

darunavir/ritonavir treatment. 

 

If there is evidence of new or worsening liver dysfunction (including clinically significant elevation 

of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver 

tenderness, hepatomegaly) in patients using darunavir/ritonavir, interruption or discontinuation of 

treatment should be considered promptly. 

 

Patients with coexisting conditions  

 

Hepatic impairment 

The safety and efficacy of darunavir have not been established in patients with severe underlying 

liver disorders and darunavir is therefore contraindicated in patients with severe hepatic impairment. 

Due to an increase in the unbound darunavir plasma concentrations, darunavir should be used with 

caution in patients with mild or moderate hepatic impairment (see sections 4.2, 4.3 and 5.2). 

 

Renal impairment 

No special precautions or dose adjustments for darunavir/ritonavir are required in patients with renal 

impairment. As darunavir and ritonavir are highly bound to plasma proteins, it is unlikely that they 

will be significantly removed by haemodialysis or peritoneal dialysis. Therefore, no special 

precautions or dose adjustments are required in these patients (see sections 4.2 and 5.2). 

 

Haemophiliac patients 

There have been reports of increased bleeding, including spontaneous skin haematomas and 

haemarthrosis in patients with haemophilia type A and B treated with PIs. In some patients additional 

factor VIII was given. In more than half of the reported cases, treatment with PIs 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 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. 

 

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. 

 

Immune reconstitution inflammatory syndrome 



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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 

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

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

examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and 

pneumonia caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii). Any 

inflammatory symptoms should be evaluated and treatment instituted when necessary. In addition, 

reactivation of herpes simplex and herpes zoster has been observed in clinical studies with darunavir 

co-administered with low dose ritonavir. 

 

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

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

these events can occur many months after initiation of treatment (see section 4.8). 

 

Interactions with medicinal products 

 

Several of the interaction studies have been performed with darunavir at lower than recommended 

doses. The effects on co-administered medicinal products may thus be underestimated and clinical 

monitoring of safety may be indicated. For full information on interactions with other medicinal 

products see section 4.5. 

 

Efavirenz in combination with boosted darunavir once daily may result in sub-optimal darunavir Cmin. 

If efavirenz is to be used in combination with darunavir, the darunavir/ritonavir 600/100 mg twice 

daily regimen should be used (see section 4.5). 

 

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and 

strong inhibitors of CYP3A and P-glycoprotein (P-gp; see sections 4.3 and 4.5). 

 

Darunavir Mylan contains sodium 

 

Darunavir Mylan 75 mg, 150 mg, 300 mg and 600 mg film-coated tablets contain less than 1 mmol 

sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Interaction studies have only been performed in adults. 

 

Medicinal products that may be affected by darunavir boosted with ritonavir 

Darunavir and ritonavir are inhibitors of CYP3A, CYP2D6 and P-gp. Co-administration of darunavir/ 

ritonavir with medicinal products primarily metabolised by CYP3A and/or CYP2D6 or transported by 

P-gp may result in increased systemic exposure to such medicinal products, which could increase or 

prolong their therapeutic effect and adverse reactions. 

 

Darunavir co-administered with low dose ritonavir must not be combined with medicinal products that 

are highly dependent on CYP3A for clearance and for which increased systemic exposure is associated 

with serious and/or life-threatening events (narrow therapeutic index) (see section 4.3). 

 

The overall pharmacokinetic enhancement effect by ritonavir was an approximate 14-fold increase in 

the systemic exposure of darunavir when a single dose of 600 mg darunavir was given orally in 

combination with ritonavir at 100 mg twice daily. Therefore, darunavir must only be used in 

combination with low dose ritonavir as a pharmacokinetic enhancer (see sections 4.4 and 5.2). 

 

A clinical study utilising a cocktail of medicinal products that are metabolised by cytochromes 

CYP2C9, CYP2C19 and CYP2D6 demonstrated an increase in CYP2C9 and CYP2C19 activity and 

inhibition of CYP2D6 activity in the presence of darunavir/ritonavir, which may be attributed to the 

presence of low dose ritonavir. Co-administration of darunavir and ritonavir with medicinal products 



9 

 

which are primarily metabolised by CYP2D6 (such as flecainide, propafenone, metoprolol) may result 

in increased plasma concentrations of these medicinal products, which could increase or prolong their 

therapeutic effect and adverse reactions. Co-administration of darunavir and ritonavir with medicinal 

products primarily metabolised by CYP2C9 (such as warfarin) and CYP2C19 (such as methadone) 

may result in decreased systemic exposure to such medicinal products, which could decrease or 

shorten their therapeutic effect. 

 

Although the effect on CYP2C8 has only been studied in vitro, co-administration of darunavir and 

ritonavir and medicinal products primarily metabolised by CYP2C8 (such as paclitaxel, rosiglitazone, 

repaglinide) may result in decreased systemic exposure to such medicinal products, which could 

decrease or shorten their therapeutic effect. 

 

Ritonavir inhibits the transporters P-glycoprotein, OATP1B1 and OATP1B3, and co-administration 

with substrates of these transporters can result in increased plasma concentrations of these compounds 

(e.g. dabigatran etexilate, digoxin, statins and bosentan; see the Interaction table below). 

 

Medicinal products that affect darunavir/ritonavir exposure 

Darunavir and ritonavir are metabolised by CYP3A. Medicinal products that induce CYP3A activity 

would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma 

concentrations of darunavir and ritonavir (e.g. rifampicin, St John’s wort, lopinavir). 

Co-administration of darunavir and ritonavir and other medicinal products that inhibit CYP3A may 

decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of 

darunavir and ritonavir (e.g. indinavir, azole antifungals like clotrimazole). These interactions are 

described in the interaction table below. 

 

Interaction table 

Interactions between darunavir/ritonavir and antiretroviral and non-antiretroviral medicinal products 

are listed in the table below. The direction of the arrow for each pharmacokinetic parameter is based on 

the 90% confidence interval of the geometric mean ratio being within (↔), below (↓) or above (↑) the 

80-125% range (not determined as “ND”). 

 

Several of the interaction studies (indicated by # in the table below) have been performed at lower than 

recommended doses of darunavir or with a different dosing regimen (see section 4.2 Posology). The 

effects on co-administered medicinal products may thus be underestimated and clinical monitoring of 

safety may be indicated. 

 

The below list of examples of drug drug interactions is not comprehensive and therefore the label of 

each drug that is co-administered with darunavir should be consulted for information related to the 

route of metabolism, interaction pathways, potential risks, and specific actions to be taken with regards 

to co-administration. 

 
INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS 

Medicinal products by 

therapeutic areas 

Interaction Geometric mean change 

(%) 

Recommendations concerning co-

administration 

HIV ANTIRETROVIRALS 

Integrase strand transfer inhibitors 

Dolutegravir dolutegravir AUC ↓ 22% 

dolutegravir C24h  ↓ 38%  

dolutegravir Cmax ↓ 11% 

darunavir ↔* 

* Using cross-study comparisons to 

historical pharmacokinetic data 

Darunavir co-administered with 

low dose ritonavir and dolutegravir 

can be used without dose 

adjustment. 

Raltegravir Some clinical studies suggest 

raltegravir may cause a modest 

decrease in darunavir plasma 

concentrations. 

At present the effect of raltegravir 

on darunavir plasma 

concentrations does not appear to 

be clinically relevant. Darunavir 

co-administered with low dose 



10 

 

ritonavir and raltegravir can be 

used without dose adjustments. 

Nucleo(s/t)ide reverse transcriptase inhibitors (NRTIs) 

Didanosine 

400 mg once daily 

didanosine AUC ↓ 9% 

didanosine Cmin ND  

didanosine Cmax ↓ 16%  

darunavir AUC ↔  

darunavir Cmin ↔  

darunavir Cmax ↔ 

Darunavir co-administered with 

low dose ritonavir and didanosine 

can be used without dose 

adjustments. 

Didanosine is to be administered 

on an empty stomach, thus it 

should be administered 1 hour 

before or 2 hours after 

darunavir/ritonavir given with 

food. 

Tenofovir disoproxil 

245 mg once daily‡ 

tenofovir AUC ↑ 22% 

tenofovir Cmin ↑ 37% 

tenofovir Cmax ↑ 24% 
#darunavir AUC ↑ 21% 
#darunavir Cmin ↑ 24% 
#darunavir Cmax ↑ 16% 

(↑ tenofovir from effect on MDR-1 

transport in the renal tubules) 

Monitoring of renal function may 

be indicated when darunavir co-

administered with low dose 

ritonavir is given in combination 

with tenofovir disoproxil, 

particularly in patients with 

underlying systemic or renal 

disease, or in patients taking 

nephrotoxic agents. 

Emtricitabine/tenofovir 

alafenamide 

Tenofovir alafenamide ↔ 

Tenofovir ↑ 

 

The recommended dose of 

emtricitabine/tenofovir 

alafenamide is 200/10 mg once 

daily when used with darunavir 

with low dose ritonavir. 

Abacavir 

Emtricitabine 

Lamivudine 

Stavudine 

Zidovudine 

Not studied. Based on the different 

elimination pathways of the other 

NRTIs zidovudine, emtricitabine, 

stavudine, lamivudine, that are 

primarily renally excreted, and 

abacavir for which metabolism is not 

mediated by CYP450, no interactions 

are expected for these medicinal 

compounds and darunavir co-

administered with low dose ritonavir. 

Darunavir co-administered with 

low dose ritonavir can be used 

with these NRTIs without dose 

adjustment. 

Non-nucleo(s/t)ide reverse transcriptase inhibitors (NNRTIs) 

Efavirenz 

600 mg once daily 

efavirenz AUC ↑ 21%  

efavirenz Cmin ↑ 17%  

efavirenz Cmax ↑ 15%  
#darunavir AUC ↓ 13% 
#darunavir Cmin ↓ 31% 
#darunavir Cmax ↓ 15% 

(↑ efavirenz from CYP3A inhibition) 

(↓ darunavir from CYP3A induction) 

Clinical monitoring for central 

nervous system toxicity associated 

with increased exposure to 

efavirenz may be indicated when 

darunavir co-administered with 

low dose ritonavir is given in 

combination with efavirenz. 

 

Efavirenz in combination with 

darunavir/ritonavir 800/100 mg 

once daily may result in sub-

optimal darunavir Cmin. If 

efavirenz is to be used in 

combination with 

darunavir/ritonavir, the 

darunavir/ritonavir 600/100 mg 

twice daily regimen should be used 

(see section 4.4). 

Etravirine 

100 mg twice daily 

etravirine AUC ↓ 37% 

etravirine Cmin ↓ 49%  

etravirine Cmax ↓ 32%  

darunavir AUC ↑ 15%  

darunavir Cmin ↔  

darunavir Cmax ↔ 

Darunavir co-administered with 

low dose ritonavir and etravirine 

200 mg twice daily can be used 

without dose adjustments. 



11 

 

Nevirapine 

200 mg twice daily 

nevirapine AUC ↑ 27% 

nevirapine Cmin ↑ 47% 

nevirapine Cmax ↑ 18% 
#darunavir: concentrations were 

consistent with historical data 

(↑ nevirapine from CYP3A inhibition) 

Darunavir co-administered with 

low dose ritonavir and nevirapine 

can be used without dose 

adjustments. 

Rilpivirine 

150 mg once daily 

rilpivirine AUC ↑ 130% 

rilpivirine Cmin ↑ 178% 

rilpivirine Cmax ↑ 79%  

darunavir AUC ↔  

darunavir Cmin ↓ 11%  

darunavir Cmax ↔ 

Darunavir co-administered with 

low dose ritonavir and rilpivirine 

can be used without dose 

adjustments. 

HIV Protease inhibitors (PIs) - without additional co-administration of low dose ritonavir† 

Atazanavir 

300 mg once daily 

atazanavir AUC ↔  

atazanavir Cmin ↑ 52% 

atazanavir Cmax ↓ 11% 
#darunavir AUC ↔ 
#darunavir Cmin ↔ 
#darunavir Cmax ↔ 

 

Atazanavir: comparison of 

atazanavir/ritonavir 300/100 mg once 

daily vs. atazanavir 300 mg once daily 

in combination with 

darunavir/ritonavir 400/100 mg twice 

daily.  

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg twice 

daily vs. darunavir/ritonavir 

400/100 mg twice daily in 

combination with atazanavir 300 mg 

once daily. 

Darunavir co-administered with 

low dose ritonavir and atazanavir 

can be used without dose 

adjustments. 

Indinavir 

800 mg twice daily 

indinavir AUC ↑ 23%  

indinavir Cmin ↑ 125% 

indinavir Cmax ↔ 
#darunavir AUC ↑ 24% 
#darunavir Cmin ↑ 44% 
#darunavir Cmax ↑ 11% 

 

Indinavir: comparison of 

indinavir/ritonavir 800/100 mg twice 

daily vs. indinavir/darunavir/ritonavir 

800/400/100 mg twice daily. 

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg twice 

daily vs. darunavir/ritonavir 

400/100 mg in combination with 

indinavir 800 mg twice daily. 

When used in combination with 

darunavir co-administered with 

low dose ritonavir, dose 

adjustment of indinavir from 

800 mg twice daily to 600 mg 

twice daily may be warranted in 

case of intolerance. 

Saquinavir 

1,000 mg twice daily 

#darunavir AUC ↓ 26% 
#darunavir Cmin ↓ 42% 
#darunavir Cmax ↓ 17% 

saquinavir AUC ↓ 6%  

saquinavir Cmin ↓ 18%  

saquinavir Cmax ↓ 6% 

 

Saquinavir: comparison of 

saquinavir/ritonavir 1,000/100 mg 

twice daily vs. 

saquinavir/darunavir/ritonavir 

1,000/400/100 mg twice daily. 

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg twice 

It is not recommended to combine 

darunavir co-administered with 

low dose ritonavir with saquinavir. 



12 

 

daily vs. darunavir/ritonavir 

400/100 mg in combination with 

saquinavir 1,000 mg twice daily. 

HIV Protease inhibitors (PIs) - with co-administration of low dose ritonavir† 

Lopinavir/ritonavir 

400/100 mg twice daily 

 

 

 

 

Lopinavir/ritonavir 

533/133.3 mg twice daily 

lopinavir AUC ↑ 9% 

lopinavir Cmin ↑ 23%  

lopinavir Cmax ↓ 2%  

darunavir AUC ↓ 38%‡  

darunavir Cmin ↓ 51%‡  

darunavir Cmax ↓ 21%‡  

lopinavir AUC ↔  

lopinavir Cmin ↑ 13%  

lopinavir Cmax ↑ 11%  

darunavir AUC ↓ 41%  

darunavir Cmin ↓ 55%  

darunavir Cmax ↓ 21% 
‡ based upon non dose normalised 

values 

Due to a decrease in the exposure 

(AUC) of darunavir by 40%, 

appropriate doses of the 

combination have not been 

established. Hence, concomitant 

use of darunavir co-administered 

with low dose ritonavir and the 

combination product 

lopinavir/ritonavir is 

contraindicated (see section 4.3). 

CCR5 ANTAGONIST 

Maraviroc 

150 mg twice daily 

maraviroc AUC ↑ 305% 

maraviroc Cmin ND 

maraviroc Cmax ↑ 129% 

darunavir, ritonavir concentrations 

were consistent with historical data 

The maraviroc dose should be 

150 mg twice daily when co-

administered with darunavir with 

low dose ritonavir. 

α1-ADRENORECEPTOR ANTAGONIST 

Alfuzosin Based on theoretical considerations 

darunavir is expected to increase 

alfuzosin plasma concentrations. 

(CYP3A inhibition) 

Co-administration of darunavir 

with low dose ritonavir and 

alfuzosin is contraindicated (see 

section 4.3). 

ANAESTHETIC 

Alfentanil Not studied. The metabolism of 

alfentanil is mediated via CYP3A, and 

may as such be inhibited by darunavir 

co-administered with low dose 

ritonavir. 

The concomitant use with 

darunavir and low dose ritonavir 

may require to lower the dose of 

alfentanil and requires monitoring 

for risks of prolonged or delayed 

respiratory depression. 

ANTIANGINA/ANTIARRHYTHMIC 

Disopyramide 

Flecainide 

Lidocaine 

(systemic) 

Mexiletine 

Propafenone 

 

 

Amiodarone 

Bepridil 

Dronedarone 

Ivabradine, 

Quinidine 

Ranolazine 

Not studied. Darunavir is expected to 

increase these antiarrhythmic plasma 

concentrations. 

(CYP3A and/or CYP2D6 inhibition) 

Caution is warranted and 

therapeutic concentration 

monitoring, if available, is 

recommended for these 

antiarrhythmics when co-

administered with darunavir with 

low dose ritonavir. 

 

Darunavir co-administered with 

low dose ritonavir and 

amiodarone, bepridil, dronedarone, 

ivabradine, quinidine, or 

ranolazine is contraindicated (see 

section 4.3). 

Digoxin 

0.4 mg single dose 

digoxin AUC ↑ 61% 

digoxin Cmin ND 

digoxin Cmax ↑ 29% 

(↑ digoxin from probable inhibition of 

P-gp) 

Given that digoxin has a narrow 

therapeutic index, it is 

recommended that the lowest 

possible dose of digoxin should 

initially be prescribed in case 

digoxin is given to patients on 

darunavir/ritonavir therapy. The 

digoxin dose should be carefully 

titrated to obtain the desired 



13 

 

clinical effect while assessing the 

overall clinical state of the subject. 

ANTIBIOTIC 

Clarithromycin 

500 mg twice daily 

clarithromycin AUC ↑ 57% 

clarithromycin Cmin ↑ 174% 

clarithromycin Cmax ↑ 26% 
#darunavir AUC ↓ 13% 
#darunavir Cmin ↑ 1% 
#darunavir Cmax ↓ 17% 

14-OH-clarithromycin concentrations 

were not detectable when combined 

with darunavir/ritonavir. 

(↑ clarithromycin from CYP3A 

inhibition and possible P-gp 

inhibition) 

Caution should be exercised when 

clarithromycin is combined with 

darunavir co-administered with 

low dose ritonavir. 

 

For patients with renal impairment 

the Summary of Product 

Characteristics for clarithromycin 

should be consulted for the 

recommended dose. 

ANTICOAGULANT/PLATELET AGGREGATION INHIBITOR 

Apixaban 

Edoxaban 

Rivaroxaban 

Not studied. Co-administration of 

darunavir with these anticoagulants 

may increase concentrations of the 

anticoagulant, which may lead to an 

increased bleeding risk. 

(CYP3A and/or P-gp inhibition). 

The use of darunavir co-

administered with low dose 

ritonavir and these anticoagulants 

is not recommended. 

Dabigatran 

Ticagrelor 

Not studied. Co-administration with 

boosted darunavir may lead to a 

substantial increase in exposure to 

dabigatran or ticagrelor. 

Concomitant administration of 

boosted darunavir with 

dabigatran or ticagrelor is 

contraindicated (see section 4.3). 

 

Use of other antiplatelets not 

affected by CYP inhibition or 

induction (e.g. prasugrel) is 

recommended. 

Warfarin Not studied. Warfarin concentrations 

may be affected when co-administered 

with darunavir with low dose 

ritonavir. 

It is recommended that the 

international normalised ratio 

(INR) be monitored when warfarin 

is combined with darunavir co-

administered with low dose 

ritonavir. 

ANTICONVULSANTS 

Phenobarbital 

Phenytoin 

Not studied. Phenobarbital and 

phenytoin are expected to decrease 

plasma concentrations of darunavir 
and its pharmacoenhancer.  

(induction of CYP450 enzymes) 

Darunavir co-administered with 

low dose ritonavir should not be 

used in combination with these 

medicines. 

Carbamazepine 

200 mg twice daily 

carbamazepine AUC ↑ 45% 

carbamazepine Cmin ↑ 54%  

carbamazepine Cmax ↑ 43%  

darunavir AUC ↔  

darunavir Cmin ↓ 15%  

darunavir Cmax ↔ 

No dose adjustment for 

darunavir/ritonavir is 

recommended. If there is a need to 

combine darunavir/ritonavir and 

carbamazepine, patients should be 

monitored for potential 

carbamazepine-related adverse 

events. Carbamazepine 

concentrations should be 

monitored and its dose should be 

titrated for adequate response. 

Based upon the findings, the 

carbamazepine dose may need to 

be reduced by 25% to 50% in the 

presence of darunavir/ritonavir. 

Clonazepam Not studied. Co administration of 

boosted darunavir with clonazepam 

may increase concentrations of 

clonazepam. (CYP3A inhibition) 

Clinical monitoring is 

recommended when co 

administering darunavir with low 

dose ritonavir and clonazepam. 



14 

 

ANTIDEPRESSANTS 

Paroxetine 

20 mg once daily 

 

 

 

 

Sertraline 

50 mg once daily 

 

 

 

 

 

 

 

 

 

 

 

 

 

Amitriptyline 

Desipramine 

Imipramine 

Nortriptyline 

Trazodone 

paroxetine AUC ↓ 39% 

paroxetine Cmin ↓ 37% 

paroxetine Cmax ↓ 36% 
#darunavir AUC ↔ 
#darunavir Cmin ↔ 
#darunavir Cmax ↔ 

sertraline AUC ↓ 49% 

sertraline Cmin ↓ 49% 

sertraline Cmax ↓ 44% 
#darunavir AUC ↔ 
#darunavir Cmin ↓ 6% 
#darunavir Cmax ↔ 

 

 

 

Concomitant use of darunavir co-

administered with low dose ritonavir 

and these antidepressants may 

increase concentrations of the 

antidepressant. (CYP2D6 and/or 

CYP3A inhibition) 

If antidepressants are co-

administered with darunavir with 

low dose ritonavir, the 

recommended approach is a dose 

titration of the antidepressant 

based on a clinical assessment of 

antidepressant response. In 

addition, patients on a stable dose 

of these antidepressants who start 

treatment with darunavir with low 

dose ritonavir should be monitored 

for antidepressant response. 

 

Clinical monitoring is 

recommended when co-

administering darunavir with low 

dose ritonavir with these 

antidepressants and a dose 

adjustment of the antidepressant 

may be needed. 

ANTIEMETICS 

Domperidone Not studied. Co-administration of 

domperidone with boosted 

darunavir is contraindicated. 
ANTIFUNGALS 

Voriconazole Not studied. Ritonavir may decrease 

plasma concentrations of 

voriconazole. (induction of CYP450 

enzymes) 

Voriconazole should not be 

combined with darunavir co-

administered with low dose 

ritonavir unless an assessment of 

the benefit/risk ratio justifies the 

use of voriconazole. 

Fluconazole 

Isavuconazole 

Itraconazole 

Posaconazole 

 

 

Clotrimazole 

 

Not studied. Darunavir may increase 

antifungal plasma concentrations and 

posaconazole, isavuconazole, 

itraconazole, or fluconazole may 

increase darunavir concentrations. 

(CYP3A and/or P-gp inhibition) 

 

Not studied. Concomitant systemic 

use of clotrimazole and darunavir 

co-administered with low dose 

ritonavir may increase plasma 

concentrations of darunavir and/or 

clotrimazole.  

Darunavir AUC24h ↑ 33% (based on 

population pharmacokinetic model) 

 

Caution is warranted and clinical 

monitoring is recommended. When 

co-administration is required the 

daily dose of itraconazole should 

not exceed 200 mg. 

ANTIGOUT MEDICINES 

Colchicine Not studied. Concomitant use of 

colchicine and darunavir co-

administered with low dose ritonavir 

may increase the exposure to 

colchicine. 

(CYP3A and/ or P-gp inhibition) 

A reduction in colchicine dosage 

or an interruption of colchicine 

treatment is recommended in 

patients with normal renal or 

hepatic function if treatment with 

darunavir co-administered with 

low dose ritonavir is required. For 



15 

 

patients with renal or hepatic 

impairment colchicine with 

darunavir co-administered with 

low dose ritonavir is 

contraindicated (see sections 4.3 

and 4.4). 

ANTIMALARIALS 

Artemether/Lumefantrine 

80/480 mg, 6 doses at 0, 8, 24, 

36, 48, and 60 hours 

artemether AUC ↓ 16% 

artemether Cmin ↔  

artemether Cmax ↓ 18%  

dihydroartemisinin AUC ↓ 18%  

dihydroartemisinin Cmin ↔  

dihydroartemisinin Cmax ↓ 18%  

lumefantrine AUC ↑ 175%  

lumefantrine Cmin ↑ 126%  

lumefantrine Cmax ↑ 65%  

darunavir AUC ↔ 

darunavir Cmin ↓ 13% 

darunavir Cmax ↔ 

The combination of darunavir and 

artemether/lumefantrine can be 

used without dose adjustments; 

however, due to the increase in 

lumefantrine exposure, the 

combination should be used with 

caution. 

ANTIMYCOBACTERIALS 

Rifampicin 

Rifapentine 

Not studied. Rifapentine and 

rifampicin are strong CYP3A inducers 

and have been shown to cause 

profound decreases in concentrations 

of other protease inhibitors, which can 

result in virological failure and 

resistance development (CYP450 

enzyme induction). During attempts to 

overcome the decreased exposure by 

increasing the dose of other protease 

inhibitors with low dose ritonavir, a 

high frequency of liver reactions was 

seen with rifampicin. 

The combination of rifapentine and 

darunavir with concomitant low 

dose ritonavir is not recommended. 

 

The combination of rifampicin and 

darunavir with concomitant low 

dose ritonavir is contraindicated 

(see section 4.3). 

Rifabutin 

150 mg once every other 

day 

rifabutin AUC** ↑ 55% 

rifabutin Cmin** ↑ ND 

rifabutin Cmax** ↔ 

darunavir AUC ↑ 53% 

darunavir Cmin ↑ 68% 

darunavir Cmax ↑ 39% 
** sum of active moieties of rifabutin 

(parent drug + 25-O-desacetyl 

metabolite) 

 

The interaction trial showed a 

comparable daily systemic exposure 

for rifabutin between treatment at 

300 mg once daily alone and 150 mg 

once every other day in combination 

with darunavir/ritonavir (600/100 mg 

twice daily) with an about 10-fold 

increase in the daily exposure to the 

active metabolite 

25-O-desacetylrifabutin. Furthermore, 

AUC of the sum of active moieties of 

rifabutin (parent drug + 25-O-

desacetyl metabolite) was increased 

1.6-fold, while Cmax remained 

comparable. 

Data on comparison with a 150 mg 

once daily reference dose is lacking. 

 

A dosage reduction of rifabutin by 

75% of the usual dose of 

300 mg/day (i.e. rifabutin 150 mg 

once every other day) and 

increased monitoring for rifabutin 

related adverse events is warranted 

in patients receiving the 

combination with darunavir co-

administered with ritonavir. In 

case of safety issues, a further 

increase of the dosing interval for 

rifabutin and/or monitoring of 

rifabutin levels should be 

considered. 

Consideration should be given to 

official guidance on the 

appropriate treatment of 

tuberculosis in HIV infected 

patients. 

Based upon the safety profile of 

darunavir/ritonavir, the increase in 

darunavir exposure in the presence 

of rifabutin does not warrant a 

dose adjustment for 

darunavir/ritonavir. 

Based on pharmacokinetic 

modeling, this dosage reduction of 

75% is also applicable if patients 



16 

 

(Rifabutin is an inducer and substrate 

of CYP3A.) An increase of systemic 

exposure to darunavir was observed 

when darunavir co-administered with 

100 mg ritonavir was co-administered 

with rifabutin (150 mg once every 

other day). 

receive rifabutin at doses other 

than 300 mg/day. 

ANTINEOPLASTICS 

Dasatinib 

Nilotinib 

Vinblastine 

Vincristine 

 

 

 

 

 

 

 

 

 

Everolimus 

Irinotecan 

Not studied. Darunavir is expected to 

increase these antineoplastic plasma 

concentrations. 

(CYP3A inhibition) 

Concentrations of these medicinal 

products may be increased when 

co-administered with darunavir 

with low dose ritonavir resulting in 

the potential for increased adverse 

events usually associated with 

these agents. 

Caution should be exercised when 

combining one of these 

antineoplastic agents with 

darunavir with low dose ritonavir. 

 

Concominant use of everolimus or 

Irinotecan and darunavir co-

administered with low dose 

ritonavir is not recommended. 

ANTIPSYCHOTICS/NEUROLEPTICS 

Quetiapine Not studied. Darunavir is expected to 

increase these antipsychotic plasma 

concentrations. 

(CYP3A inhibition) 

Concomitant administration of 

darunavir with low dose ritonavir 

and quetiapine is contraindicated 

as it may increase quetiapine-

related toxicity. Increased 

concentrations of quetiapine may 

lead to coma (see section 4.3). 

Perphenazine 

Risperidone 

Thioridazine 

 

 

 

 

Lurasidone 

Pimozide 

Sertindole 

Not studied. Darunavir is expected to 

increase these antipsychotic plasma 

concentrations. 

(CYP3A, CYP2D6 and/or P-gp 

inhibition) 

A dose decrease may be needed for 

these drugs when co-administered 

with darunavir co-administered 

with low dose ritonavir. 

 

Concominant administration of 

darunavir with low dose ritonavir 

and lurasidone, pimozide or 

sertindole is contraindicated (see 

section 4.3). 

β-BLOCKERS 

Carvedilol 

Metoprolol 

Timolol 

Not studied. Darunavir is expected to 

increase these β-blocker plasma 

concentrations. 

(CYP2D6 inhibition) 

Clinical monitoring is 

recommended when co-

administering darunavir with β-

blockers. A lower dose of the β-

blocker should be considered. 

CALCIUM CHANNEL BLOCKERS 

Amlodipine 

Diltiazem 

Felodipine 

Nicardipine 

Nifedipine 

Verapamil 

Not studied. Darunavir co-

administered with low dose ritonavir 

can be expected to increase the plasma 

concentrations of calcium channel 

blockers. 

(CYP3A and/or CYP2D6 inhibition) 

Clinical monitoring of therapeutic 

and adverse effects is 

recommended when these 

medicines are concomitantly 

administered with darunavir with 

low dose ritonavir. 

CORTICOSTEROIDS 

Corticosteroids primarily 

metabolised by CYP3A 

(including betamethasone, 

budesonide, fluticasone, 

mometasone, prednisone, 

triamcinolone) 

Fluticasone: in a clinical study where 

ritonavir 100 mg capsules twice daily 

were co-administered with 50 μg 

intranasal fluticasone propionate 

(4 times daily) for 7 days in healthy 

subjects, fluticasone propionate plasma 

Concomitant use of darunavir with 

low dose ritonavir and 

corticosteroids that are 

metabolised by CYP3A (e.g. 

fluticasone propionate or other 

inhaled or nasal corticosteroids) 



17 

 

concentrations increased significantly, 

whereas the intrinsic cortisol levels 

decreased by approximately 86% (90% 

CI 82-89%). Greater effects may be 

expected when fluticasone 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. 

The effects of high fluticasone systemic 

exposure on ritonavir plasma levels are 

unknown. 

 

Other corticosteroids: interaction not 

studied. Plasma concentrations of these 

medicinal products may be increased 

when co-administered with darunavir 

with low dose ritonavir, resulting in 

reduced serum cortisol concentrations. 

may increase the risk of 

development of systemic 

corticosteroid effects, including 

Cushing’s syndrome and adrenal 

suppression.  

Co-administration with CYP3A-

metabolised corticosteroids is not 

recommended unless the potential 

benefit to the patient outweighs the 

risk, in which case patients should 

be monitored for systemic 

corticosteroid effects. 

Alternative corticosteroids which 

are less dependent on CYP3A 

metabolism e.g. beclomethasone 

for intranasal or inhalational use 

should be considered, particularly 

for long term use. 

Dexamethasone 

(systemic) 

Not studied. Dexamethasone may 

decrease plasma concentrations of 

darunavir. (CYP3A induction) 

Systemic dexamethasone should be 

used with caution when combined 

with darunavir co-administered 

with low dose ritonavir. 

ENDOTHELIN RECEPTOR ANTAGONISTS 

Bosentan Not studied. Concomitant use of 

bosentan and darunavir co-

administered with low dose ritonavir 

may increase plasma concentrations of 

bosentan. 

Bosentan is expected to decrease 

plasma concentrations of darunavir 

and/or its pharmacoenhancer. 

(CYP3A induction) 

When administered concomitantly 

with darunavir and low dose 

ritonavir, the patient’s tolerability 

of bosentan should be monitored. 

HEPATITIS C VIRUS (HCV) DIRECT-ACTING ANTIVIRALS 

NS3-4A protease inhibitors 

Elbasvir/grazoprevir Darunavir with low dose ritonavir may 

increase the exposure to grazoprevir. 

(CYP3A and OATP1B inhibition). 

Concomitant use of darunavir with 

low dose ritonavir and 

elbasvir/grazoprevir is 

contraindicated (see section 4.3). 

Boceprevir 

800 mg three times daily 

boceprevir AUC ↓ 32% 

boceprevir Cmin ↓ 35%  

boceprevir Cmax ↓ 25%  

darunavir AUC ↓ 44%  

darunavir Cmin ↓ 59%  

darunavir Cmax ↓ 36% 

It is not recommended to co-

administer darunavir with low dose 

ritonavir and boceprevir. 

Glecaprevir/pibrentasvir Based on theoretical considerations 

boosted darunavir may increase the 

exposure to glecaprevir and 

pibrentasvir. 

(P-gp, BCRP and/or OATP1B1/3 

inhibition) 

It is not recommended to 

co-administer boosted darunavir 

with glecaprevir/pibrentasvir. 

Simeprevir simeprevir AUC ↑ 159% 

simeprevir Cmin ↑ 358%  

simeprevir Cmax ↑ 79%  

darunavir AUC ↑ 18%  

darunavir Cmin ↑ 31%  

darunavir Cmax ↔ 

 

The dose of simeprevir in this 

interaction study was 50 mg when co-

administered in combination with 

It is not recommended to co-

administer darunavir with low dose 

ritonavir and simeprevir. 



18 

 

darunavir/ritonavir, compared to 

150 mg in the simeprevir alone 

treatment group. 

HERBAL PRODUCTS 

St John's wort 

(Hypericum perforatum) 

Not studied. St John’s wort is 

expected to decrease the plasma 

concentrations of darunavir and 

ritonavir. 

(CYP450 induction) 

Darunavir co-administered with 

low dose ritonavir must not be 

used concomitantly with products 

containing St John’s wort 

(Hypericum perforatum) (see 

section 4.3). If a patient is already 

taking St John’s wort, stop St 

John’s wort and if possible check 

viral levels. Darunavir exposure 

(and also ritonavir exposure) may 

increase on stopping St John’s 

wort. The inducing effect may 

persist for at least 2 weeks after 

cessation of treatment with St 

John’s wort. 

HMG CO-A REDUCTASE INHIBITORS 

Lovastatin 

Simvastatin 

Not studied. Lovastatin and 

simvastatin are expected to have 

markedly increased plasma 

concentrations when co-administered 

with darunavir co-administered with 

low dose ritonavir. (CYP3A 

inhibition) 

Increased plasma concentrations of 

lovastatin or simvastatin may 

cause myopathy, including 

rhabdomyolysis. Concomitant use 

of darunavir co-administered with 

low dose ritonavir with lovastatin 

and simvastatin is therefore 

contraindicated (see section 4.3). 

Atorvastatin 

10 mg once daily 

atorvastatin AUC ↑ 3-4 fold 

atorvastatin Cmin ↑ ≈5.5-10 fold  

atorvastatin Cmax ↑ ≈2 fold 
#darunavir/ritonavir 

When administration of 

atorvastatin and darunavir co-

administered with low dose 

ritonavir is desired, it is 

recommended to start with an 

atorvastatin dose of 10 mg once 

daily. A gradual dose increase of 

atorvastatin may be tailored to the 

clinical response. 

Pravastatin 

40 mg single dose 

pravastatin AUC ↑ 81%¶ 

pravastatin Cmin ND 

pravastatin Cmax ↑ 63% 
¶ an up to five-fold increase was seen 

in a limited subset of subjects 

When administration of pravastatin 

and darunavir co-administered 

with low dose ritonavir is required, 

it is recommended to start with the 

lowest possible dose of pravastatin 

and titrate up to the desired clinical 

effect while monitoring for safety. 

Rosuvastatin 

10 mg once daily 

rosuvastatin AUC ↑ 48%║ 

rosuvastatin Cmax ↑ 144%║ 
║ based on published data with 
darunavir/ritonavir 

When administration of 

rosuvastatin and darunavir co-

administered with low dose 

ritonavir is required, it is 

recommended to start with the 

lowest possible dose of 

rosuvastatin and titrate up to the 

desired clinical effect while 

monitoring for safety. 

OTHER LIPID MODIFYING AGENTS 

Lomitapide Based on theoretical considerations 

boosted darunavir is expected to 

increase the exposure of lomitapide 

when co-administered.  

(CYP3A inhibition) 

Co-administration is 

contraindicated (see section 4.3) 

H2-RECEPTOR ANTAGONISTS 

Ranitidine 

150 mg twice daily 

#darunavir AUC ↔ 
#darunavir Cmin ↔ 

Darunavir co-administered with 

low dose ritonavir can be co-



19 

 

#darunavir Cmax ↔ administered with H2-receptor 

antagonists without dose 

adjustments. 

IMMUNOSUPPRESSANTS 

Ciclosporin 

Sirolimus 

Tacrolimus 

 

 

Everolimus 

Not studied. Exposure to these 

immunosuppressants will be increased 

when co-administered with darunavir 

co-administered with low dose 

ritonavir. (CYP3A inhibition) 

Therapeutic drug monitoring of the 

immunosuppressive agent must be 

done when co-administration 

occurs. 

 

Concomitant use of everolimus 

and darunavir co-administered 

with low dose ritonavir is not 

recommended. 

INHALED BETA AGONISTS 

Salmeterol Not studied. Concomitant use of 

salmeterol and darunavir co-

administered with low dose ritonavir 

may increase plasma concentrations of 

salmeterol. 

Concomitant use of salmeterol and 

darunavir co-administered with 

low dose ritonavir is not 

recommended. The combination 

may result in increased risk of 

cardiovascular adverse event with 

salmeterol, including QT 

prolongation, palpitations and 

sinus tachycardia. 

NARCOTIC ANALGESICS / TREATMENT OF OPIOID DEPENDENCE 

Methadone 

individual dose ranging 

from 55 mg to 150 mg 

once daily 

R(-) methadone AUC ↓ 16% 

R(-) methadone Cmin ↓ 15%  

R(-) methadone Cmax ↓ 24% 

No adjustment of methadone 

dosage is required when initiating 

co-administration with 

darunavir/ritonavir. However, 

increased methadone dose may be 

necessary when concomitantly 

administered for a longer period of 

time due to induction of 

metabolism by ritonavir. 

Therefore, clinical monitoring is 

recommended, as maintenance 

therapy may need to be adjusted in 

some patients. 

Buprenorphine/naloxone 

8/2 mg–16/4 mg once 

daily 

buprenorphine AUC ↓ 11% 

buprenorphine Cmin ↔  

buprenorphine Cmax ↓ 8%  

norbuprenorphine AUC ↑ 46%  

norbuprenorphine Cmin ↑ 71%  

norbuprenorphine Cmax ↑ 36%  

naloxone AUC ↔ 

naloxone Cmin ND 

naloxone Cmax ↔ 

The clinical relevance of the 

increase in norbuprenorphine 

pharmacokinetic parameters has 

not been established. Dose 

adjustment for buprenorphine may 

not be necessary when co-

administered with 

darunavir/ritonavir but a careful 

clinical monitoring for signs of 

opiate toxicity is recommended. 

Fentanyl 

Oxycodone 

Tramadol 

Based on theoretical considerations 

boosted darunavir may increase 

plasma concentrations of these 

analgesics. 

(CYP2D6 and/or CYP3A inhibition) 

Clinical monitoring is 

recommended when 

co-administering duranavir with 

low dose ritonavir with these 

analgesics. 

OESTROGEN-BASED CONTRACEPTIVES 

Drospirenone Ethinylestradiol 

(3 mg/0.02 mg once daily) 

 

 

 

 

 

Ethinylestradiol 

Norethindrone 

Not studied with darunavir/ritonavir. 

 

 

 

 

 

 

ethinylestradiol AUC ↓ 44% β 

ethinylestradiol Cmin ↓ 62% β 

When darunavir is coadministered 

with a drospirenone-containing 

product, clinical monitoring is 

recommended due to the potential 

for hyperkalaemia. 

 

Alternative or additional 

contraceptive measures are 

recommended when oestrogen-



20 

 

35 μg/1 mg once daily ethinylestradiol Cmax ↓ 32% β 

norethindrone AUC ↓ 14% β 

norethindrone Cmin ↓ 30% β 

norethindrone Cmax ↔ β 

β with darunavir/ritonavir 

based contraceptives are co-

administered with darunavir and 

low dose ritonavir.  

 

Patients using oestrogens as 

hormone replacement therapy 

should be clinically monitored for 

signs of oestrogen deficiency. 

OPIOID ANTAGONIST 

Naloxegol Not studied. Co-administration of boosted 

darunavir and naloxegol is 

contraindicated. 

PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS 

For the treatment of erectile 

dysfunction 

Avanafil 

Sildenafil 

Tadalafil 

Vardenafil 

In an interaction study #, a comparable 

systemic exposure to sildenafil was 

observed for a single intake of 100 mg 

sildenafil alone and a single intake of 

25 mg sildenafil co-administered with 

darunavir and low dose ritonavir. 

The combination of avanafil and 

darunavir with low dose ritonavir 

is contraindicated (see section 4.3). 

Concomitant use of other PDE-5 

inhibitors for the treatment of 

erectile dysfunction with darunavir 

co-administered with low dose 

ritonavir should be done with 

caution. If concomitant use of 

darunavir co-administered with 

low dose ritonavir with sildenafil, 

vardenafil or tadalafil is indicated, 

sildenafil at a single dose not 

exceeding 25 mg in 48 hours, 

vardenafil at a single dose not 

exceeding 2.5 mg in 72 hours or 

tadalafil at a single dose not 

exceeding 10 mg in 72 hours is 

recommended. 

For the treatment of 

pulmonary arterial 

hypertension 

Sildenafil 

Tadalafil 

Not studied. Concomitant use of 

sildenafil or tadalafil for the treatment 

of pulmonary arterial hypertension and 

darunavir co-administered with low 

dose ritonavir may increase plasma 

concentrations of sildenafil or tadalafil. 

(CYP3A inhibition) 

A safe and effective dose of 

sildenafil for the treatment of 

pulmonary arterial hypertension 

co-administered with darunavir 

and low dose ritonavir has not 

been established. There is an 

increased potential for sildenafil-

associated adverse events 

(including visual disturbances, 

hypotension, prolonged erection 

and syncope). Therefore, co-

administration of darunavir with 

low dose ritonavir and sildenafil 

when used for the treatment of 

pulmonary arterial hypertension is 

contraindicated (see section 4.3). 

Co-administration of tadalafil for 

the treatment of pulmonary arterial 

hypertension with darunavir and 

low dose ritonavir is not 

recommended. 

PROTON PUMP INHIBITORS 

Omeprazole 

20 mg once daily 

#darunavir AUC ↔ 
#darunavir Cmin ↔ 
#darunavir Cmax ↔ 

Darunavir co-administered with 

low dose ritonavir can be co-

administered with proton pump 

inhibitors without dose 

adjustments. 

SEDATIVES/HYPNOTICS 

Buspirone 

Clorazepate 

Not studied. Sedative/hypnotics are 

extensively metabolised by CYP3A. 

Clinical monitoring is 

recommended when co-



21 

 

Diazepam 

Estazolam 

Flurazepam 

Midazolam 

(parenteral) 

Zoldipem 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Midazolam (oral) 

Triazolam 

Co-administration with 

darunavir/ritonavir may cause a large 

increase in the concentration of these 

medicines. 

 

 

 

If parenteral midazolam is co-

administered with darunavir co-

administered with low dose ritonavir it 

may cause a large increase in the 

concentration of this benzodiazepine. 

Data from concomitant use of 

parenteral midazolam with other 

protease inhibitors suggest a possible 

3-4 fold increase in midazolam plasma 

levels. 

administering darunavir with these 

sedatives/hypnotics and a lower 

dose of the sedatives/hypnotics 

should be considered.  

 

If parenteral midazolam is co-

administered with darunavir with 

low dose ritonavir, 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. Dose adjustment for 

midazolam should be considered, 

especially if more than a single 

dose of midazolam is 

administered.  

 

 

Darunavir co-administered with 

low dose ritonavir is 

contraindicated with triazolam or 

oral midazolam (see section 4.3). 

 

TREATMENT FOR PREMATURE EJACULATION 

Dapoxetine Not studied. Co-administration of boosted 

darunavir with dapoxetine is 

contraindicated. 

UROLOGICAL DRUGS 

Fesoterodine 

Solifenacin 

Not studied. Use with caution. Monitor for 

fesoterodine or solifenacin adverse 

reactions, dose reduction of 

fesoterodine or solifenacin may be 

necessary. 
# Studies have been performed at lower than recommended doses of darunavir or with a different dosing regimen (see 

section 4.2 Posology). 

† The efficacy and safety of the use of darunavir with 100 mg ritonavir and any other HIV PI (e.g. (fos)amprenavir, 

nelfinavir and tipranavir) has not been established in HIV patients. According to current treatment guidelines, dual 

therapy with protease inhibitors is generally not recommended. 
‡ Study was conducted with tenofovir disoproxil fumarate 300 mg once daily. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in 

pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, 

the animal data as well as the clinical experience in pregnant women should be taken into account. 

 

There are no adequate and well controlled studies on pregnancy outcome with darunavir in pregnant 

women. Studies in animals do not indicate direct harmful effects with respect to pregnancy, 

embryonal/foetal development, parturition or postnatal development (see section 5.3). 

 

Darunavir co-administered with low dose ritonavir should be used during pregnancy only if the 

potential benefit justifies the potential risk. 

 

Breast-feeding 

 



22 

 

It is not known whether darunavir is excreted in human milk. Studies in rats have demonstrated that 

darunavir is excreted in milk and at high levels (1,000 mg/kg/day) resulted in toxicity. Because of both 

the potential for HIV transmission and the potential for adverse reactions in breast-fed infants, mothers 

should be instructed not to breast-feed under any circumstances if they are receiving darunavir. 

 

Fertility 

 

No human data on the effect of darunavir on fertility are available. There was no effect on mating or 

fertility with darunavir treatment in rats (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Darunavir in combination with ritonavir has no or negligible influence on the ability to drive and use 

machines. However, dizziness has been reported in some patients during treatment with regimens 

containing darunavir co-administered with low dose ritonavir and should be borne in mind when 

considering a patient’s ability to drive or operate machinery (see section 4.8). 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

During the clinical development program (N=2,613 treatment-experienced subjects who initiated 

therapy with darunavir/ ritonavir 600/100 mg twice daily), 51.3% of subjects experienced at least one 

adverse reaction. The total mean treatment duration for subjects was 95.3 weeks. The most frequent 

adverse reactions reported in clinical trials and as spontaneous reports are diarrhoea, nausea, rash, 

headache and vomiting. The most frequent serious reactions are acute renal failure, myocardial 

infarction, immune reconstitution inflammatory syndrome, thrombocytopenia, osteonecrosis, 

diarrhoea, hepatitis and pyrexia. 

 

In the 96 week analysis, the safety profile of darunavir/ ritonavir 800/100 mg once daily in treatment-

naïve subjects was similar to that seen with darunavir/ ritonavir 600/100 mg twice daily in treatment-

experienced subjects except for nausea which was observed more frequently in treatment-naïve 

subjects. This was driven by mild intensity nausea. No new safety findings were identified in the 

192 week analysis of the treatment-naïve subjects in which the mean treatment duration of darunavir/ 

ritonavir 800/100 mg once daily was 162.5 weeks. 

 

Tabulated list of adverse reactions 

 

Adverse reactions are listed by system organ class (SOC) and frequency category. Within each 

frequency category, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as follows: 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) and not known (frequency cannot be 

estimated from the available data). 

 

Adverse reactions observed with darunavir/ritonavir in clinical trials and post-marketing 

 

MedDRA system organ class 

Frequency category  

Adverse reaction 

Infections and infestations 

Uncommon herpes simplex 

Blood and lymphatic system disorders 

Uncommon 

 

 

Rare 

thrombocytopenia, neutropenia, anaemia, 

leucopenia 

 

increased eosinophil count 

Immune system disorders 



23 

 

Uncommon immune reconstitution inflammatory syndrome, 

(drug) hypersensitivity 

Endocrine disorders 

Uncommon hypothyroidism, increased blood thyroid 

stimulating hormone 

Metabolism and nutrition disorders 

Common 

 

 

 

 

Uncommon 

diabetes mellitus, hypertriglyceridaemia, 

hypercholesterolaemia, hyperlipidaemia 

 

gout, anorexia, decreased appetite, decreased 

weight, increased weight, hyperglycaemia, 

insulin resistance, decreased high density 

lipoprotein, increased appetite, polydipsia, 

increased blood lactate dehydrogenase 

Psychiatric disorders 

Common 

 

 

Uncommon 

 

 

 

Rare 

insomnia 

 

depression, disorientation, anxiety, sleep 

disorder, abnormal dreams, nightmare, decreased 

libido 

 

confusional state, altered mood, restlessness 

Nervous system disorders 

Common 

 

Uncommon 

 

 

 

Rare 

headache, peripheral neuropathy, dizziness 

 

lethargy, paraesthesia, hypoaesthesia, dysgeusia, 

disturbance in attention, memory impairment, 

somnolence 

 

syncope, convulsion, ageusia, sleep phase rhythm 

disturbance 

Eye disorders 

Uncommon 

 

Rare 

conjunctival hyperaemia, dry eye 

 

visual disturbance 

Ear and labyrinth disorders 

Uncommon vertigo 

Cardiac disorders 

Uncommon 

 

 

Rare 

myocardial infarction, angina pectoris, prolonged 

electrocardiogram QT, tachycardia 

 

acute myocardial infarction, sinus bradycardia, 

palpitations 

Vascular disorders 

Uncommon hypertension, flushing 

Respiratory, thoracic and mediastinal disorders 

Uncommon 

 

Rare 

dyspnoea, cough, epistaxis, throat irritation 

 

rhinorrhoea 

Gastrointestinal disorders 

Very common 

 

Common 

 

 

diarrhoea 

 

vomiting, nausea, abdominal pain, increased 

blood amylase, dyspepsia, abdominal distension, 

flatulence 



24 

 

 

Uncommon 

 

 

 

 

Rare 

 

pancreatitis, gastritis, gastrooesophageal reflux 

disease, aphthous stomatitis, retching, dry mouth, 

abdominal discomfort, constipation, increased 

lipase, eructation, oral dysaesthesia 

 

stomatitis, haematemesis, cheilitis, dry lip, coated 

tongue 

Hepatobiliary disorders 

Common 

 

Uncommon 

increased alanine aminotransferase 

 

hepatitis, cytolytic hepatitis, hepatic steatosis, 

hepatomegaly, increased transaminase, increased 

aspartate aminotransferase, increased blood 

bilirubin, increased blood alkaline phosphatase, 

increased gamma-glutamyltransferase 

Skin and subcutaneous tissue disorders 

Common 

 

 

 

Uncommon 

 

 

 

 

Rare 

 

 

 

Not known 

rash (including macular, maculopapular, papular, 

erythematous and pruritic rash), pruritus 

 

angioedema, generalised rash, allergic dermatitis, 

urticaria, eczema, erythema, hyperhidrosis, night 

sweats, alopecia, acne, dry skin, nail 

pigmentation 

 

DRESS, Stevens-Johnson syndrome, erythema 

multiforme, dermatitis, seborrhoeic dermatitis, 

skin lesion, xeroderma 

 

toxic epidermal necrolysis, acute generalised 

exanthematous pustulosis 

Musculoskeletal and connective tissue disorders 

Uncommon 

 

 

 

 

Rare 

myalgia, osteonecrosis, muscle spasms, muscular 

weakness, arthralgia, pain in extremity, 

osteoporosis, increased blood creatine 

phosphokinase 

 

musculoskeletal stiffness, arthritis, joint stiffness 

Renal and urinary disorders 

Uncommon 

 

 

 

Rare 

acute renal failure, renal failure, nephrolithiasis, 

increased blood creatinine, proteinuria, 

bilirubinuria, dysuria, nocturia, pollakiuria 

 

decreased creatinine renal clearance 

Reproductive system and breast disorders 

Uncommon erectile dysfunction, gynaecomastia 

General disorders and administration site conditions 

Common 

 

Uncommon 

 

 

Rare 

asthenia, fatigue 

 

pyrexia, chest pain, peripheral oedema, malaise, 

feeling hot, irritability, pain 

 

chills, abnormal feeling, xerosis 
 
Description of selected adverse reactions 

 



25 

 

Rash 

In clinical trials, rash was mostly mild to moderate, often occurring within the first four weeks of 

treatment and resolving with continued dosing. In cases of severe skin reaction see the warning in 

section 4.4. 

 

During the clinical development program of raltegravir in treatment-experienced patients, rash, 

irrespective of causality, was more commonly observed with regimens containing darunavir/ritonavir 

+ raltegravir compared to those containing darunavir/ritonavir without raltegravir or raltegravir 

without darunavir/ritonavir. Rash considered by the investigator to be drug-related occurred at similar 

rates. The exposure-adjusted rates of rash (all causality) were 10.9, 4.2, and 3.8 per 100 patient-years 

(PYR), respectively; and for drug-related rash were 2.4, 1.1, and 2.3 per 100 PYR, respectively. The 

rashes observed in clinical studies were mild to moderate in severity and did not result in 

discontinuation of therapy (see section 4.4). 

 

Metabolic parameters 

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

4.4). 

 

Musculoskeletal abnormalities 

Increased CPK, myalgia, myositis and rarely, rhabdomyolysis have been reported with the use of 

protease inhibitors, particularly in combination with NRTIs. 

 

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). 

 

Immune reconstitution inflammatory syndrome 

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). 

 

Bleeding in haemophiliac patients 

There have been reports of increased spontaneous bleeding in haemophiliac patients receiving 

antiretroviral protease inhibitors (see section 4.4). 

 

Paediatric population 

 

The safety assessment in paediatric patients is based on the 48-week analysis of safety data from three 

Phase II trials. The following patient populations were evaluated (see section 5.1): 

● 80 ART-experienced HIV-1 infected paediatric patients aged from 6 to 17 years and weighing at 

least 20 kg who received darunavir tablets with low dose ritonavir twice daily in combination 

with other antiretroviral agents. 

● 21 ART-experienced HIV-1 infected paediatric patients aged from 3 to < 6 years and weighing 

10 kg to < 20 kg (16 participants from 15 kg to < 20 kg) who received darunavir oral suspension 

with low dose ritonavir twice daily in combination with other antiretroviral agents. 

● 12 ART-naïve HIV-1 infected paediatric patients aged from 12 to 17 years and weighing at least 

40 kg who received darunavir tablets with low dose ritonavir once daily in combination with 

other antiretroviral agents (see section 5.1). 

 

Overall, the safety profile in these paediatric patients was similar to that observed in the adult 

population. 

 

Other special populations 

 

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



26 

 

Among 1,968 treatment-experienced patients receiving darunavir co-administered with ritonavir 

600/100 mg twice daily, 236 patients were co-infected with hepatitis B or C. Co-infected patients were 

more likely to have baseline and treatment emergent hepatic transaminase elevations than those 

without chronic viral hepatitis (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 darunavir co-administered with low dose ritonavir is 

limited. Single doses up to 3,200 mg of darunavir as oral solution alone and up to 1,600 mg of the 

tablet formulation of darunavir in combination with ritonavir have been administered to healthy 

volunteers without untoward symptomatic effects. 

 

There is no specific antidote for overdose with darunavir. Treatment of overdose with darunavir 

consists of general supportive measures including monitoring of vital signs and observation of the 

clinical status of the patient. Since darunavir is highly protein bound, dialysis is unlikely to be 

beneficial in significant removal of the active substance. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antivirals for systemic use, protease inhibitors, ATC code: J05AE10. 

 

Mechanism of action 

 

Darunavir is an inhibitor of the dimerisation and of the catalytic activity of the HIV-1 protease (KD of 

4.5 x 10-12M). It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus 

infected cells, thereby preventing the formation of mature infectious virus particles. 

 

Antiviral activity in vitro 

 

Darunavir exhibits activity against laboratory strains and clinical isolates of HIV-1 and laboratory 

strains of HIV-2 in acutely infected T-cell lines, human peripheral blood mononuclear cells and human 

monocytes/macrophages with median EC50 values ranging from 1.2 to 8.5 nM (0.7 to 5.0 ng/ml). 

Darunavir demonstrates antiviral activity in vitro against a broad panel of HIV-1 group M (A, B, C, D, 

E, F, G) and group O primary isolates with EC50 values ranging from < 0.1 to 4.3 nM. 

 

These EC50 values are well below the 50% cellular toxicity concentration range of 87 µM to > 

100 µM. 

 

Resistance 

 

In vitro selection of darunavir-resistant virus from wild type HIV-1 was lengthy (> 3 years). 

The selected viruses were unable to grow in the presence of darunavir concentrations above 

400 nM. 

Viruses selected in these conditions and showing decreased susceptibility to darunavir (range: 

23-50-fold) harboured 2 to 4 amino acid substitutions in the protease gene. The decreased 

susceptibility to darunavir of the emerging viruses in the selection experiment could not be explained 

by the emergence of these protease mutations. 

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


27 

 

 

The clinical trial data from ART-experienced patients (TITAN trial and the pooled analysis of the 

POWER 1, 2 and 3 and DUET 1 and 2 trials) showed that virologic response to darunavir co-

administered with low dose ritonavir was decreased when 3 or more darunavir RAMs (V11I, V32I, 

L33F, I47V, I50V, I54L or M, T74P, L76V, I84V and L89V) were present at baseline or when these 

mutations developed during treatment. 

 

Increasing baseline darunavir fold change in EC50 (FC) was associated with decreasing virologic 

response. A lower and upper clinical cut-off of 10 and 40 were identified. Isolates with baseline 

FC ≤ 10 are susceptible; isolates with FC > 10 to 40 have decreased susceptibility; isolates with 

FC > 40 are resistant (see Clinical results). 

 

Viruses isolated from patients on darunavir/ritonavir 600/100 mg twice daily experiencing 

virologic failure by rebound that were susceptible to tipranavir at baseline remained susceptible 

to tipranavir after treatment in the vast majority of cases. 

 

The lowest rates of developing resistant HIV virus are observed in ART-naïve patients who are 

treated for the first time with darunavir in combination with other ART. 

 

The table below shows the development of HIV 1 protease mutations and loss of susceptibility 

to PIs in virologic failures at endpoint in the ARTEMIS, ODIN and TITAN trials. 

 

 ARTEMIS 
Week 192 

ODIN 
Week 48 

TITAN 
Week 48 

 Darunavir/ 
ritonavir 

800/100 mg 

once daily  

N=343 

Darunavir/ 
ritonavir 

800/100 mg once 

daily  

N=294 

Darunavir/ ritonavir 

600/100 mg twice 

daily N=296 

Darunavir/ 
ritonavir 

600/100 mg 

twice daily  

N=298 

Total number of virologic 
failuresa, n (%) 

Rebounders 

Never suppressed 

subjects 

 
55 (16.0%) 

 

39 (11.4%) 

16 (4.7%) 

 
65 (22.1%) 

 

11 (3.7%) 

54 (18.4%) 

 
54 (18.2%) 

 

11 (3.7%) 

43 (14.5%) 

 
31 (10.4%) 

 

16 (5.4%) 

15 (5.0%) 

Number of subjects with virologic failure and paired baseline/endpoint genotypes, developing mutationsb at 
endpoint, n/N 

Primary (major) PI 

Mutations 

0/43 1/60 0/42 6/28 

PI RAMs 4/43 7/60 4/42 10/28 

Number of subjects with virologic failure and paired baseline/endpoint phenotypes, showing loss of 

susceptibility to PIs at endpoint compared to baseline, n/N 

PI 

darunavir  

amprenavir  

atazanavir  

indinavir  

lopinavir  

saquinavir  

tipranavir 

 

0/39 

0/39 

0/39 

0/39 
0/39 

0/39 

0/39 

 

1/58 

1/58 

2/56 

2/57 
1/58 

0/56 

0/58 

 

0/41 

0/40 

0/40 

0/40 
0/40 

0/40 

0/41 

 

3/26 

0/22 

0/22 

1/24 
0/23 

0/22 

1/25 
a TLOVR non-VF censored algorithm based on HIV-1 RNA < 50 copies/ml, except for TITAN (HIV-1 RNA < 

400 copies/ml) 
b IAS-USA lists 

 

Cross-resistance 

 

Darunavir FC was less than 10 for 90% of 3,309 clinical isolates resistant to amprenavir, atazanavir, 

indinavir, lopinavir, nelfinavir, ritonavir, saquinavir and/or tipranavir showing that viruses resistant to 

most PIs remain susceptible to darunavir. 

 



28 

 

In the virologic failures of the ARTEMIS trial no cross-resistance with other PIs was observed.  

 

Clinical results 

 

Adult patients 

For clinical trial results in ART-naïve adult patients, refer to the Summary of Product Characteristics 

for darunavir 400 mg and 800 mg tablets. 

 

Efficacy of darunavir 600 mg twice daily co-administered with 100 mg ritonavir twice daily in ART-

experienced patients 

 

The evidence of efficacy of darunavir co-administered with ritonavir (600/100 mg twice daily) in 

ART-experienced patients is based on the 96 weeks analysis of the Phase III trial TITAN in 

ART-experienced lopinavir naïve patients, on the 48 week analysis of the Phase III trial ODIN in 

ART-experienced patients with no DRV-RAMs, and on the analyses of 96 weeks data from the Phase 

IIb trials POWER 1 and 2 in ART-experienced patients with high level of PI resistance. 

 

TITAN is a randomised, controlled, open-label Phase III trial comparing darunavir co-administered 

with ritonavir (600/100 mg twice daily) versus lopinavir/ritonavir (400/100 mg twice daily) in ART-

experienced, lopinavir naïve HIV-1 infected adult patients. Both arms used an Optimised Background 

Regimen (OBR) consisting of at least 2 antiretrovirals (NRTIs with or without NNRTIs). 

 

The table below shows the efficacy data of the 48 week analysis from the TITAN trial. 

 

TITAN 

Outcomes Darunavir/ritonavir 

600/100 mg twice 

daily + OBR 

N=298 

Lopinavir/ ritonavir 

400/100 mg twice daily 

+ OBR 

N=297 

Treatment difference 

(95% CI of difference) 

HIV-1 RNA 

< 50 copies/mla 

70.8% (211) 60.3% (179) 10.5% (2.9; 18.1)b 

median CD4+ cell 

count change from 

baseline (x 106/l)c 

88 81  

a Imputations according to the TLOVR algorithm 
b Based on a normal approximation of the difference in % response 
c NC=F 

 

At 48 weeks non-inferiority in virologic response to the darunavir/ritonavir treatment, defined as the 

percentage of patients with plasma HIV-1 RNA level < 400 and < 50 copies/ml, was demonstrated (at 

the pre-defined 12% non-inferiority margin) for both ITT and OP populations. These results were 

confirmed in the analysis of data at 96 weeks of treatment in the TITAN trial, with 60.4% of patients in 

the darunavir/ritonavir arm having HIV-1 RNA < 50 copies/ml at week 96 compared to 55.2% in the 

lopinavir/ritonavir arm [difference: 5.2%, 95% CI (-2.8; 13.1)]. 

 

ODIN is a Phase III, randomised, open-label trial comparing darunavir/ritonavir 800/100 mg once 

daily versus darunavir/ritonavir 600/100 mg twice daily in ART-experienced HIV-1 infected patients 

with screening genotype resistance testing showing no darunavir RAMs (i.e. V11I, V32I, L33F, I47V, 

I50V, I54M, I54L, T74P, L76V, I84V, L89V) and a screening HIV-1 RNA > 1,000 copies/ml. 

Efficacy analysis is based on 48 weeks of treatment (see table below). Both arms used an optimised 

background regimen (OBR) of ≥ 2 NRTIs. 

 

ODIN 
Outcomes Darunavir/ritonavir 

800/100 mg once daily 

+ OBR 

N=294 

Darunavir/ritonavir 

600/100 mg twice daily 

+ OBR 

N=296 

Treatment difference 

(95% CI of difference) 



29 

 

HIV-1 RNA 

< 50 copies/mla 

With Baseline HIV-1 

RNA (copies/ml) 

< 100,000 

≥ 100,000 

With Baseline CD4+ 

cell count (x 106/l) 

≥ 100 

< 100 

With HIV-1 clade 

Type B  

Type AE  

Type C  

Otherc 

72.1% (212) 

 

 

 

77.6% (198/255) 

35.9% (14/39) 

 

 

75.1% (184/245) 

57.1% (28/49) 

 

70.4% (126/179) 

90.5% (38/42) 

72.7% (32/44) 

55.2% (16/29) 

70.9% (210) 

 

 

 

73.2% (194/265) 

51.6% (16/31) 

 

 

72.5% (187/258) 

60.5% (23/38) 

 

64.3% (128/199) 

91.2% (31/34) 

78.8% (26/33) 

83.3% (25/30) 

1.2% (-6.1; 8.5)b 

 

 

 

4.4% (-3.0; 11.9) 

-15.7% (-39.2; 7.7) 

 

 

2.6% (-5.1; 10.3) 

-3.4% (-24.5; 17.8) 

 

6.1% (-3.4; 15.6) 

-0.7% (-14.0; 12.6) 

-6.1% (-2.6; 13.7) 

-28.2% (-51.0; -5.3) 

mean CD4+ cell count 

change from baseline (x 

106/l)e 

108 112 -5d (-25; 16) 

a Imputations according to the TLOVR algorithm 
b Based on a normal approximation of the difference in % response 
c Clades A1, D, F1, G, K, CRF02_AG, CRF12_BF, and CRF06_CPX 
d Difference in means 
e Last Observation Carried Forward imputation 

 

At 48 weeks, virologic response, defined as the percentage of patients with plasma HIV-1 RNA level 

< 50 copies/ml, with darunavir/ritonavir 800/100 mg once daily treatment was demonstrated to be 

non-inferior (at the pre-defined 12% non-inferiority margin) compared to darunavir/ritonavir 

600/100 mg twice daily for both ITT and OP populations. 

 

Darunavir/ritonavir 800/100 mg once daily in ART-experienced patients should not be used in patients 

with one or more darunavir resistance associated mutations (DRV-RAMs) or HIV-1 RNA ≥ 100,000 

copies/ml or CD4+ cell count < 100 cells x 106/l (see sections 4.2 and 4.4). Limited data is available in 

patients with HIV-1 clades other than B. 

 

POWER 1 and POWER 2 are randomised, controlled trials comparing darunavir co-administered with 

ritonavir (600/100 mg twice daily) with a control group receiving an investigator-selected PI(s) 

regimen in HIV-1 infected patients who had previously failed more than 1 PI containing regimen. An 

OBR consisting of at least 2 NRTIs with or without enfuvirtide (ENF) was used in both trials. 

 

The table below shows the efficacy data of the 48-week and 96-week analyses from the pooled 

POWER 1 and POWER 2 trials. 

 
POWER 1 and POWER 2 pooled data 

 Week 48 Week 96 

Outcomes Darunavir/ 

ritonavir 

600/100 mg 

twice daily 

n=131 

Control  

n=124 

Treatment 

difference 

Darunavir/ 

ritonavir 

600/100 mg 

twice daily 

n=131 

Control 

n=124 

Treatment 

difference 

HIV RNA 

< 50 copies/mla 

45.0% 

(59) 

11.3% 

(14) 

33.7% 

(23.4%; 

44.1%)c 

38.9% 

(51) 

8.9% 

(11) 

30.1% 

(20.1; 40.0)c 

CD4+ cell 

count mean 

change from 

baseline  

(x 106/l)b 

103 17 86 

(57; 114)c 

133 15 118 

(83.9; 153.4)c 

a Imputations according to the TLOVR algorithm 
b Last Observation Carried Forward imputation 
c 95% confidence intervals. 



30 

 

 

Analyses of data through 96 weeks of treatment in the POWER trials demonstrated sustained 

antiretroviral efficacy and immunologic benefit. 

 

Out of the 59 patients who responded with complete viral suppression (< 50 copies/ml) at week 48, 

47 patients (80% of the responders at week 48) remained responders at week 96. 

 

Baseline genotype or phenotype and virologic outcome 

Baseline genotype and darunavir FC (shift in susceptibility relative to reference) were shown to be a 

predictive factor of virologic outcome. 

 

Proportion (%) of patients with response (HIV-1 RNA < 50 copies/ml at week 24) to darunavir co-

administered with ritonavir (600/100 mg twice daily) by baseline genotypea, and baseline darunavir 

FC and by use of enfuvirtide (ENF): As treated analysis of the POWER and DUET trials. 

 

 Number of baseline mutationsa Baseline DRV FCb 
Response (HIV-1 

RNA < 50 copies/ml 

at week 24) 

%, n/N 

All 

ranges 
0-2 3 ≥ 4 

All 

ranges 
≤ 10 10-40 > 40 

All patients 
45% 

455/1,014 

54% 

359/660 

39% 

67/172 

12% 

20/171 

45% 

455/1,014 

55% 

364/659 

29% 

59/203 

8% 

9/118 

Patients with 

no/non-naïve use of 

ENFc 

 

39% 

290/741 

 

50% 

238/477 

 

29% 

35/120 

 

7% 

10/135 

 

39% 

290/741 

 

51% 

244/477 

 

17% 

25/147 

 

5% 

5/94 

Patients with naïve 

use of ENFd 

60% 

165/273 

66% 

121/183 

62% 

32/52 

28% 

10/36 

60% 

165/273 

66% 

120/182 

61% 

34/56 

17% 

4/24 
a Number of mutations from the list of mutations associated with a diminished response to darunavir/ritonavir (V11I, 

V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V or L89V) 
b fold change in EC50 
c “Patients with no/non-naïve use of ENF” are patients who did not use ENF or who used ENF but not for the first time 
d “Patients with naïve use of ENF” are patients who used ENF for the first time 

 

Paediatric patients 

 

For clinical trial results in ART-naïve paediatric patients aged 12 to 17 years, refer to the Summary of 

Product Characteristics for darunavir 400 mg and 800 mg tablets.  

 

ART-experienced paediatric patients from the age of 6 to < 18 years, and weighing at least 20 kg 

 

DELPHI is an open-label, Phase II trial evaluating the pharmacokinetics, safety, tolerability, and 

efficacy of darunavir with low dose ritonavir in 80 ART-experienced HIV-1 infected paediatric 

patients aged 6 to 17 years and weighing at least 20 kg. These patients received darunavir/ritonavir 

twice daily in combination with other antiretroviral agents (see section 4.2 for dosage 

recommendations per body weight). Virologic response was defined as a decrease in plasma HIV-1 

RNA viral load of at least 1.0 log10 versus baseline. 

 

In the study, patients who were at risk of discontinuing therapy due to intolerance of ritonavir oral 

solution (e.g. taste aversion) were allowed to switch to the capsule formulation. Of the 44 patients 

taking ritonavir oral solution, 27 switched to the 100 mg capsule formulation and exceeded the weight-

based ritonavir dose without changes in observed safety. 

 

DELPHI 

Outcomes at week 48 Darunavir/ritonavir 

N=80 

HIV-1 RNA < 50 copies/mla 47.5% (38) 

CD4+ cell count mean change from baselineb 147 
a Imputations according to the TLOVR algorithm. 



31 

 

b 
Non-completer is failure imputation: patients who discontinued prematurely are imputed with a 

change equal to 0. 

 

According to the TLOVR non-virologic failure censored algorithm 24 (30.0%) patients experienced 

virological failure, of which 17 (21.3%) patients were rebounders and 7 (8.8%) patients were non-

responders. 

 

ART-experienced paediatric patients from the age of 3 to < 6 years 

 

The pharmacokinetics, safety, tolerability and efficacy of darunavir/ritonavir twice daily. in 

combination with other antiretroviral agents in 21 ART-experienced HIV-1 infected paediatric patients 

aged 3 to < 6 years and weighing 10 kg to < 20 kg was evaluated in an open-label, Phase II trial, 

ARIEL. Patients received a weight-based twice daily treatment regimen, patients weighing 10 kg to < 

15 kg received darunavir/ritonavir 25/3 mg/kg twice daily, and patients weighing 15 kg to < 20 kg 

received darunavir/ritonavir 375/50 mg twice daily. At week 48, the virologic response, defined as the 

percentage of patients with confirmed plasma viral load < 50 HIV-1 RNA copies/ml, was evaluated in 

16 paediatric patients 15 kg to < 20 kg and 5 paediatric patients 10 kg to < 15 kg receiving 

darunavir/ritonavir in combination with other antiretroviral agents (see section 4.2 for dosage 

recommendations per body weight). 

 

ARIEL 

Outcomes at week 48 Darunavir/ritonavir 

 10 kg to < 15 kg 

N=5 
15 kg to < 20 kg 

N=16 

HIV-1 RNA < 50 copies/mla 80.0% (4) 81.3% (13) 

CD4+ percent change from baselineb 4 4 

CD4+ cell count mean change from baselineb 16 241 

a Imputations according to the TLOVR algorithm. 
b NC=F 

 

Limited efficacy data are available in paediatric patients below 15 kg and no recommendation on a 

posology can be made. 

 

Pregnancy and postpartum 

 

Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a 

background regimen was evaluated in a clinical trial of 36 pregnant women (18 in each arm) during 

the second and third trimesters, and postpartum. Virologic response was preserved throughout the 

study period in both arms. No mother to child transmission occurred in the infants born to the 

31 subjects who stayed on the antiretroviral treatment through delivery. There were no new clinically 

relevant safety findings compared with the known safety profile of darunavir/ritonavir in HIV-1 

infected adults (see sections 4.2, 4.4 and 5.2). 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetic properties of darunavir, co-administered with ritonavir, have been evaluated in 

healthy adult volunteers and in HIV-1 infected patients. Exposure to darunavir was higher in HIV-1 

infected patients than in healthy subjects. The increased exposure to darunavir in HIV-1 infected 

patients compared to healthy subjects may be explained by the higher concentrations of α1-acid 

glycoprotein (AAG) in HIV-1 infected patients, resulting in higher darunavir binding to plasma AAG 

and, therefore, higher plasma concentrations. 

 

Darunavir is primarily metabolised by CYP3A. Ritonavir inhibits CYP3A, thereby increasing the 

plasma concentrations of darunavir considerably. 



32 

 

 

Absorption 

 

Darunavir was rapidly absorbed following oral administration. Maximum plasma concentration of 

darunavir in the presence of low dose ritonavir is generally achieved within 2.5-4.0 hours. 

 

The absolute oral bioavailability of a single 600 mg dose of darunavir alone was approximately 37% 

and increased to approximately 82% in the presence of 100 mg twice daily ritonavir. The overall 

pharmacokinetic enhancement effect by ritonavir was an approximate 14-fold increase in the systemic 

exposure of darunavir when a single dose of 600 mg darunavir was given orally in combination with 

ritonavir at 100 mg twice daily (see section 4.4). 

 

When administered without food, the relative bioavailability of darunavir in the presence of low dose 

ritonavir is 30% lower as compared to intake with food. Therefore, darunavir tablets should be taken 

with ritonavir and with food. The type of food does not affect exposure to darunavir. 

 

Distribution 

 

Darunavir is approximately 95% bound to plasma protein. Darunavir binds primarily to plasma α1-acid 

glycoprotein. 

 

Following intravenous administration, the volume of distribution of darunavir alone was 88.1 ± 59.0 l 

(Mean ± SD) and increased to 131 ± 49.9 l (Mean ± SD) in the presence of 100 mg twice-daily 

ritonavir. 

 

Biotransformation 

 

In vitro experiments with human liver microsomes (HLMs) indicate that darunavir primarily undergoes 

oxidative metabolism. Darunavir is extensively metabolised by the hepatic CYP system and almost 

exclusively by isozyme CYP3A4. A 14C-darunavir trial in healthy volunteers showed that a majority of 

the radioactivity in plasma after a single 400/100 mg darunavir with ritonavir dose was due to the 

parent active substance. At least 3 oxidative metabolites of darunavir have been identified in humans; 

all showed activity that was at least 10-fold less than the activity of darunavir against wild type HIV. 

 

Elimination 

 

After a 400/100 mg 14C-darunavir with ritonavir dose, approximately 79.5% and 13.9% of the 

administered dose of 14C-darunavir could be retrieved in faeces and urine, respectively. Unchanged 

darunavir accounted for approximately 41.2% and 7.7% of the administered dose in faeces and urine, 

respectively. The terminal elimination half-life of darunavir was approximately 15 hours when 

combined with ritonavir. 

The intravenous clearance of darunavir alone (150 mg) and in the presence of low dose ritonavir was 

32.8 l/h and 5.9 l/h, respectively. 

 

Special populations 

 

Paediatric population 

The pharmacokinetics of darunavir in combination with ritonavir taken twice daily in 74 treatment-

experienced paediatric patients, aged 6 to 17 years and weighing at least 20 kg, showed that the 

administered weight-based doses of darunavir/ritonavir resulted in darunavir exposure comparable to 

that in adults receiving darunavir/ritonavir 600/100 mg twice daily (see section 4.2). 

 

The pharmacokinetics of darunavir in combination with ritonavir taken twice daily in 14 treatment-

experienced paediatric patients, aged 3 to < 6 years and weighing at least 15 kg to < 20 kg, showed that 

weight-based dosages resulted in darunavir exposure that was comparable to that achieved in adults 

receiving darunavir/ritonavir 600/100 mg twice daily (see section 4.2). 



33 

 

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 12 ART-naïve 

paediatric patients, aged 12 to < 18 years and weighing at least 40 kg, showed that darunavir/ritonavir 

800/100 mg once daily results in darunavir exposure that was comparable to that achieved in adults 

receiving darunavir/ritonavir 800/100 mg once daily. Therefore the same once daily dosage may be 

used in treatment-experienced adolescents aged 12 to < 18 years and weighing at least 40 kg without 

darunavir resistance associated mutations (DRV-RAMs)* and who have plasma HIV-1 RNA < 100,000 

copies/ml and CD4+ cell count ≥ 100 cells x 106/l (see section 4.2). 
*   DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V 

 

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 10 treatment-

experienced paediatric patients, aged 3 to < 6 years and weighing at least 14 kg to < 20 kg, showed 

that weight-based dosages resulted in darunavir exposure that was comparable to that achieved in 

adults receiving darunavir/ritonavir 800/100 mg once daily (see section 4.2). In addition, 

pharmacokinetic modeling and simulation of darunavir exposures in paediatric patients across the ages 

of 3 to < 18 years confirmed the darunavir exposures as observed in the clinical studies and allowed 

the identification of weight-based darunavir/ritonavir once daily dosing regimens for paediatric 

patients weighing at least 15 kg that are either ART-naïve or treatment-experienced paediatric patients 

without DRV-RAMs* and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count 

≥ 100 cells x 106/l (see section 4.2). 

* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V 

 

Elderly 

Population pharmacokinetic analysis in HIV infected patients showed that darunavir pharmacokinetics 

are not considerably different in the age range (18 to 75 years) evaluated in HIV infected patients 

(n=12, age ≥ 65) (see section 4.4). However, only limited data were available in patients above the age 

of 65 year. 

 

Gender 

Population pharmacokinetic analysis showed a slightly higher darunavir exposure (16.8%) in HIV 

infected females compared to males. This difference is not clinically relevant. 

 

Renal impairment 

Results from a mass balance study with 14C-darunavir with ritonavir showed that approximately 7.7% 

of the administered dose of darunavir is excreted in the urine unchanged. 

 

Although darunavir has not been studied in patients with renal impairment, population 

pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly 

affected in HIV infected patients with moderate renal impairment (CrCl between 30-60 ml/min, n=20) 

(see sections 4.2 and 4.4). 

 

Hepatic impairment 

Darunavir is primarily metabolised and eliminated by the liver. In a multiple dose study with darunavir 

co-administered with ritonavir (600/100 mg) twice daily, it was demonstrated that the total plasma 

concentrations of darunavir in subjects with mild (Child-Pugh Class A, n=8) and moderate (Child-

Pugh Class B, n=8) hepatic impairment were comparable with those in healthy subjects. However, 

unbound darunavir concentrations were approximately 55% (Child-Pugh Class A) and 100% (Child-

Pugh Class B) higher, respectively. The clinical relevance of this increase is unknown therefore, 

darunavir should be used with caution. The effect of severe hepatic impairment on the 

pharmacokinetics of darunavir has not been studied (see sections 4.2, 4.3 and 4.4). 

 

Pregnancy and postpartum 

The exposure to total darunavir and ritonavir after intake of darunavir/ritonavir 600/100 mg twice 

daily and darunavir/ritonavir 800/100 mg once daily as part of an antiretroviral regimen was generally 

lower during pregnancy compared with postpartum. However, for unbound (i.e. active) darunavir, the 

pharmacokinetic parameters were less reduced during pregnancy compared to postpartum, due to an 

increase in the unbound fraction of darunavir during pregnancy compared to postpartum. 

 



34 

 

Pharmacokinetic results of total darunavir after administration of darunavir/ritonavir at 

600/100 mg twice daily as part of an antiretroviral regimen, during the second trimester of 

pregnancy, the third trimester of pregnancy and postpartum 

Pharmacokinetics of 

total darunavir 

(mean ± SD) 

Second trimester of 

pregnancy 

(n=12)a 

Third trimester of 

pregnancy 

(n=12) 

Postpartum  

(6-12 weeks) 

(n=12) 

Cmax, ng/ml 4,668 ± 1,097 5,328 ± 1,631 6,659 ± 2,364 

AUC12h, ng.h/ml 39,370 ± 9,597 45,880 ± 17,360 56,890 ± 26,340 

Cmin, ng/ml 1,922 ± 825 2,661 ± 1,269 2,851 ± 2,216 
a n=11 for AUC12h 

 

Pharmacokinetic results of total darunavir after administration of darunavir/ritonavir at 

800/100 mg once daily as part of an antiretroviral regimen, during the second trimester of 

pregnancy, the third trimester of pregnancy and postpartum 

Pharmacokinetics of 

total darunavir 

(mean ± SD) 

Second trimester of 

pregnancy 

(n=17) 

Third Trimester of 

pregnancy 

(n=15) 

Postpartum  

(6-12 weeks) 

(n=16) 

Cmax, ng/ml 4,964 ± 1,505 5,132 ± 1,198 7,310 ± 1,704 

AUC24h, ng.h/ml 62,289 ± 16,234 61,112 ± 13,790 92,116 ± 29,241 

Cmin, ng/ml 1,248 ± 542 1,075 ± 594 1,473 ± 1,141 

 

In women receiving darunavir/ritonavir 600/100 mg twice daily during the second trimester of 

pregnancy, mean intra-individual values for total darunavir Cmax, AUC12h and Cmin were 28%, 26% and 

26% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total 

darunavir Cmax, AUC12h and Cmin values were 18%, 16% lower and 2% higher, respectively, as 

compared with postpartum. 

 

In women receiving darunavir/ritonavir 800/100 mg once daily during the second trimester of 

pregnancy, mean intra-individual values for total darunavir Cmax, AUC24h and Cmin were 33%, 31% and 

30% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total 

darunavir Cmax, AUC24h and Cmin values were 29%, 32% and 50% lower, respectively, as compared 

with postpartum. 

 

5.3 Preclinical safety data 

 

Animal toxicology studies have been conducted at exposures up to clinical exposure levels with 

darunavir alone, in mice, rats and dogs and in combination with ritonavir in rats and dogs. 

 

In repeated-dose toxicology studies in mice, rats and dogs, there were only limited effects of treatment 

with darunavir. In rodents the target organs identified were the haematopoietic system, the blood 

coagulation system, liver and thyroid. A variable but limited decrease in red blood cell-related 

parameters was observed, together with increases in activated partial thromboplastin time. 

 

Changes were observed in liver (hepatocyte hypertrophy, vacuolation, increased liver enzymes) and 

thyroid (follicular hypertrophy). In the rat, the combination of darunavir with ritonavir lead to a small 

increase in effect on RBC parameters, liver and thyroid and increased incidence of islet fibrosis in the 

pancreas (in male rats only) compared to treatment with darunavir alone. In the dog, no major toxicity 

findings or target organs were identified up to exposures equivalent to clinical exposure at the 

recommended dose. 

 

In a study conducted in rats, the number of corpora lutea and implantations were decreased in the 

presence of maternal toxicity. Otherwise, there were no effects on mating or fertility with darunavir 



35 

 

treatment up to 1,000 mg/kg/day and exposure levels below (AUC-0.5 fold) of that in human at the 

clinically recommended dose. Up to same dose levels, there was no teratogenicity with darunavir in 

rats and rabbits when treated alone nor in mice when treated in combination with ritonavir. The 

exposure levels were lower than those with the recommended clinical dose in humans. In a pre- and 

postnatal development assessment in rats, darunavir with and without ritonavir, caused a transient 

reduction in body weight gain of the offspring pre-weaning and there was a slight delay in the opening 

of eyes and ears. Darunavir in combination with ritonavir caused a reduction in the number of pups 

that exhibited the startle response on day 15 of lactation and a reduced pup survival during lactation. 

These effects may be secondary to pup exposure to the active substance via the milk and/or maternal 

toxicity. No post weaning functions were affected with darunavir alone or in combination with 

ritonavir. In juvenile rats receiving darunavir up to days 23-26, increased mortality was observed with 

convulsions in some animals. Exposure in plasma, liver and brain was considerably higher than in 

adult rats after comparable doses in mg/kg between days 5 and 11 of age. After day 23 of life, the 

exposure was comparable to that in adult rats. The increased exposure was likely at least partly due to 

immaturity of the drug-metabolising enzymes in juvenile animals. No treatment related mortalities 

were noted in juvenile rats dosed at 1,000 mg/kg darunavir (single dose) on day 26 of age or at 

500 mg/kg (repeated dose) from day 23 to 50 of age, and the exposures and toxicity profile were 

comparable to those observed in adult rats. 

 

Due to uncertainties regarding the rate of development of the human blood brain barrier and liver 

enzymes, darunavir with low dose ritonavir should not be used in paediatric patients below 3 years of 

age. 

 

Darunavir was evaluated for carcinogenic potential by oral gavage administration to mice and rats up 

to 104 weeks. Daily doses of 150, 450 and 1,000 mg/kg were administered to mice and doses of 50, 

150 and 500 mg/kg were administered to rats. Dose-related increases in the incidences of 

hepatocellular adenomas and carcinomas were observed in males and females of both species. Thyroid 

follicular cell adenomas were noted in male rats. Administration of darunavir did not cause a 

statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or 

rats. The observed hepatocellular and thyroid tumours in rodents are considered to be of limited 

relevance to humans. Repeated administration of darunavir to rats caused hepatic microsomal enzyme 

induction and increased thyroid hormone elimination, which predispose rats, but not humans, to 

thyroid neoplasms. At the highest tested doses, the systemic exposures (based on AUC) to darunavir 

were between 0.4- and 0.7-fold (mice) and 0.7- and 1-fold (rats), relative to those observed in humans 

at the recommended therapeutic doses. 

 

After 2 years administration of darunavir at exposures at or below the human exposure, kidney changes 

were observed in mice (nephrosis) and rats (chronic progressive nephropathy). 

 

Darunavir was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including bacterial 

reverse mutation (Ames), chromosomal aberration in human lymphocytes and in vivo micronucleus 

test in mice. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Tablet core 

Silica, colloidal anhydrous 

Cellulose microcrystalline 

Crospovidone 

Sodium starch glycolate 

Hypromellose 

Magnesium stearate 

 

Tablet film-coat 



36 

 

Polyvinyl alcohol, partially hydrolysed 

Titanium dioxide (E171) 

Macrogol 

Talc 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years 

In-use shelf life after first opening HDPE bottle: 100 days 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 
 
Darunavir Mylan 75 mg film-coated tablets 

PVC/PE/PVDC-Al blister pack containing 480 tablets and 480x1 tablets. 

Cold form PVC/Al/OPA-Al blister pack containing 480 tablets and 480x1 tablets. 

HDPE bottle pack with a PP screw cap containing 480 tablets. 
 
Darunavir Mylan 150 mg film-coated tablets 
PVC/PE/PVDC-Al blister pack containing 240 tablets and 240x1 tablets. 
Cold form PVC/Al/OPA-Al blister pack containing 240 tablets and 240x1 tablets. 
HDPE bottle pack with a PP screw cap containing 60 and 240 tablets. 
 
Darunavir Mylan 300 mg film-coated tablets 
PVC/PE/PVDC-Al blister pack containing 30, 60 and 120 tablets and 120x1 tablets. 
Cold form PVC/Al/OPA-Al blister pack containing 30, 60 and 120 tablets and 120x1 tablets. 
HDPE bottle pack with a PP screw cap containing 30 and 120 tablets. 
 
Darunavir Mylan 600 mg film-coated tablets 
PVC/PE/PVDC-Al blister pack containing 30 and 60 tablets and 60x1 tablets. 

Cold form PVC/Al/OPA-Al blister pack containing 30 and 60 tablets and 60x1 tablets. 

HDPE bottle pack with a PP screw cap containing 30, 60, 90 tablets. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 
 

No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Darunavir Mylan 75 mg film-coated tablets 



37 

 

EU/1/16/1140/001 

EU/1/16/1140/002 

EU/1/16/1140/003 

EU/1/16/1140/004 

EU/1/16/1140/005 
 
Darunavir Mylan 150 mg film-coated tablets 

EU/1/16/1140/006 

EU/1/16/1140/007 

EU/1/16/1140/008 

EU/1/16/1140/009 

EU/1/16/1140/010 
EU/1/16/1140/011 
 
Darunavir Mylan 300 mg film-coated tablets 

EU/1/16/1140/012 

EU/1/16/1140/013 

EU/1/16/1140/014 

EU/1/16/1140/015 

EU/1/16/1140/016 

EU/1/16/1140/017 

EU/1/16/1140/018 

EU/1/16/1140/019 

EU/1/16/1140/020 

EU/1/16/1140/021 
 
Darunavir Mylan 600 mg film-coated tablets 

EU/1/16/1140/030 

EU/1/16/1140/031 

EU/1/16/1140/032 

EU/1/16/1140/033 

EU/1/16/1140/034 

EU/1/16/1140/035 

EU/1/16/1140/036 

EU/1/16/1140/037 
EU/1/16/1140/038 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 4th January 2017 

 
 
10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

  

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


38 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 400 mg film-coated tablets  

Darunavir Mylan 800 mg film-coated tablets 

 

 

2.  QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Darunavir Mylan 400 mg film-coated tablets 

Each film-coated tablet contains 400 mg of darunavir. 

 

Darunavir Mylan 800 mg film-coated tablets 

Each film-coated tablet contains 800 mg of darunavir. 

 

For the full list of excipients, see section 6.1.  

 

 

3. PHARMACEUTICAL FORM 

 

Darunavir Mylan 400 mg film-coated tablets 

Film-coated tablet  

White to off-white, oval shaped, biconvex film-coated tablets approximately 19.2 mm by 9.6 mm, 

debossed with ‘M’ on one side and ‘DV4’ on the other side. 

 

Darunavir Mylan 800 mg film-coated tablets 

Film-coated tablet. 

White to off-white, oval shaped, biconvex film-coated tablets approximately 21.2 mm by 10.6 mm, 

debossed with ‘M’ on one side and ‘DV8' on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Darunavir co-administered with low dose ritonavir is indicated in combination with other antiretroviral 

medicinal products for the treatment of patients with human immunodeficiency virus (HIV-1) 

infection.  

 

Darunavir co-administered with cobicistat is indicated in combination with other antiretroviral 

medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adult 

patients (see section 4.2).  

 

Darunavir Mylan 400 mg and 800 mg tablets may be used to provide suitable dose regimens for the 

treatment of HIV-1 infection in adult and paediatric patients from the age of 3 years and at least 40 kg 

body weight who are:  

● antiretroviral therapy (ART)-naïve (see section 4.2).  

● ART-experienced with no darunavir resistance associated mutations (DRV-RAMs) and who 

have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l. In 

deciding to initiate treatment with darunavir in such ART-experienced patients, genotypic 

testing should guide the use of darunavir (see sections 4.2, 4.3, 4.4 and 5.1).  

 



39 

 

4.2 Posology and method of administration 

 

Therapy should be initiated by a health care provider experienced in the management of HIV 

infection. After therapy with darunavir has been initiated, patients should be advised not to alter the 

dosage, dose form or discontinue therapy without discussing with their health care provider.  

 

The interaction profile of darunavir depends on whether ritonavir or cobicistat is used as 

pharmacokinetic enhancer. Darunavir may therefore have different contraindications and 

recommendations for concomitant medications depending on whether the compound is boosted with 

ritonavir or cobicistat (see sections 4.3, 4.4 and 4.5).  

 

Posology  

 

Darunavir must always be given orally with cobicistat or low dose ritonavir as a pharmacokinetic 

enhancer and in combination with other antiretroviral medicinal products. The Summary of Product 

Characteristics of cobicistat or ritonavir as appropriate, must therefore be consulted prior to initiation 

of therapy with darunavir. Cobicistat is not indicated for use in twice daily regimens or for use in the 

paediatric population.  

 

ART-naïve adult patients 

The recommended dose regimen is 800 mg once daily with cobicistat 150 mg once daily or ritonavir 

100 mg once daily taken with food. Darunavir 400 mg and 800 mg tablets can be used to construct the 

once daily 800 mg regimen.  

 

ART-experienced adult patients 

The recommended dose regimens are as follows:  

● In ART-experienced patients with no darunavir resistance associated mutations (DRV-RAMs)* 

and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l 

(see section 4.1) a regimen of 800 mg once daily with cobicistat 150 mg once daily or ritonavir 

100 mg once daily taken with food may be used. Darunavir 400 mg and 800 mg tablets can be 

used to construct the once daily 800 mg regimen.  

● In all other ART-experienced patients or if HIV-1 genotype testing is not available, the 

recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken 

with food. See the Summary of Product Characteristics for darunavir 75 mg, 150 mg, 300 mg or 

600 mg tablets.  
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V  

 

ART-naïve paediatric patients (3 to 17 years of age and weighing at least 40 kg) 

The recommended dose regimen is 800 mg once daily with ritonavir 100 mg once daily taken with 

food. The dose of cobicistat to be used with darunavir in children less than 18 years of age has not 

been established.  

 

ART-experienced paediatric patients (3 to 17 years of age and weighing at least 40 kg) 

The dose of cobicistat to be used with darunavir in children less than 18 years of age has not been 

established.  

 

The recommended dose regimens are as follows:  

● In ART-experienced patients without DRV-RAMs* and who have plasma HIV-1 RNA 

< 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l (see section 4.1) a regimen of 

800 mg once daily with ritonavir 100 mg once daily taken with food may be used. Darunavir 

400 mg and 800 mg tablets can be used to construct the once daily 800 mg regimen.  

● In all other ART-experienced patients or if HIV-1 genotype testing is not available, the 

recommended dose regimen described in the Summary of Product Characteristics for darunavir 

75 mg, 150 mg, 300 mg and 600 mg tablets.  
*   DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V  

 



40 

 

Advice on missed doses 

If a once daily dose of darunavir and/or cobicistat or ritonavir is missed within 12 hours of the time it 

is usually taken, patients should be instructed to take the prescribed dose of darunavir and cobicistat or 

ritonavir with food as soon as possible. If this is noticed later than 12 hours after the time it is usually 

taken, the missed dose should not be taken and the patient should resume the usual dosing schedule.  

 

This guidance is based on the half-life of darunavir in the presence of cobicistat or ritonavir and the 

recommended dosing interval of approximately 24 hours.  

 

Special populations 

 

Elderly 

Limited information is available in this population, and therefore, darunavir should be used with 

caution in this age group (see sections 4.4 and 5.2).  

 

Hepatic impairment 

Darunavir is metabolised by the hepatic system. No dose adjustment is recommended in patients with 

mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, however, darunavir 

should be used with caution in these patients. No pharmacokinetic data are available in patients with 

severe hepatic impairment. Severe hepatic impairment could result in an increase of darunavir 

exposure and a worsening of its safety profile. Therefore, darunavir must not be used in patients with 

severe hepatic impairment (Child-Pugh Class C) (see sections 4.3, 4.4 and 5.2).  

 

Renal impairment 

No dose adjustment is required for darunavir/ritonavir in patients with renal impairment (see sections 

4.4 and 5.2). Cobicistat has not been studied in patients receiving dialysis, and, therefore, no 

recommendation can be made for the use of darunavir/cobicistat in these patients.  

 

Cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in serum 

creatinine and modest declines in creatinine clearance. Hence, the use of creatinine clearance as an 

estimate of renal elimination capacity may be misleading. Cobicistat as a pharmacokinetic enhancer of 

darunavir should, therefore, not be initiated in patients with creatine clearance less than 70 ml/min if 

any co-administered agent requires dose adjustment based on creatinine clearance: e.g. emtricitabine, 

lamivudine, tenofovir disoproxil (as fumarate, phosphate or succinate) or adefovir dipovoxil.  

For information on cobicistat, consult the cobicistat Summary of Product Characteristics.  

 

Paediatric population 

Darunavir should not be used in paediatric patients below 3 years of age or less than 15 kg body 

weight (see sections 4.4 and 5.3).  

 

ART-naïve paediatric patients (3 to 17 years of age and weighing at least 40 kg) 

The recommended dose regimen is 800 mg once daily with ritonavir 100 mg once daily taken with 

food. 

 

ART-experienced paediatric patients (3 to 17 years of age and weighing at least 40 kg) 

In ART-experienced patients without DRV-RAMs* and who have plasma HIV-1 RNA  

< 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l, a regimen of 800 mg once daily with 

ritonavir 100 mg once daily taken with food may be used.  

* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V 

 

For dosage recommendations in children, see the Summary of Product Characteristics for darunavir 

75 mg, 150 mg, 300 mg, 600 mg tablets. 

 

The dose of cobicistat to be used with Darunavir has not been established in this patient population. 

 

Pregnancy and postpartum 



41 

 

No dose adjustment is required for darunavir/ritonavir during pregnancy and postpartum. 

Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential 

risk (see sections 4.4, 4.6 and 5.2). 

 

Treatment with darunavir/cobicistat 800/150 mg during pregnancy results in low darunavir exposure 

(see sections 4.4 and 5.2). Therefore, therapy with Darunavir/cobicistat should not be initiated during 

pregnancy, and women who become pregnant during therapy with Darunavir/cobicistat should be 

switched to an alternative regimen (see sections 4.4 and 4.6). Darunavir/ritonavir may be considered as 

an alternative.  

 

Method of administration 

 

Patients should be instructed to take Darunavir Mylan with cobicistat or low dose ritonavir within 

30 minutes after completion of a meal. The type of food does not affect the exposure to darunavir (see 

sections 4.4, 4.5 and 5.2).  

 

4.3 Contraindications 

 

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

 

Patients with severe (Child-Pugh Class C) hepatic impairment.  

 

Concomitant treatment with any of the following medicinal products given the expected decrease in 

plasma concentrations of darunavir, ritonavir and cobicistat and the potential for loss of therapeutic 

effect (see sections 4.4 and 4.5).  

 

Applicable to darunavir boosted with either ritonavir or cobicistat:  

- The combination product lopinavir/ritonavir (see section 4.5).  
- The strong CYP3A inducers rifampicin and herbal preparations containing St John's wort 

(Hypericum perforatum). Co-administration is expected to reduce plasma concentrations of 

darunavir, ritonavir and cobicistat, which could lead to loss of therapeutic effect and possible 

development of resistance (see sections 4.4 and 4.5).  

 

Applicable to darunavir boosted with cobicistat, not when boosted with ritonavir:  

- Darunavir boosted with cobicistat is more sensitive for CYP3A induction than darunavir 
boosted with ritonavir. Concomitant use with strong CYP3A inducers is contraindicated, since 

these may reduce the exposure to cobicistat and darunavir leading to loss of therapeutic effect. 

Strong CYP3A inducers include e.g. carbamazepine, phenobarbital and phenytoin (see sections 

4.4 and 4.5).  

 

Darunavir boosted with either ritonavir or cobicistat inhibits the elimination of active substances that 

are highly dependent on CYP3A for clearance, which results in increased exposure to the co-

administered medicinal product. Therefore, concomitant treatment with such medicinal products for 

which elevated plasma concentrations are associated with serious and/or life-threatening events is 

contraindicated (applies to darunavir boosted with either ritonavir or cobicistat). These active 

substances include e.g.:  

- alfuzosin  
- amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine  
- astemizole, terfenadine  
- colchicine when used in patients with renal and/or hepatic impairment (see section 4.5)  
- ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine)  
- elbasvir/grazoprevir  
- cisapride 
- dapoxetine 
- domperidone 
- naloxegol 
- lurasidone, pimozide, quetiapine, sertindole (see section 4.5)  



42 

 

- triazolam, midazolam administered orally (for caution on parenterally administered midazolam, 
see section 4.5)  

- sildenafil - when used for the treatment of pulmonary arterial hypertension, avanafil  
- simvastatin, lovastatin and lomitapide (see section 4.5)  
- dabigatran, ticagrelor (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.  

 

Regular assessment of virological response is advised. In the setting of lack or loss of virological 

response, resistance testing should be performed.  

 

Darunavir 400 mg or 800 mg must always be given orally with cobicistat or low dose ritonavir as a 

pharmacokinetic enhancer and in combination with other antiretroviral medicinal products (see section 

5.2). The Summary of Product Characteristics of cobicistat or ritonavir as appropriate, must therefore 

be consulted prior to initiation of therapy with darunavir.  

 

Increasing the dose of ritonavir from that recommended in section 4.2 did not significantly affect 

darunavir concentrations. It is not recommended to alter the dose of cobicistat or ritonavir.  

Darunavir binds predominantly to α1-acid glycoprotein. This protein binding is concentration-

dependent indicative for saturation of binding. Therefore, protein displacement of medicinal products 

highly bound to α1-acid glycoprotein cannot be ruled out (see section 4.5).  

 

ART-experienced patients – once daily dosing 

 

Darunavir used in combination with cobicistat or low dose ritonavir once daily in ART-experienced 

patients should not be used in patients with one or more darunavir resistance associated mutations 

(DRV-RAMs) or HIV-1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 106/l (see section 

4.2). Combinations with optimised background regimen (OBRs) other than ≥ 2 NRTIs have not been 

studied in this population. Limited data are available in patients with HIV-1 clades other than B (see 

section 5.1).  

 

Paediatric population 

 

Darunavir is not recommended for use in paediatric patients below 3 years of age or less than 15 kg 

body weight (see sections 4.2 and 5.3).  

 

Pregnancy 

 

Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential 

risk. Caution should be used in pregnant women with concomitant medications which may further 

decrease darunavir exposure (see sections 4.5 and 5.2). 

 

Treatment with darunavir/cobicistat 800/150 mg once daily during the second and third trimester has 

been shown to result in low darunavir exposure, with a reduction of around 90% in Cmin levels (see 

section 5.2). Cobicistat levels decrease and may not provide sufficient boosting. The substantial 

reduction in darunavir exposure may result in virological failure and an increased risk of mother to 

child transmission of HIV infection. Therefore, therapy with Darunavir/cobicistat should not be 

initiated during pregnancy, and women who become pregnant during therapy with  

Darunavir/cobicistat should be switched to an alternative regimen (see sections 4.2 and 4.6). 

Darunavir given with low dose ritonavir may be considered as an alternative.  

 

Elderly 

 



43 

 

As limited information is available on the use of darunavir in patients aged 65 and over, caution 

should be exercised in the administration of darunavir in elderly patients, reflecting the greater 

frequency of decreased hepatic function and of concomitant disease or other therapy (see sections 4.2 

and 5.2).  

 

Severe skin reactions 

 

During the darunavir/ritonavir clinical development program (N=3,063), severe skin reactions, which 

may be accompanied with fever and/or elevations of transaminases, have been reported in 0.4% of 

patients. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) and Stevens-Johnson 

syndrome has been rarely (< 0.1%) reported, and during post-marketing experience toxic epidermal 

necrolysis and acute generalised exanthematous pustulosis have been reported. Darunavir should be 

discontinued immediately if signs or symptoms of severe skin reactions develop. These can include, 

but are not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or 

joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia. 

  

Rash occurred more commonly in treatment-experienced patients receiving regimens containing 

darunavir/ritonavir + raltegravir compared to patients receiving darunavir/ritonavir without raltegravir 

or raltegravir without darunavir (see section 4.8).  

 

Darunavir contains a sulphonamide moiety. Darunavir should be used with caution in patients with a 

known sulphonamide allergy.  

 

Hepatotoxicity 

 

Drug-induced hepatitis (e.g. acute hepatitis, cytolytic hepatitis) has been reported with darunavir. 

During the darunavir/ritonavir clinical development program (N=3,063), hepatitis was reported in 

0.5% of patients receiving combination antiretroviral therapy with darunavir/ritonavir. Patients with 

pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for 

liver function abnormalities including severe and potentially fatal hepatic adverse reactions. In case of 

concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for 

these medicinal products.  

 

Appropriate laboratory testing should be conducted prior to initiating therapy with darunavir used in 

combination with cobicistat or low dose ritonavir and patients should be monitored during treatment. 

Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, 

cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first 

several months of darunavir used in combination with cobicistat or low dose ritonavir treatment.  

 

If there is evidence of new or worsening liver dysfunction (including clinically significant elevation of 

liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver 

tenderness, hepatomegaly) in patients using darunavir used in combination with cobicistat or low dose 

ritonavir, interruption or discontinuation of treatment should be considered promptly.  

 

Patients with coexisting conditions 

 

Hepatic impairment 

The safety and efficacy of darunavir have not been established in patients with severe underlying liver 

disorders and darunavir is therefore contraindicated in patients with severe hepatic impairment. Due to 

an increase in the unbound darunavir plasma concentrations, darunavir should be used with caution in 

patients with mild or moderate hepatic impairment (see sections 4.2, 4.3 and 5.2).  

 

Renal impairment 

No special precautions or dose adjustments for darunavir/ritonavir are required in patients with renal 

impairment. As darunavir and ritonavir are highly bound to plasma proteins, it is unlikely that they 

will be significantly removed by haemodialysis or peritoneal dialysis. Therefore, no special 

precautions or dose adjustments are required in these patients (see sections 4.2 and 5.2). Cobicistat has 



44 

 

not been studied in patients receiving dialysis, therefore, no recommendation can be made for the use 

of darunavir/cobicistat in these patients (see section 4.2).  

 

Cobicistat decreases the estimated creatinine clearance due to inhibition of tubular secretion of 

creatinine. This should be taken into consideration if darunavir with cobicistat is administered to 

patients in whom the estimated creatinine clearance is used to adjust doses of co-administered 

medicinal products (see section 4.2 and cobicistat SmPC). 

  

There are currently inadequate data to determine whether co-administration of tenofovir disoproxil and 

cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that 

include tenofovir disoproxil without cobicistat.  

 

Haemophiliac patients 

There have been reports of increased bleeding, including spontaneous skin haematomas and 

haemarthrosis in patients with haemophilia type A and B treated with PIs. In some patients additional 

factor VIII was given. In more than half of the reported cases, treatment with PIs 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 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. 

 

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.  

 

Immune reconstitution inflammatory syndrome 

 

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 

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

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

examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and 

pneumonia caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii). Any 

inflammatory symptoms should be evaluated and treatment instituted when necessary. In addition, 

reactivation of herpes simplex and herpes zoster has been observed in clinical studies with darunavir 

co-administered with low dose ritonavir.  

 

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

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

these events can occur many months after initiation of treatment (see section 4.8).  

 

Interactions with medicinal products 

 

Several of the interaction studies have been performed with darunavir at lower than recommended 

doses. The effects on co-administered medicinal products may thus be underestimated and clinical 



45 

 

monitoring of safety may be indicated. For full information on interactions with other medicinal 

products see section 4.5. 

 

Pharmacokinetic enhancer and concomitant medications 

Darunavir has different interaction profiles depending on whether the compound is boosted with 

ritonavir or cobicistat:  

- Darunavir boosted with cobicistat is more sensitive for CYP3A induction: concomitant use of 

darunavir/cobicistat and strong CYP3A inducers is therefore contraindicated (see section 4.3), 

and concomitant use with weak to moderate CYP3A inducers is not recommended (see section 

4.5). Concomitant use of darunavir/ritonavir and darunavir/cobicistat with lopinavir/ritonavir, 

rifampicin and herbal products containing St John's wort, Hypericum perforatum, is 

contraindicated (see section 4.5).  

- Unlike ritonavir, cobicistat does not have inducing effects on enzymes or transport proteins (see 

section 4.5). If switching the pharmacoenhancer from ritonavir to cobicistat, caution is required 

during the first two weeks of treatment with darunavir/cobicistat, particularly if doses of any 

concomitantly administered medicinal products have been titrated or adjusted during use of 

ritonavir as a pharmacoenhancer. A dose reduction of the co-administered drug may be needed 

in these cases.  

 

Efavirenz in combination with darunavir  once daily may result in sub-optimal darunavir Cmin. If 

efavirenz is to be used in combination with darunavir, the darunavir/ritonavir 600/100 mg twice daily 

regimen should be used. See the Summary of Product Characteristics for darunavir 75 mg, 150 mg, 

300 mg and 600 mg tablets (see section 4.5).  

 

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and 

strong inhibitors of CYP3A and P-glycoprotein (P-gp; see sections 4.3 and 4.5).  

 

Darunavir Mylan contains sodium 

 

Darunavir Mylan 400 mg and 800 mg film-coated tablets contain less than 1 mmol sodium (23 mg) per 

dose, that is to say essentially ‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

The interaction profile of darunavir may differ depending on whether ritonavir or cobicistat is used as 

pharmacoenhancer. The recommendations given for concomitant use of darunavir and other medicinal 

products may therefore differ depending on whether darunavir is boosted with ritonavir or cobicistat 

(see sections 4.3 and 4.4), and caution is also required during the first time of treatment if switching 

the pharmacoenhancer from ritonavir to cobicistat (see section 4.4).  

 

Medicinal products that affect darunavir exposure (ritonavir as pharmacoenhancer) 

 

Darunavir and ritonavir are metabolised by CYP3A. Medicinal products that induce CYP3A activity 

would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma 

concentrations of these compounds and consequently that of darunavir, leading to loss of therapeutic 

effect and possible development of resistance (see sections 4.3 and 4.4). CYP3A inducers that are 

contraindicated include rifampicin, St John's wort and lopinavir.  

 

Co-administration of darunavir and ritonavir with other medicinal products that inhibit CYP3A may 

decrease the clearance of darunavir and ritonavir, which may result in increased plasma concentrations 

of darunavir and ritonavir. Co-administration with strong CYP3A4 inhibitors is not recommended and 

caution is warranted, these interactions are described in the interaction table below (e.g. indinavir, 

azole antifungals like clotrimazole).  

 

Medicinal products that affect darunavir exposure (cobicistat as pharmacoenhancer) 

 



46 

 

Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers 

may therefore result in subtherapeutic plasma exposure to darunavir. Darunavir boosted with 

cobicistat is more sensitive to CYP3A induction than ritonavir-boosted darunavir: co-administration of 

darunavir/cobicistat with medicinal products that are strong inducers of CYP3A (e.g. St John's wort, 

rifampicin, carbamazepine, phenobarbital, and phenytoin) is contraindicated (see section 4.3). 

Co-administration of darunavir/cobicistat with weak to moderate CYP3A inducers (e.g. efavirenz, 

etravirine, nevirapine, boceprevir, fluticasone, and bosentan) is not recommended (see interaction table 

below).  

 

For co-administration with strong CYP3A4 inhibitors, the same recommendations apply independent 

of whether darunavir is boosted with ritonavir or with cobicistat (see section above).  

 

Medicinal products that may be affected by darunavir boosted with ritonavir 

 

Darunavir and ritonavir are inhibitors of CYP3A, CYP2D6 and P-gp. Co-administration of 

darunavir/ritonavir with medicinal products primarily metabolised by CYP3A and/or CYP2D6 or 

transported by P-gp may result in increased systemic exposure to such medicinal products, which 

could increase or prolong their therapeutic effect and adverse reactions.  

 

Darunavir co-administered with low dose ritonavir must not be combined with medicinal products that 

are highly dependent on CYP3A for clearance and for which increased systemic exposure is associated 

with serious and/or life-threatening events (narrow therapeutic index) (see section 4.3).  

 

The overall pharmacokinetic enhancement effect by ritonavir was an approximate 14-fold increase in 

the systemic exposure of darunavir when a single dose of 600 mg darunavir was given orally in 

combination with ritonavir at 100 mg twice daily. Therefore, darunavir must only be used in 

combination with a pharmacokinetic enhancer (see sections 4.4 and 5.2).  

 

A clinical study utilising a cocktail of medicinal products that are metabolised by cytochromes 

CYP2C9, CYP2C19 and CYP2D6 demonstrated an increase in CYP2C9 and CYP2C19 activity and 

inhibition of CYP2D6 activity in the presence of darunavir/ritonavir, which may be attributed to the 

presence of low dose ritonavir. Co-administration of darunavir and ritonavir with medicinal products 

which are primarily metabolised by CYP2D6 (such as flecainide, propafenone, metoprolol) may result 

in increased plasma concentrations of these medicinal products, which could increase or prolong their 

therapeutic effect and adverse reactions. Co-administration of darunavir and ritonavir and medicinal 

products primarily metabolised by CYP2C9 (such as warfarin) and CYP2C19 (such as methadone) 

may result in decreased systemic exposure to such medicinal products, which could decrease or 

shorten their therapeutic effect.  

 

Although the effect on CYP2C8 has only been studied in vitro, co-administration of darunavir and 

ritonavir and medicinal products primarily metabolised by CYP2C8 (such as paclitaxel, rosiglitazone, 

repaglinide) may result in decreased systemic exposure to such medicinal products, which could 

decrease or shorten their therapeutic effect.  

 

Ritonavir inhibits the transporters P-glycoprotein, OATP1B1 and OATP1B3, and co-administration 

with substrates of these transporters can result in increased plasma concentrations of these compounds 

(e.g. dabigatran etexilate, digoxin, statins and bosentan; see the Interaction table below).  

 

Medicinal products that may be affected by darunavir boosted with cobicistat 

The recommendations for darunavir boosted with ritonavir are adequate also for darunavir boosted 

with cobicistat with regard to substrates of CYP3A4, CYP2D6, P-glycoprotein, OATP1B1 and 

OATP1B3 (see contraindications and recommendations presented in the section above). Cobicistat 

150 mg given with darunavir 800 mg once daily enhances darunavir pharmacokinetic parameters in a 

comparable way to ritonavir (see section 5.2).  

 



47 

 

Unlike ritonavir, cobicistat does not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or 

UGT1A1. For further information on cobicistat, consult the cobicistat Summary of Product 

Characteristics.  

 

Interaction table 

 

Interaction studies have only been performed in adults.  

 

Several of the interaction studies (indicated by # in the table below) have been performed at lower than 

recommended doses of darunavir or with a different dosing regimen (see section 4.2 Posology). The 

effects on co-administered medicinal products may thus be underestimated and clinical monitoring of 

safety may be indicated.  

 

The interaction profile of darunavir depends on whether ritonavir or cobicistat is used as 

pharmacokinetic enhancer. Darunavir may therefore have different recommendations for concomitant 

medications depending on whether the compound is boosted with ritonavir or cobicistat. No 

interaction studies presented in the table have been performed with darunavir boosted with cobicistat. 

The same recommendations apply, unless specifically indicated. For further information on cobicistat, 

consult the cobicistat Summary of Product Characteristics.  

 

Interactions between darunavir/ritonavir and antiretroviral and non-antiretroviral medicinal products 

are listed in the table below. The direction of the arrow for each pharmacokinetic parameter is based 

on the 90% confidence interval of the geometric mean ratio being within (↔), below (↓) or above (↑) 

the 80-125% range (not determined as “ND”).  

 

In the table below the specific pharmacokinetic enhancer is specified when recommendations differ. 

When the recommendation is the same for darunavir when co-administered with a low dose ritonavir 

or cobicistat, the term “boosted darunavir” is used.  

 

The below list of examples of drug drug interactions is not comprehensive and therefore the label of 

each drug that is co-administered with darunavir should be consulted for information related to the 

route of metabolism, interaction pathways, potential risks, and specific actions to be taken with 

regards to co-administration. 

 

INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL PRODUCTS 

Medicinal products by 

therapeutic areas 

Interaction  

Geometric mean change (%) 

Recommendations concerning co-

administration 

HIV ANTIRETROVIRALS 

Integrase strand transfer inhibitors 

Dolutegravir  dolutegravir AUC ↓ 22%  

dolutegravir C24h ↓38%  

dolutegravir Cmax ↓ 11%  

darunavir ↔*  

* Using cross-study comparisons to 

historical pharmacokinetic data  

Boosted darunavir and dolutegravir can 

be used without dose adjustment.  

   

Raltegravir  Some clinical studies suggest 

raltegravir may cause a modest 

decrease in darunavir plasma 

concentrations.  

At present the effect of raltegravir on 

darunavir plasma concentrations does 

not appear to be clinically relevant. 

Boosted darunavir and raltegravir can 

be used without dose adjustments.  

Nucleo(s/t)ide reverse transcriptase inhibitors (NRTIs) 

Didanosine  

400 mg once daily  

didanosine AUC ↓ 9%  

didanosine Cmin ND  

didanosine Cmax ↓ 16%  

darunavir AUC ↔  

Boosted darunavir and didanosine can 

be used without dose adjustments.  

Didanosine is to be administered on an 

empty stomach, thus it should be 



48 

 

darunavir Cmin ↔  

darunavir Cmax ↔ 

administered 1 hour before or 2 hours 

after boosted darunavir given with 

food.  

Tenofovir disoproxil  

245 mg once daily‡  

tenofovir AUC ↑ 22%  

tenofovir Cmin ↑ 37%  

tenofovir Cmax ↑ 24%  
#darunavir AUC ↑ 21%  
#darunavir Cmin ↑ 24%  
#darunavir Cmax ↑ 16%  

(↑ tenofovir from effect on MDR-1 

transport in the renal tubules)  

Monitoring of renal function may be 

indicated when boosted darunavir is 

given in combination with tenofovir 

disoproxil, particularly in patients with 

underlying systemic or renal disease, or 

in patients taking nephrotoxic agents.  

 

Darunavir co-administered with 

cobicistat lowers the creatinine 

clearance. Refer to section 4.4 if 

creatinine clearance is used for dose 

adjustment of tenofovir disoproxil.  

Emtricitabine/tenofovir 

alafenamide  

Tenofovir alafenamide ↔ 

Tenofovir ↑ 

The recommended dose of 

emtricitabine/tenofovir alafenamide is 

200/10 mg once daily when used with 

boosted darunavir.  

Abacavir  

Emtricitabine  

Lamivudine  

Stavudine  

Zidovudine  

Not studied. Based on the different 

elimination pathways of the other 

NRTIs zidovudine, emtricitabine, 

stavudine, lamivudine, that are 

primarily renally excreted, and 

abacavir for which metabolism is 

not mediated by CYP450, no 

interactions are expected for these 

medicinal compounds and boosted 

darunavir.  

Boosted darunavir can be used with 

these NRTIs without dose adjustment.  

 

Darunavir co-administered with 

cobicistat lowers the creatinine 

clearance. Refer to section 4.4 if 

creatinine clearance is used for dose 

adjustment of emtricitabine or 

lamivudine.  

Non-nucleo(s/t)ide reverse transcriptase inhibitors (NNRTIs) 

Efavirenz  

600 mg once daily  

efavirenz AUC ↑ 21%  

efavirenz Cmin ↑ 17%  

efavirenz Cmax ↑ 15%  
#darunavir AUC ↓ 13%  
#darunavir Cmin ↓ 31%  
#darunavir Cmax ↓ 15%  

(↑ efavirenz from CYP3A 

inhibition)  

(↓ darunavir from CYP3A 

induction)  

Clinical monitoring for central nervous 

system toxicity associated with 

increased exposure to efavirenz may be 

indicated when darunavir co-

administered with low dose ritonavir is 

given in combination with efavirenz.  

 

Efavirenz in combination with 

darunavir/ritonavir 800/100 mg once 

daily may result in sub-optimal 

darunavir Cmin. If efavirenz is to be 

used in combination with 

darunavir/ritonavir, the 

darunavir/ritonavir 600/100 mg twice 

daily regimen should be used (see 

section 4.4).  

 

Co-administration with darunavir co-

administered with cobicistat is not 

recommended (see section 4.4).  

Etravirine  

100 mg twice daily  

etravirine AUC ↓ 37%  

etravirine Cmin ↓ 49%  

etravirine Cmax ↓ 32%  

darunavir AUC ↑ 15%  

darunavir Cmin ↔  

darunavir Cmax ↔ 

Darunavir co-administered with low 

dose ritonavir and etravirine 200 mg 

twice daily can be used without dose 

adjustments.  

 

Co-administration with darunavir co-

administered with cobicistat is not 

recommended (see section 4.4).  



49 

 

Nevirapine  

200 mg twice daily  

nevirapine AUC ↑ 27%  

nevirapine Cmin ↑ 47%  

nevirapine Cmax ↑ 18%  
#darunavir: concentrations were 

consistent with historical data  

(↑ nevirapine from CYP3A 

inhibition)  

Darunavir co-administered with low 

dose ritonavir and nevirapine can be 

used without dose adjustments.  

 

Co-administration with darunavir co-

administered with cobicistat is not 

recommended (see section 4.4).  

Rilpivirine  

150 mg once daily  

rilpivirine AUC ↑ 130%  

rilpivirine Cmin ↑ 178%  

rilpivirine Cmax ↑ 79%  

darunavir AUC ↔  

darunavir Cmin ↓ 11%  

darunavir Cmax ↔ 

Boosted darunavir and rilpivirine can 

be used without dose adjustments.  

HIV Protease inhibitors (PIs) - without additional co-administration of low dose ritonavir† 

Atazanavir  

300 mg once daily  

atazanavir AUC ↔  

atazanavir Cmin ↑ 52%  

atazanavir Cmax ↓ 11%  
#darunavir AUC ↔  
#darunavir Cmin ↔  
#darunavir Cmax ↔  

 

Atazanavir: comparison of 

atazanavir/ritonavir 300/100 mg 

once daily vs. atazanavir 300 mg 

once daily in combination with 

darunavir/ritonavir 400/100 mg 

twice daily.  

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg 

twice daily vs. darunavir/ritonavir 

400/100 mg twice daily in 

combination with atazanavir 300 mg 

once daily.  

Darunavir co-administered with low 

dose ritonavir and atazanavir can be 

used without dose adjustments.  

 

Darunavir co-administered with 

cobicistat should not be used in 

combination with another antiretroviral 

agent that requires 

pharmacoenhancement by means of co-

administration with an inhibitor of 

CYP3A4 (see section 4.5).  

Indinavir  

800 mg twice daily  

indinavir AUC ↑ 23%  

indinavir Cmin ↑ 125%  

indinavir Cmax ↔  
#darunavir AUC ↑ 24%  
#darunavir Cmin ↑ 44%  
#darunavir Cmax ↑ 11%  

 

Indinavir: comparison of 

indinavir/ritonavir 800/100 mg twice 

daily vs. 

indinavir/darunavir/ritonavir 

800/400/100 mg twice daily.  

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg 

twice daily vs. darunavir/ritonavir 

400/100 mg in combination with 

indinavir 800 mg twice daily.  

When used in combination with 

darunavir co-administered with low 

dose ritonavir, dose adjustment of 

indinavir from 800 mg twice daily to 

600 mg twice daily may be warranted 

in case of intolerance.  

 

Darunavir co-administered with 

cobicistat should not be used in 

combination with another antiretroviral 

agent that requires 

pharmacoenhancement by means of co-

administration with an inhibitor of 

CYP3A4 (see section 4.5).  

Saquinavir  

1,000 mg twice daily  

#darunavir AUC ↓ 26%  
#darunavir Cmin ↓ 42%  
#darunavir Cmax ↓ 17%  

saquinavir AUC ↓ 6%  

saquinavir Cmin ↓ 18%  

saquinavir Cmax ↓ 6%  

 

Saquinavir: comparison of 

saquinavir/ritonavir 1,000/100 mg 

twice daily vs. 

It is not recommended to combine 

darunavir co-administered with low 

dose ritonavir with saquinavir.  

 

Darunavir co-administered with 

cobicistat should not be used in 

combination with another antiretroviral 

agent that requires 

pharmacoenhancement by means of co-



50 

 

saquinavir/darunavir/ritonavir 

1,000/400/100 mg twice daily  

Darunavir: comparison of 

darunavir/ritonavir 400/100 mg 

twice daily vs. darunavir/ritonavir 

400/100 mg in combination with 

saquinavir 1,000 mg twice daily.  

administration with an inhibitor of 

CYP3A4 (see section 4.5).  

HIV Protease inhibitors (PIs) - with co-administration of low dose ritonavir† 

Lopinavir/ritonavir  

400/100 mg twice daily  

   

   

   

 

Lopinavir/ritonavir  

533/133.3 mg twice daily  

lopinavir AUC ↑ 9%  

lopinavir Cmin ↑ 23%  

lopinavir Cmax ↓ 2%  

darunavir AUC ↓ 38%‡  

darunavir Cmin ↓ 51%‡  

darunavir Cmax ↓ 21%‡  

lopinavir AUC ↔  

lopinavir Cmin ↑ 13%  

lopinavir Cmax ↑ 11%  

darunavir AUC ↓ 41%  

darunavir Cmin ↓ 55%  

darunavir Cmax ↓ 21%  
‡ based upon non dose normalised 

values  

Due to a decrease in the exposure 

(AUC) of darunavir by 40%, 

appropriate doses of the combination 

have not been established. Hence, 

concomitant use of boosted darunavir 

and the combination product 

lopinavir/ritonavir is contraindicated 

(see section 4.3).  

CCR5 ANTAGONIST 

Maraviroc  

150 mg twice daily  

maraviroc AUC ↑ 305%  

maraviroc Cmin ND  

maraviroc Cmax ↑ 129%  

darunavir, ritonavir concentrations 

were consistent with historical data  

The maraviroc dose should be 150 mg 

twice daily when co-administered with 

boosted darunavir.  

α1-ADRENORECEPTOR ANTAGONIST 

Alfuzosin Based on theoretical considerations 

darunavir is expected to increase 

alfuzosin plasma concentrations. 

(CYP3A inhibition) 

Co-administration of boosted darunavir 

and alfuzosin is contraindicated (see 

section 4.3). 

ANAESTHETIC 

Alfentanil  Not studied. The metabolism of 

alfentanil is mediated via CYP3A, 

and may as such be inhibited by 

boosted darunavir.  

The concomitant use with boosted 

darunavir may require to lower the dose 

of alfentanil and requires monitoring 

for risks of prolonged or delayed 

respiratory depression.  

ANTIANGINA/ANTIARRHYTHMIC 

Disopyramide  

Flecainide  

Lidocaine (systemic) 

Mexiletine  

Propafenone  

 

Amiodarone  

Bepridil  

Dronedarone  

Ivabradine 

Quinidine  

Ranolazine  

Not studied. Boosted darunavir is 

expected to increase these 

antiarrhythmic plasma 

concentrations.  

(CYP3A and/or CYP2D6 inhibition)  

Caution is warranted and ther 

apeutic concentration monitoring, if 

available, is recommended for these 

antiarrhythmics when co-administered 

with boosted darunavir.  

 

Co-administration of boosted darunavir 

and amiodarone, bepridil, dronedarone, 

ivabradine, quinidine, or ranolazine is 

contraindicated (see section 4.3).   

Digoxin  

0.4 mg single dose  

digoxin AUC ↑ 61%  

digoxin Cmin ND  

digoxin Cmax ↑ 29%  

(↑ digoxin from probable inhibition 

of P-gp)  

Given that digoxin has a narrow 

therapeutic index, it is recommended 

that the lowest possible dose of digoxin 

should initially be prescribed in case 

digoxin is given to patients on boosted 

darunavir therapy. The digoxin dose 



51 

 

should be carefully titrated to obtain the 

desired clinical effect while assessing 

the overall clinical state of the subject.  

ANTIBIOTIC 

Clarithromycin  

500 mg twice daily  

clarithromycin AUC ↑ 57%  

clarithromycin Cmin ↑ 174%  

clarithromycin Cmax ↑ 26%  
#darunavir AUC ↓ 13%  
#darunavir Cmin ↑ 1%  
#darunavir Cmax ↓ 17%  

14-OH-clarithromycin 

concentrations were not detectable 

when combined with 

darunavir/ritonavir.  

(↑ clarithromycin from CYP3A 

inhibition and possible P-gp 

inhibition)  

Caution should be exercised when 

clarithromycin is combined with 

boosted darunavir.  

 

For patients with renal impairment the 

Summary of Product Characteristics for 

clarithromycin should be consulted for 

the recommended dose.  

ANTICOAGULANT/PLATELET AGGREGATION INHIBITOR 

Apixaban  

Edoxaban  

Rivaroxaban  

Not studied. Co-administration of 

boosted daruanvir with these 

anticoagulants may increase 

concentrations of the anticoagulant, 

which may lead to an increased 

bleeding risk.  

(CYP3A and/or P-gp inhibition)  

The use of boosted darunavir and these 

anticoagulants is not recommended.  

Dabigatran 

Ticagrelor 

Not studied. Co-administration with 

boosted darunavir may lead to a 

substantial increase in exposure to 

dabigatran or ticagrelor. 

Concomitant administration of 

boosted darunavir with 

dabigatran or ticagrelor is 

contraindicated (see section 4.3). 

 

Use of other antiplatelets not 

affected by CYP inhibition or 

induction (e.g. prasugrel) is 

recommended. 

Warfarin  Not studied. Warfarin concentrations 

may be affected when co-

administered with boosted 

darunavir.  

It is recommended that the international 

normalised ratio (INR) be monitored 

when warfarin is combined with 

boosted darunavir.  

ANTICONVULSANTS 

Phenobarbital  

Phenytoin  

Not studied. Phenobarbital and 

phenytoin are expected to decrease 

plasma concentrations of darunavir 

and its pharmacoenhancer.  

(induction of CYP450 enzymes)  

Darunavir co-administered with low 

dose ritonavir should not be used in 

combination with these medicines.  

 

The use of these medicines with 

darunavir/cobicistat is contraindicated 

(see section 4.3).  

Carbamazepine  

200 mg twice daily  

carbamazepine AUC ↑ 45%  

carbamazepine Cmin ↑ 54%  

carbamazepine Cmax ↑ 43%  

darunavir AUC ↔  

darunavir Cmin ↓ 15%  

darunavir Cmax ↔ 

No dose adjustment for 

darunavir/ritonavir is recommended. If 

there is a need to combine 

darunavir/ritonavir and carbamazepine, 

patients should be monitored for 

potential carbamazepine-related 

adverse events. Carbamazepine 

concentrations should be monitored and 

its dose should be titrated for adequate 

response. Based upon the findings, the 

carbamazepine dose may need to be 



52 

 

reduced by 25% to 50% in the presence 

of darunavir/ritonavir.  

 

The use of carbamazepine with 

darunavir co-administered with 

cobicistat is contraindicated (see 

section 4.3).  

Clonazepam Not studied. Co administration of 

boosted darunavir with clonazepam 

may increase concentrations of 

clonazepam. (CYP3A inhibition) 

Clinical monitoring is recommended 

when co administering boosted 

darunavir and clonazepam. 

ANTIDEPRESSANTS 

Paroxetine  

20 mg once daily  

   

   

   

Sertraline  

50 mg once daily  

   

   

   

   

   

 

 

 

 

 

 

 

   

Amitriptyline  

Desipramine  

Imipramine  

Nortriptyline  

Trazodone  

paroxetine AUC ↓ 39%  

paroxetine Cmin ↓ 37%  

paroxetine Cmax ↓ 36%  
#darunavir AUC ↔  
#darunavir Cmin ↔  
#darunavir Cmax ↔  

sertraline AUC ↓ 49%  

sertraline Cmin ↓ 49%  

sertraline Cmax ↓ 44%  
#darunavir AUC ↔  
#darunavir Cmin ↓ 6%  
#darunavir Cmax ↔  

 

In contrast to these data with 

darunavir/ritonavir, 

darunavir/cobicistat may increase 

these antidepressant plasma 

concentrations (CYP2D6 and/or 

CYP3A inhibition). 

  

Concomitant use of boosted 

darunavir and these antidepressants 

may increase concentrations of the 

antidepressant.  

(CYP2D6 and/or CYP3A inhibition)  

If antidepressants are co-administered 

with boosted darunavir, the 

recommended approach is a dose 

titration of the antidepressant based on 

a clinical assessment of antidepressant 

response. In addition, patients on a 

stable dose of these antidepressants 

who start treatment with boosted 

darunavir should be monitored for 

antidepressant response.  

   

   

   

   

   

   

   

   

 

Clinical monitoring is recommended 

when co-administering boosted 

darunavir with these antidepressants 

and a dose adjustment of the 

antidepressant may be needed.  

ANTI-DIABETICS 

Metformin  Not studied. Based on theoretical 

considerations darunavir co-

administered with cobicistat is 

expected to increase metformin 

plasma concentrations.  

(MATE1 inhibition)  

Careful patient monitoring and dose 

adjustment of metformin is 

recommended in patients who are 

taking darunavir co-administered with 

cobicistat.  

(not applicable for darunavir co-

administered with ritonavir)  

ANTIEMETICS 

Domperidone Not studied. Co-administration of domperidone 

with boosted darunavir is 

contraindicated. 

ANTIFUNGALS 

Voriconazole  Not studied. Ritonavir may decrease 

plasma concentrations of 

voriconazole.  

(induction of CYP450 enzymes)  

 

Concentrations of voriconazole may 

increase or decrease when co-

administered with darunavir co-

administered with cobicistat.  

Voriconazole should not be combined 

with boosted darunavir unless an 

assessment of the benefit/risk ratio 

justifies the use of voriconazole.  



53 

 

(inhibition of CYP450 enzymes)  

Fluconazole  

Isavuconazole 

Itraconazole 

Posaconazole  

 

 

 

 

 

Clotrimazole   

Not studied. Boosted darunavir may 

increase antifungal plasma 

concentrations and posaconazole, 

isavuconazole, itraconazole  or 

fluconazole may increase darunavir 

concentrations.  

(CYP3A  and/or P-gp inhibition)  

 

Not studied. Concomitant systemic 

use of clotrimazole and boosted 

darunavir may increase plasma 

concentrations of darunavir and/or 

clotrimazole. 

Darunavir AUC24h ↑ 33% (based on 

population pharmacokinetic model) 

Caution is warranted and clinical 

monitoring is recommended. 

When co-administration is required the 

daily dose of itraconazole should not 

exceed 200 mg. 

ANTIGOUT MEDICINES 

Colchicine  Not studied. Concomitant use of 

colchicine and boosted darunavir 

may increase the exposure to 

colchicine.  

(CYP3A and/ or P-gp inhibition)  

A reduction in colchicine dosage or an 

interruption of colchicine treatment is 

recommended in patients with normal 

renal or hepatic function if treatment 

with boosted darunavir is required. For 

patients with renal or hepatic 

impairment colchicine with boosted 

darunavir is contraindicated (see 

sections 4.3 and 4.4).  

ANTIMALARIALS 

Artemether/Lumefantrine  

80/480 mg, 6 doses at 0, 8, 

24, 36, 48, and 60 hours  

artemether AUC ↓ 16%  

artemether Cmin ↔  

artemether Cmax ↓ 18%  

dihydroartemisinin AUC ↓ 18%  

dihydroartemisinin Cmin ↔  

dihydroartemisinin Cmax ↓ 18%  

lumefantrine AUC ↑ 175%  

lumefantrine Cmin ↑ 126%  

lumefantrine Cmax ↑ 65%  

darunavir AUC ↔  

darunavir Cmin ↓ 13%  

darunavir Cmax ↔ 

The combination of boosted darunavir 

and artemether/lumefantrine can be 

used without dose adjustments; 

however, due to the increase in 

lumefantrine exposure, the combination 

should be used with caution.  

ANTIMYCOBACTERIALS 

Rifampicin  

Rifapentine  

Not studied. Rifapentine and 

rifampicin are strong CYP3A 

inducers and have been shown to 

cause profound decreases in 

concentrations of other protease 

inhibitors, which can result in 

virological failure and resistance 

development (CYP450 enzyme 

induction). During attempts to 

overcome the decreased exposure by 

increasing the dose of other protease 

inhibitors with low dose ritonavir, a 

high frequency of liver reactions 

was seen with rifampicin.  

The combination of rifapentine and 

boosted darunavir is not recommended.  

 

The combination of rifampicin and 

boosted darunavir is contraindicated 

(see section 4.3).  

Rifabutin  

150 mg once every other day  

rifabutin AUC** ↑ 55%  

rifabutin Cmin** ↑ ND  

rifabutin Cmax** ↔  

darunavir AUC ↑ 53%  

darunavir Cmin ↑ 68%  

A dosage reduction of rifabutin by 75% 

of the usual dose of 300 mg/day (i.e. 

rifabutin 150 mg once every other day) 

and increased monitoring for rifabutin 

related adverse events is warranted in 



54 

 

darunavir Cmax ↑ 39%  

** sum of active moieties of 

rifabutin (parent drug + 

25-O-desacetyl metabolite)  

 

The interaction trial showed a 

comparable daily systemic exposure 

for rifabutin between treatment at 

300 mg once daily alone and 150 mg 

once every other day in combination 

with darunavir/ritonavir 

(600/100 mg twice daily) with an 

about 10-fold increase in the daily 

exposure to the active metabolite 25-

O-desacetylrifabutin. Furthermore, 

AUC of the sum of active moieties 

of rifabutin (parent drug + 25-O- 

desacetyl metabolite) was increased 

1.6-fold, while Cmax remained 

comparable.  

Data on comparison with a 150 mg 

once daily reference dose is lacking.  

 

(Rifabutin is an inducer and 

substrate of CYP3A.) An increase of 

systemic exposure to darunavir was 

observed when darunavir co-

administered with 100 mg ritonavir 

was co-administered with rifabutin 

(150 mg once every other day).  

patients receiving the combination with 

darunavir co-administered with 

ritonavir. In case of safety issues, a 

further increase of the dosing interval 

for rifabutin and/or monitoring of 

rifabutin levels should be considered.  

Consideration should be given to 

official guidance on the appropriate 

treatment of tuberculosis in HIV 

infected patients.  

Based upon the safety profile of 

darunavir/ritonavir, the increase in 

darunavir exposure in the presence of 

rifabutin does not warrant a dose 

adjustment for darunavir/ritonavir.  

Based on pharmacokinetic modeling, 

this dosage reduction of 75% is also 

applicable if patients receive rifabutin 

at doses other than 300 mg/day.  

 

Co-administration of darunavir co-

administered with cobicistat and 

rifabutin is not recommended.  

ANTINEOPLASTICS 

Dasatinib  

Nilotinib  

Vinblastine  

Vincristine  

     

 

 

 

 

 

Everolimus 

Irinotecan 

Not studied. Boosted darunavir is 

expected to increase these 

antineoplastic plasma 

concentrations.  

(CYP3A inhibition)  

Concentrations of these medicinal 

products may be increased when co-

administered with boosted darunavir 

resulting in the potential for increased 

adverse events usually associated with 

these agents.  

Caution should be exercised when 

combining one of these antineoplastic 

agents with boosted darunavir.  

 

Concominant use of everolimus or  

Irinotecan and boosted darunavir is not 

recommended.  

ANTIPSYCHOTICS/NEUROLEPTICS  

Quetiapine  Not studied. Boosted darunavir is 

expected to increase these 

antipsychotic plasma concentrations.  

(CYP3A inhibition)  

Concomitant administration of boosted 

darunavir and quetiapine is 

contraindicated as it may increase 

quetiapine-related toxicity. Increased 

concentrations of quetiapine may lead 

to coma (see section 4.3).  

Perphenazine  

Risperidone  

Thioridazine  

 

Lurasidone 

Pimozide  

Sertindole  

Not studied. Boosted darunavir is 

expected to increase these 

antipsychotic plasma concentrations.  

(CYP3A, CYP2D6 and/or P-gp 

inhibition)  

A dose decrease may be needed for 

these drugs when co-administered with 

boosted darunavir.  

 

Concominant administration of boosted 

darunavir and lurasidone, pimozide or 

sertindole is contraindicated (see 

section 4.3).  

β-BLOCKERS 



55 

 

Carvedilol 

Metoprolol 

Timolol 

Not studied. Boosted darunavir is 

expected to increase these β-blocker 

plasma concentrations.  

(CYP2D6 inhibition)  

Clinical monitoring is recommended 

when co-administering boosted 

darunavir with β-blockers. A lower 

dose of the β-blocker should be 

considered.  

CALCIUM CHANNEL BLOCKERS 

Amlodipine  

Diltiazem  

Felodipine  

Nicardipine  

Nifedipine  

Verapamil  

Not studied. Boosted darunavir can 

be expected to increase the plasma 

concentrations of calcium channel 

blockers.  

(CYP3A and/or CYP2D6 inhibition)  

Clinical monitoring of therapeutic and 

adverse effects is recommended when 

these medicines are concomitantly 

administered with boosted darunavir.  

CORTICOSTEROIDS 

Corticosteroids primarily 

metabolised by CYP3A 

(including betamethasone, 

budesonide, fluticasone, 

mometasone, prednisone, 

triamcinolone) 

Fluticasone: in a clinical study 

where ritonavir 100 mg capsules 

twice daily were co-administered 

with 50 μg intranasal fluticasone 

propionate (4 times daily) for 7 days 

in healthy subjects, fluticasone 

propionate plasma concentrations 

increased significantly, whereas the 

intrinsic cortisol levels decreased by 

approximately 86% (90% CI 82-

89%). Greater effects may be 

expected when fluticasone 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. The effects of high 

fluticasone systemic exposure on 

ritonavir plasma levels are unknown.  

 

Other corticosteroids: interaction not 

studied. Plasma concentrations of 

these medicinal products may be 

increased when co-administered 

with boosted darunavir, resulting in 

reduced serum cortisol 

concentrations. 

Concomitant use of boosted darunavir 

and corticosteroids that are metabolised 

by CYP3A (e.g. fluticasone propionate 

or other inhaled or nasal 

corticosteroids) may increase the risk of 

development of systemic corticosteroid 

effects, including Cushing’s syndrome 

and adrenal suppression.  

Co-administration with CYP3A-

metabolised corticosteroids is not 

recommended unless the potential 

benefit to the patient outweighs the risk, 

in which case patients should be 

monitored for systemic corticosteroid 

effects. 

Alternative corticosteroids which are 

less dependent on CYP3A metabolism 

e.g. beclomethasone for intranasal or 

inhalational use should be considered, 

particularly for long term use.  

Dexamethasone (systemic)  Not studied. Dexamethasone may 

decrease plasma concentrations of 

darunavir.  

(CYP3A induction)  

Systemic dexamethasone should be 

used with caution when combined with 

boosted darunavir.  

ENDOTHELIN RECEPTOR ANTAGONISTS 

Bosentan  Not studied. Concomitant use of 

bosentan and boosted darunavir may 

increase plasma concentrations of 

bosentan.  

Bosentan is expected to decrease 

plasma concentrations of darunavir 

and/or its pharmacoenhancer.  

(CYP3A induction)  

When administered concomitantly with 

darunavir and low dose ritonavir, the 

patient's tolerability of bosentan should 

be monitored.  

 

Co administration of darunavir co-

administered with cobicistat and 

bosentan is not recommended.  

HEPATITIS C VIRUS (HCV) DIRECT-ACTING ANTIVIRALS 

NS3-4A protease inhibitors 



56 

 

Elbasvir/grazoprevir Boosted darunavir may increase the 

exposure to grazoprevir. 

(CYP3A and OATP1B inhibition). 

Concomitant use of boosted darunavir 

and elbasvir/grazoprevir is 

contraindicated (see section 4.3). 

Boceprevir  

800 mg three times daily  

boceprevir AUC ↓ 32%  

boceprevir Cmin ↓ 35%  

boceprevir Cmax ↓ 25%  

darunavir AUC ↓ 44%  

darunavir Cmin ↓ 59%  

darunavir Cmax ↓ 36%  

It is not recommended to co-administer 

boosted darunavir and boceprevir.  

Glecaprevir/pibrentasvir Based on theoretical considerations 

boosted darunavir may increase the 

exposure to glecaprevir and 

pibrentasvir. 

(P-gp, BCRP and/or OATP1B1/3 

inhibition) 

It is not recommended to 

co-administer boosted darunavir with 

glecaprevir/pibrentasvir. 

Simeprevir  simeprevir AUC ↑ 159%  

simeprevir Cmin ↑ 358%  

simeprevir Cmax ↑ 79%  

darunavir AUC ↑ 18%  

darunavir Cmin ↑ 31%  

darunavir Cmax ↔  

 

The dose of simeprevir in this 

interaction study was 50 mg when 

co-administered in combination with 

darunavir/ritonavir, compared to 

150 mg in the simeprevir alone 

treatment group.  

It is not recommended to co-administer 

boosted darunavir and simeprevir.  

HERBAL PRODUCTS 

St John's wort 

(Hypericum perforatum) 

Not studied. St John's wort is 

expected to decrease the plasma 

concentrations of darunavir or its 

pharmacoenhancers.  

(CYP450 induction)  

Boosted darunavir must not be used 

concomitantly with products containing 

St John's wort (Hypericum perforatum) 

(see section 4.3). If a patient is already 

taking St John's wort, stop St John's 

wort and if possible check viral levels. 

Darunavir exposure (and also ritonavir 

exposure) may increase on stopping St 

John's wort. The inducing effect may 

persist for at least 2 weeks after 

cessation of treatment with St John's 

wort.  

HMG CO-A REDUCTASE INHIBITORS 

Lovastatin  

Simvastatin  

Not studied. Lovastatin and 

simvastatin are expected to have 

markedly increased plasma 

concentrations when co-

administered with boosted 

darunavir.  

(CYP3A inhibition)  

Increased plasma concentrations of 

lovastatin or simvastatin may cause 

myopathy, including rhabdomyolysis. 

Concomitant use of boosted darunavir 

with lovastatin and simvastatin is 

therefore contraindicated (see section 

4.3).  

Atorvastatin  

10 mg once daily  

atorvastatin AUC ↑ 3-4 fold  

atorvastatin Cmin ↑ ≈5.5-10 fold  

atorvastatin Cmax ↑ ≈2 fold  
#darunavir/ritonavir 

 

atorvastatin AUC ↑ 290% Ω 

atorvastatin Cmax ↑ 319% Ω 

atorvastatin Cmin ND Ω 
Ω with darunavir/cobicistat 800/150 mg 

  

When administration of atorvastatin 

and boosted darunavir is desired, it is 

recommended to start with an 

atorvastatin dose of 10 mg once daily. 

A gradual dose increase of atorvastatin 

may be tailored to the clinical response.  



57 

 

Pravastatin  

40 mg single dose  

pravastatin AUC ↑ 81%¶  

pravastatin Cmin ND  

pravastatin Cmax ↑ 63%  
¶ an up to five-fold increase was 

seen in a limited subset of subjects  

When administration of pravastatin and 

boosted darunavir is required, it is 

recommended to start with the lowest 

possible dose of pravastatin and titrate 

up to the desired clinical effect while 

monitoring for safety.  

Rosuvastatin  

10 mg once daily  

rosuvastatin AUC ↑ 48%║  

rosuvastatin Cmax ↑ 144%║  
║ based on published data with 
darunavir/ritonavir  
 

rosuvastatin AUC ↑ 93%§ 

rosuvastatin Cmax ↑ 277%§ 

rosuvastatin Cmin ND§ 
§ with darunavir/cobicistat 800/150 mg  

When administration of rosuvastatin 

and boosted darunavir is required, it is 

recommended to start with the lowest 

possible dose of rosuvastatin and titrate 

up to the desired clinical effect while 

monitoring for safety.  

OTHER LIPID MODIFYING AGENTS 

Lomitapide Based on theoretical considerations 

boosted darunavir is expected to 

increase the exposure of lomitapide 

when co-administered.  

(CYP3A inhibition) 

Co-administration is contraindicated 

(see section 4.3) 

H2-RECEPTOR ANTAGONISTS 

Ranitidine  

150 mg twice daily  

#darunavir AUC ↔  
#darunavir Cmin ↔  
#darunavir Cmax ↔ 

Boosted darunavir can be co-

administered with H2-receptor 

antagonists without dose adjustments.  

IMMUNOSUPPRESSANTS 

Ciclosporin  

Sirolimus  

Tacrolimus  

Everolimus  

Not studied. Exposure to these 

immunosuppressants will be 

increased when co-administered 

with boosted darunavir.  

(CYP3A inhibition)  

Therapeutic drug monitoring of the 

immunosuppressive agent must be done 

when co-administration occurs.  

Concomitant use of everolimus and 

boosted darunavir is not recommended.  

INHALED BETA AGONISTS 

Salmeterol  Not studied. Concomitant use of 

salmeterol and boosted darunavir 

may increase plasma concentrations 

of salmeterol.  

Concomitant use of salmeterol and 

boosted darunavir is not recommended. 

The combination may result in 

increased risk of cardiovascular adverse 

event with salmeterol, including QT 

prolongation, palpitations and sinus 

tachycardia.  

NARCOTIC ANALGESICS / TREATMENT OF OPIOID DEPENDENCE 

Methadone  

individual dose ranging from 

55 mg to 150 mg once daily  

R(-) methadone AUC ↓ 16%  

R(-) methadone Cmin ↓ 15%  

R(-) methadone Cmax ↓ 24%  

 

Darunavir/cobicistat may, in 

contrast, increase methadone plasma 

concentrations (see cobicistat 

SmPC).  

No adjustment of methadone dosage is 

required when initiating co-

administration with boosted darunavir. 

However, adjustment of the methadone 

dose may be necessary when 

concomitantly administered for a longer 

period of time. Therefore, clinical 

monitoring is recommended, as 

maintenance therapy may need to be 

adjusted in some patients.  

Buprenorphine/naloxone  

8/2 mg–16/4 mg once daily  

buprenorphine AUC ↓ 11%  

buprenorphine Cmin ↔  

buprenorphine Cmax ↓ 8%  

norbuprenorphine AUC ↑ 46%  

norbuprenorphine Cmin ↑ 71%  

norbuprenorphine Cmax ↑ 36%  

naloxone AUC ↔  

naloxone Cmin ND  

The clinical relevance of the increase in 

norbuprenorphine pharmacokinetic 

parameters has not been established. 

Dose adjustment for buprenorphine 

may not be necessary when co-

administered with boosted darunavir 

but a careful clinical monitoring for 



58 

 

naloxone Cmax ↔ signs of opiate toxicity is 

recommended.  

Fentanyl 

Oxycodone 

Tramadol 

Based on theoretical considerations 

boosted darunavir may increase 

plasma concentrations of these 

analgesics. 

(CYP2D6 and/or CYP3A inhibition) 

Clinical monitoring is recommended 

when co-administering boosted 

darunavir with these analgesics. 

OESTROGEN-BASED CONTRACEPTIVES  

Drospirenone 

Ethinylestradiol 

(3 mg/0.02 mg once daily) 

 

 

 

 

Ethinylestradiol  

Norethindrone  

35 μg/1 mg once daily  

drospirenone AUC ↑ 58%€ 

drospirenone Cmin ND€ 

drospirenone Cmax ↑ 15%€ 

ethinylestradiol AUC  30%€ 

ethinylestradiol Cmin ND€ 

ethinylestradiol Cmax  14%€ 
€ with darunavir/cobicistat  

 

ethinylestradiol AUC ↓ 44%  

ethinylestradiol Cmin ↓ 62%  

ethinylestradiol Cmax ↓ 32%  

norethindrone AUC ↓ 14%  

norethindrone Cmin ↓ 30%  

norethindrone Cmax ↔ 
β with darunavir/ritonavir 

When darunavir is coadministered with 

a drospirenone-containing product, 

clinical monitoring is recommended 

due to the potential for hyperkalaemia. 

 

Alternative or additional contraceptive 

measures are recommended when 

oestrogen-based contraceptives are co-

administered with boosted darunavir. 

Patients using oestrogens as hormone 

replacement therapy should be 

clinically monitored for signs of 

oestrogen deficiency.  

OPIOID ANTAGONIST 

Naloxegol Not studied. Co-administration of boosted 

darunavir and naloxegol is 

contraindicated. 

PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS 

For the treatment of erectile 

dysfunction  

Avanafil  

Sildenafil  

Tadalafil  

Vardenafil  

In an interaction study #, a 

comparable systemic exposure to 

sildenafil was observed for a single 

intake of 100 mg sildenafil alone 

and a single intake of 25 mg 

sildenafil co-administered with 

darunavir and low dose ritonavir.  

The combination of avanafil and 

boosted darunavir is contraindicated 

(see section 4.3).  

Concomitant use of other PDE-5 

inhibitors for the treatment of erectile 

dysfunction with boosted darunavir 

should be done with caution. If 

concomitant use of boosted darunavir 

with sildenafil, vardenafil or tadalafil is 

indicated, sildenafil at a single dose not 

exceeding 25 mg in 48 hours, 

vardenafil at a single dose not 

exceeding 2.5 mg in 72 hours or 

tadalafil at a single dose not exceeding 

10 mg in 72 hours is recommended.  

For the treatment of 

pulmonary arterial 

hypertension  

Sildenafil  

Tadalafil  

Not studied. Concomitant use of 

sildenafil or tadalafil for the 

treatment of pulmonary arterial 

hypertension and boosted darunavir 

may increase plasma concentrations 

of sildenafil or tadalafil.  

(CYP3A inhibition)  

A safe and effective dose of sildenafil 

for the treatment of pulmonary arterial 

hypertension co-administered with 

boosted darunavir has not been 

established. There is an increased 

potential for sildenafil-associated 

adverse events (including visual 

disturbances, hypotension, prolonged 

erection and syncope). Therefore, co-

administration of boosted darunavir and 

sildenafil when used for the treatment 

of pulmonary arterial hypertension is 

contraindicated (see section 4.3).  

Co-administration of tadalafil for the 

treatment of pulmonary arterial 



59 

 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in 

pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, 

the animal data as well as the clinical experience in pregnant women should be taken into account.  

 

There are no adequate and well controlled studies on pregnancy outcome with darunavir in pregnant 

women. Studies in animals do not indicate direct harmful effects with respect to pregnancy, 

embryonal/foetal development, parturition or postnatal development (see section 5.3).  

 

hypertension with boosted darunavir is 

not recommended.  

PROTON PUMP INHIBITORS 

Omeprazole  

20 mg once daily  

#darunavir AUC ↔  
#darunavir Cmin ↔  
#darunavir Cmax ↔ 

Boosted darunavir can be co-

administered with proton pump 

inhibitors without dose adjustments.  

SEDATIVES/HYPNOTICS 

Buspirone  

Clorazepate  

Diazepam  

Estazolam  

Flurazepam  

Midazolam (parenteral)  

Zoldipem  

   

   

   

   

 

 

 

 

 

 

 

 

 

 

Midazolam (oral)  

Triazolam  

Not studied. Sedative/hypnotics are 

extensively metabolised by CYP3A. 

Co-administration with boosted 

darunavir may cause a large increase 

in the concentration of these 

medicines.  

   

If parenteral midazolam is co-

administered with boosted darunavir 

it may cause a large increase in the 

concentration of this 

benzodiazepine. Data from 

concomitant use of parenteral 

midazolam with other protease 

inhibitors suggest a possible 3-4 fold 

increase in midazolam plasma 

levels.  

Clinical monitoring is recommended 

when co-administering boosted 

darunavir with these 

sedatives/hypnotics and a lower dose of 

the sedatives/hypnotics should be 

considered.  

   

If parenteral midazolam is co-

administered with boosted darunavir, 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. Dose adjustment 

for midazolam should be considered, 

especially if more than a single dose of 

midazolam is administered.  

 

Boosted darunavir with triazolam or 

oral midazolam is contraindicated (see 

section 4.3)  

TREATMENT FOR PREMATURE EJACULATION 

Dapoxetine Not studied. Co-administration of boosted darunavir 

with dapoxetine is contraindicated. 

UROLOGICAL DRUGS 

Fesoterodine 

Solifenacin 

Not studied. Use with caution. Monitor for 

fesoterodine or solifenacin adverse 

reactions, dose reduction of 

fesoterodine or solifenacin may be 

necessary. 

# Studies have been performed at lower than recommended doses of darunavir or with a different dosing regimen (see 
section 4.2 Posology). 

† The efficacy and safety of the use of darunavir with 100 mg ritonavir and any other HIV PI (e.g. (fos)amprenavir, 
nelfinavir and tipranavir) has not been established in HIV patients. According to current treatment guidelines, dual therapy 

with protease inhibitors is generally not recommended.  
‡ Study was conducted with tenofovir disoproxil fumarate 300 mg once daily. 



60 

 

Treatment with darunavir/cobicistat 800/150 mg during pregnancy results in low darunavir exposure 

(see section 5.2), which may be associated with an increased risk of treatment failure and an increased 

risk of HIV transmission to the child. Therapy with Darunavir/cobicistat should not be initiated during 

pregnancy, and women who become pregnant during therapy with Darunavir/cobicistat should be 

switched to an alternative regimen (see sections 4.2 and 4.4).  

 

Darunavir co-administered with low dose ritonavir should be used during pregnancy only if the 

potential benefit justifies the potential risk.  

 

Breast-feeding 

 

It is not known whether darunavir is excreted in human milk. Studies in rats have demonstrated that 

darunavir is excreted in milk and at high levels (1,000 mg/kg/day) resulted in toxicity. Because of both 

the potential for HIV transmission and the potential for adverse reactions in breast-fed infants, mothers 

should be instructed not to breast-feed under any circumstances if they are receiving darunavir.  

 

Fertility 

 

No human data on the effect of darunavir on fertility are available. There was no effect on mating or 

fertility with darunavir treatment in rats (see section 5.3).  

 

4.7 Effects on ability to drive and use machines 

 

Darunavir in combination with cobicistat or ritonavir has no or negligible influence on the ability to 

drive and use machines. However, dizziness has been reported in some patients during treatment with 

regimens containing darunavir co-administered with cobicistat or low dose ritonavir and should be 

borne in mind when considering a patient's ability to drive or operate machinery (see section 4.8).  

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

During the clinical development program (N=2,613 treatment-experienced subjects who initiated 

therapy with darunavir/ritonavir 600/100 mg twice daily), 51.3% of subjects experienced at least one 

adverse reaction. The total mean treatment duration for subjects was 95.3 weeks. The most frequent 

adverse reactions reported in clinical trials and as spontaneous reports are diarrhoea, nausea, rash, 

headache and vomiting. The most frequent serious reactions are acute renal failure, myocardial 

infarction, immune reconstitution inflammatory syndrome, thrombocytopenia, osteonecrosis, 

diarrhoea, hepatitis and pyrexia.  

 

In the 96 week analysis, the safety profile of darunavir/ritonavir 800/100 mg once daily in treatment-

naïve subjects was similar to that seen with darunavir/ritonavir 600/100 mg twice daily in treatment-

experienced subjects except for nausea which was observed more frequently in treatment-naïve 

subjects. This was driven by mild intensity nausea. No new safety findings were identified in the 

192 week analysis of the treatment-naïve subjects in which the mean treatment duration of 

darunavir/ritonavir 800/100 mg once daily was 162.5 weeks.  

 

During the Phase III clinical trial GS-US-216-130 with darunavir/cobicistat (N=313 treatment-naïve 

and treatment-experienced subjects), 66.5% of subjects experienced at least one adverse reaction. The 

mean treatment duration was 58.4 weeks. The most frequent adverse reactions reported were diarrhoea 

(28%), nausea (23%), and rash (16%). Serious adverse reactions are diabetes mellitus, (drug) 

hypersensitivity, immune reconstitution inflammatory syndrome, rash and vomiting.  

 

For information on cobicistat, consult the cobicistat Summary of Product Characteristics.  

 

Tabulated list of adverse reactions 

 



61 

 

Adverse reactions are listed by system organ class (SOC) and frequency category. Within each 

frequency category, adverse reactions are presented in order of decreasing seriousness. Frequency 

categories are defined as follows: 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) and not known (frequency cannot be estimated 

from the available data).  

 

Adverse reactions observed with darunavir/ritonavir in clinical trials and post-marketing 

 

MedDRA system organ class  

Frequency category  

Adverse reaction  

Infections and infestations 

Uncommon  herpes simplex  

Blood and lymphatic system disorders 

Uncommon  

 

Rare  

thrombocytopenia, neutropenia, anaemia, leucopenia  

 

increased eosinophil count  

Immune system disorders 

Uncommon  immune reconstitution inflammatory syndrome, (drug) 

hypersensitivity  

Endocrine disorders 

Uncommon  hypothyroidism, increased blood thyroid stimulating 

hormone  

Metabolism and nutrition disorders 

Common  

 

 

 

 

Uncommon  

diabetes mellitus, hypertriglyceridaemia, 

hypercholesterolaemia, hyperlipidaemia  

 

gout, anorexia, decreased appetite, decreased weight, 

increased weight, hyperglycaemia, insulin resistance, 

decreased high density lipoprotein, increased appetite, 

polydipsia, increased blood lactate dehydrogenase  

Psychiatric disorders 

Common  

 

Uncommon  

 

 

Rare  

insomnia  

 

depression, disorientation, anxiety, sleep disorder, 

abnormal dreams, nightmare, decreased libido  

 

confusional state, altered mood, restlessness  

Nervous system disorders 

Common  

 

Uncommon  

 

 

 

Rare  

headache, peripheral neuropathy, dizziness  

 

lethargy, paraesthesia, hypoaesthesia, dysgeusia, 

disturbance in attention, memory impairment, somnolence  

 

syncope, convulsion, ageusia, sleep phase rhythm 

disturbance  

Eye disorders 

Uncommon  

 

Rare  

conjunctival hyperaemia, dry eye  

 

visual disturbance  

Ear and labyrinth disorders 

Uncommon  vertigo  

Cardiac disorders 



62 

 

Uncommon  

 

 

Rare  

myocardial infarction, angina pectoris, prolonged 

electrocardiogram QT, tachycardia  

 

acute myocardial infarction, sinus bradycardia, palpitations  

Vascular disorders 

Uncommon  hypertension, flushing  

Respiratory, thoracic and mediastinal disorders 

Uncommon  

 

Rare  

dyspnoea, cough, epistaxis, throat irritation  

 

rhinorrhoea  

Gastrointestinal disorders 

Very common  

 

Common  

 

 

 

Uncommon  

 

 

 

Rare 

diarrhoea  

 

vomiting, nausea, abdominal pain, increased blood 

amylase, dyspepsia, abdominal distension, flatulence  

 

pancreatitis, gastritis, gastrooesophageal reflux disease, 

aphthous stomatitis, retching, dry mouth, abdominal 

discomfort, constipation, increased lipase, eructation, oral 

dysaesthesia  

 

stomatitis, haematemesis, cheilitis, dry lip, coated tongue  

Hepatobiliary disorders 

Common  

 

Uncommon  

increased alanine aminotransferase  

 

hepatitis, cytolytic hepatitis, hepatic steatosis, 

hepatomegaly, increased transaminase, increased aspartate 

aminotransferase, increased blood bilirubin, increased 

blood alkaline phosphatase, increased gamma-

glutamyltransferase  

Skin and subcutaneous tissue disorders 

Common  

 

 

Uncommon  

 

 

 

Rare  

 

 

 

Not known  

rash (including macular, maculopapular, papular, 

erythematous and pruritic rash), pruritus  

 

angioedema, generalised rash, allergic dermatitis, urticaria, 

eczema, erythema, hyperhidrosis, night sweats, alopecia, 

acne, dry skin, nail pigmentation  

 

DRESS, Stevens-Johnson syndrome, erythema multiforme, 

dermatitis, seborrhoeic dermatitis, skin lesion, xeroderma  

 

toxic epidermal necrolysis, acute generalised 

exanthematous pustulosis  

Musculoskeletal and connective tissue disorders 

Uncommon  

 

 

 

Rare  

myalgia, osteonecrosis, muscle spasms, muscular 

weakness, arthralgia, pain in extremity, osteoporosis, 

increased blood creatine phosphokinase  

 

musculoskeletal stiffness, arthritis, joint stiffness  

Renal and urinary disorders 

Uncommon  

 

 

 

Rare  

acute renal failure, renal failure, nephrolithiasis, increased 

blood creatinine, proteinuria, bilirubinuria, dysuria, 

nocturia, pollakiuria  

 

decreased creatinine renal clearance  

Reproductive system and breast disorders 



63 

 

Uncommon  erectile dysfunction, gynaecomastia  

General disorders and administration site conditions 

Common  

 

Uncommon  

 

 

Rare  

asthenia, fatigue  

 

pyrexia, chest pain, peripheral oedema, malaise, feeling 

hot, irritability, pain  

 

chills, abnormal feeling, xerosis  

 

Adverse reactions observed with darunavir/cobicistat in adult patients 

 

MedDRA system organ class  

Frequency category  

Adverse reaction  

Immune system disorders 

Common 

 

Uncommon  

(drug) hypersensitivity  

 

immune reconstitution inflammatory syndrome  

Metabolism and nutrition disorders 

Common  anorexia, diabetes mellitus, hypercholesterolaemia, 

hypertriglyceridaemia, hyperlipidaemia  

Psychiatric disorders 

Common  abnormal dreams  

Nervous system disorders 

Very common  headache  

Gastrointestinal disorders 

Very common  

 

Common  

 

 

Uncommon  

diarrhoea, nausea  

 

vomiting, abdominal pain, abdominal distension, 

dyspepsia, flatulence, pancreatic enzymes increased  

 

pancreatitis acute  

Hepatobiliary disorders 

Common  

 

Uncommon  

hepatic enzyme increased  

 

hepatitis*, cytolytic hepatitis*  

Skin and subcutaneous tissue disorders 

Very common  

 

 

 

Common  

 

Rare  

 

 

Not known  

rash (including macular, maculopapular, papular, 

erythematous, pruritic rash, generalised rash, and 

allergic dermatitis)  

 

angioedema, pruritus, urticaria  

 

drug reaction with eosinophilia and systemic 

symptoms*, Stevens-Johnson syndrome*  

 

toxic epidermal necrolysis*, acute generalised 

exanthematous pustulosis*  

Musculoskeletal and connective tissue disorders 

Common  

 

Uncommon 

myalgia  

 

osteonecrosis* 



64 

 

Reproductive system and breast disorders 

Uncommon  gynaecomastia*  

General disorders and administration site conditions 

Common  

 

Uncommon  

fatigue  

 

asthenia  

Investigations 

Common  increased blood creatinine  
*
 these adverse drug reactions have not been reported in clinical trial experience with darunavir/cobicistat but have been 

noted with darunavir/ritonavir treatment and could be expected with darunavir/cobicistat too. 
 

Description of selected adverse reactions 

 

Rash 

In clinical trials, rash was mostly mild to moderate, often occurring within the first four weeks of 

treatment and resolving with continued dosing. In cases of severe skin reaction see the warning in 

section 4.4. In a single arm trial investigating darunavir 800 mg once daily in combination with 

cobicistat 150 mg once daily and other antiretrovirals 2.2% of patients discontinued treatment due to 

rash.  

 

During the clinical development program of raltegravir in treatment-experienced patients, rash, 

irrespective of causality, was more commonly observed with regimens containing darunavir/ritonavir 

+ raltegravir compared to those containing darunavir/ritonavir without raltegravir or raltegravir 

without darunavir/ritonavir. Rash considered by the investigator to be drug-related occurred at similar 

rates. The exposure-adjusted rates of rash (all causality) were 10.9, 4.2, and 3.8 per 100 patient-years 

(PYR), respectively; and for drug-related rash were 2.4, 1.1, and 2.3 per 100 PYR, respectively. The 

rashes observed in clinical studies were mild to moderate in severity and did not result in 

discontinuation of therapy (see section 4.4).  

 

Metabolic parameters 

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

4.4). 

 

Musculoskeletal abnormalities 

Increased CPK, myalgia, myositis and rarely, rhabdomyolysis have been reported with the use of 

protease inhibitors, particularly in combination with NRTIs.  

 

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).  

 

Immune reconstitution inflammatory syndrome 

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).  

 

Bleeding in haemophiliac patients 

There have been reports of increased spontaneous bleeding in haemophiliac patients receiving 

antiretroviral protease inhibitors (see section 4.4).  

 

Paediatric population 

 



65 

 

The safety assessment in paediatric patients is based on the 48-week analysis of safety data from three 

Phase II trials. The following patient populations were evaluated (see section 5.1):  

● 80 ART-experienced HIV-1 infected paediatric patients aged from 6 to 17 years and weighing at 

least 20 kg who received darunavir tablets with low dose ritonavir twice daily in combination 

with other antiretroviral agents.  

● 21 ART-experienced HIV-1 infected paediatric patients aged from 3 to < 6 years and weighing 

10 kg to < 20 kg (16 participants from 15 kg to < 20 kg) who received darunavir oral suspension 

with low dose ritonavir twice daily in combination with other antiretroviral agents. 

● 12 ART-naïve HIV-1 infected paediatric patients aged from 12 to 17 years and weighing at least 

40 kg who received darunavir tablets with low dose ritonavir once daily in combination with 

other antiretroviral agents (see section 5.1).  

 

Overall, the safety profile in these paediatric patients was similar to that observed in the adult 

population.  

 

Other special populations 

 

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

Among 1,968 treatment-experienced patients receiving darunavir co-administered with ritonavir 

600/100 mg twice daily, 236 patients were co-infected with hepatitis B or C. Co-infected patients were 

more likely to have baseline and treatment emergent hepatic transaminase elevations than those 

without chronic viral hepatitis (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 darunavir co-administered with cobicistat or low dose 

ritonavir is limited. Single doses up to 3,200 mg of darunavir as oral solution alone and up to 1,600 mg 

of the tablet formulation of darunavir in combination with ritonavir have been administered to healthy 

volunteers without untoward symptomatic effects.  

 

There is no specific antidote for overdose with darunavir. Treatment of overdose with darunavir 

consists of general supportive measures including monitoring of vital signs and observation of the 

clinical status of the patient. Since darunavir is highly protein bound, dialysis is unlikely to be 

beneficial in significant removal of the active substance. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antivirals for systemic use, protease inhibitors, ATC code: J05AE10.  

 

Mechanism of action 

 

Darunavir is an inhibitor of the dimerisation and of the catalytic activity of the HIV-1 protease (KD of 

4.5 x 10-12M). It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus 

infected cells, thereby preventing the formation of mature infectious virus particles. 

  

Antiviral activity in vitro  

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


66 

 

Darunavir exhibits activity against laboratory strains and clinical isolates of HIV-1 and laboratory 

strains of HIV-2 in acutely infected T-cell lines, human peripheral blood mononuclear cells and human 

monocytes/macrophages with median EC50 values ranging from 1.2 to 8.5 nM (0.7 to 5.0 ng/ml). 

Darunavir demonstrates antiviral activity in vitro against a broad panel of HIV-1 group M (A, B, C, D, 

E, F, G) and group O primary isolates with EC50 values ranging from < 0.1 to 4.3 nM.  

 

These EC50 values are well below the 50% cellular toxicity concentration range of 87 µM to 

> 100 µM.  

 

Resistance 

 

In vitro selection of darunavir-resistant virus from wild type HIV-1 was lengthy (> 3 years). The 

selected viruses were unable to grow in the presence of darunavir concentrations above 400 nM. 

Viruses selected in these conditions and showing decreased susceptibility to darunavir (range: 

23-50-fold) harboured 2 to 4 amino acid substitutions in the protease gene. The decreased 

susceptibility to darunavir of the emerging viruses in the selection experiment could not be explained 

by the emergence of these protease mutations.  

 

The clinical trial data from ART-experienced patients (TITAN trial and the pooled analysis of the 

POWER 1, 2 and 3 and DUET 1 and 2 trials) showed that virologic response to darunavir co-

administered with low dose ritonavir was decreased when 3 or more darunavir RAMs (V11I, V32I, 

L33F, I47V, I50V, I54L or M, T74P, L76V, I84V and L89V) were present at baseline or when these 

mutations developed during treatment. 

  

Increasing baseline darunavir fold change in EC50 (FC) was associated with decreasing virologic 

response. A lower and upper clinical cut-off of 10 and 40 were identified. Isolates with baseline FC ≤ 

10 are susceptible; isolates with FC > 10 to 40 have decreased susceptibility; isolates with FC > 40 are 

resistant (see Clinical results).  

 

Viruses isolated from patients on darunavir/ritonavir 600/100 mg twice daily experiencing virologic 

failure by rebound that were susceptible to tipranavir at baseline remained susceptible to tipranavir 

after treatment in the vast majority of cases. 

  

The lowest rates of developing resistant HIV virus are observed in ART-naïve patients who are treated 

for the first time with darunavir in combination with other ART.  

 

The table below shows the development of HIV-1 protease mutations and loss of susceptibility to PIs 

in virologic failures at endpoint in the ARTEMIS, ODIN and TITAN trials.  

 

  ARTEMIS 

Week 192 

ODIN 

Week 48 

TITAN 

Week 48 

  darunavir/ 

ritonavir 

800/100 mg 

once daily 

N=343 

darunavir/ ritonavir 

800/100 mg 

once daily 

N=294 

darunavir/ ritonavir 

600/100 mg 

twice daily 

N=296 

darunavir/ ritonavir 

600/100 mg 

twice daily 

N=298 

Total number of 

virologic failuresa, 

n (%) 

Rebounders  

Never suppressed 

subjects  

55 (16.0%) 

 

 

39 (11.4%) 

16 (4.7%) 

65 (22.1%) 

 

 

11 (3.7%) 

54 (18.4%) 

54 (18.2%) 

 

 

11 (3.7%) 

43 (14.5%) 

31 (10.4%) 

 

 

16 (5.4%) 

15 (5.0%) 

Number of subjects with virologic failure and paired baseline/endpoint genotypes, developing mutationsb at 

endpoint, n/N  



67 

 

Primary (major) PI 

mutations  

PI RAMs  

0/43 

 

4/43 

1/60 

 

7/60 

0/42 

 

4/42 

6/28 

 

10/28 

Number of subjects with virologic failure and paired baseline/endpoint phenotypes, showing loss of susceptibility 

to PIs at endpoint compared to baseline, n/N  

PI          

darunavir  

amprenavir  

atazanavir  

indinavir  

lopinavir  

saquinavir  

tipranavir  

0/39 

0/39 

0/39 

0/39 

0/39 

0/39 

0/39 

1/58 

1/58 

2/56 

2/57 

1/58 

0/56 

0/58 

0/41 

0/40 

0/40 

0/40 

0/40 

0/40 

0/41 

3/26 

0/22 

0/22 

1/24 

0/23 

0/22 

1/25 

a  TLOVR non-VF censored algorithm based on HIV-1 RNA < 50 copies/ml, except for TITAN (HIV-1 RNA < 400 

copies/ml)  
b IAS-USA lists 

 

Low rates of developing resistant HIV-1 virus were observed in ART-naïve patients who are treated 

for the first time with darunavir/cobicistat once daily in combination with other ART, and in ART-

experienced patients with no darunavir RAMs receiving darunavir/cobicistat in combination with 

other ART. The table below shows the development of HIV-1 protease mutations and resistance to PIs 

in virologic failures at endpoint in the GS-US-216-130 trial.  

 

  GS-US-216-130 

Week 48 

  Treatment-naïve 

darunavir/cobicistat 800/150 mg 

once daily 

N=295 

Treatment-experienced 

darunavir/cobicistat 800/150 mg 

once daily 

N=18 

Number of subjects with virologic failurea and genotype data that develop mutationsb at endpoint, n/N  

Primary (major) PI mutations  

PI RAMs  

0/8 

2/8 

1/7 

1/7 

Number of subjects with virologic failurea and phenotype data that show resistance to PIs at endpointc, n/N  

HIV PI  

darunavir  

amprenavir  

atazanavir  

indinavir  

lopinavir  

saquinavir  

tipranavir  

 

0/8 

0/8 

0/8 

0/8 

0/8 

0/8 

0/8 

 

0/7 

0/7 

0/7 

0/7 

0/7 

0/7 

0/7 

a Virogic failures were defined as: never suppressed: confirmed HIV-1 RNA < 1 log10 reduction from baseline and ≥ 50 

copies/ml at the week-8; rebound: HIV-1 RNA < 50 copies/ml followed by confirmed HIV-1 RNA to ≥ 400 copies/ml or 

confirmed > 1 log10 HIV-1 RNA increase from the nadir; discontinuations with HIV-1 RNA ≥ 400 copies/ml at last visit  
b IAS-USA lists  
c In GS-US216-130 baseline phenotype was not available 

 

Cross-resistance 

 

Darunavir FC was less than 10 for 90% of 3,309 clinical isolates resistant to amprenavir, atazanavir, 

indinavir, lopinavir, nelfinavir, ritonavir, saquinavir and/or tipranavir showing that viruses resistant to 

most PIs remain susceptible to darunavir.  

 



68 

 

In the virologic failures of the ARTEMIS trial no cross-resistance with other PIs was observed.  

In the virologic failures of the GS-US-216-130 trial no cross-resistance with other HIV PIs was 

observed.  

 

Clinical results 

 

The pharmacokinetic enhancing effect of cobicistat on darunavir was evaluated in a Phase I study in 

healthy subjects that were administered darunavir 800 mg with either cobicistat at 150 mg or ritonavir 

at 100 mg once daily. The steady-state pharmacokinetic parameters of darunavir were comparable 

when boosted with cobicistat versus ritonavir. For information on cobicistat, consult the cobicistat 

Summary of Product Characteristics.  

 

Adult patients 

 

Efficacy of darunavir 800 mg once daily co-administered with 150 mg cobicistat once daily in 

ART-naïve and ART-experienced patients  

 

GS-US-216-130 is a single arm, open-label, Phase III trial evaluating the pharmacokinetics, safety, 

tolerability, and efficacy of darunavir with cobicistat in 313 HIV-1 infected adult patients 

(295 treatment-naïve and 18 treatment-experienced). These patients received darunavir 800 mg once 

daily in combination with cobicistat 150 mg once daily with an investigator selected background 

regimen consisting of 2 active NRTIs.  

 

HIV-1 infected patients who were eligible for this trial had a screening genotype showing no darunavir 

RAMs and plasma HIV-1 RNA ≥ 1,000 copies/ml. The table below shows the efficacy data of the 

48 week analyses from the GS-US-216-130 trial:  

 
 

GS-US-216-130 

Outcomes at Week 48 Treatment-naïve 

darunavir/cobicistat 

800/150 mg once daily 

+ OBR 

N=295 

Treatment-experienced 

darunavir/cobicistat 

800/150 mg once daily 

+ OBR 

N=18 

All subjects 

darunavir/cobicistat 

800/150 mg once daily 

+ OBR 

N=313 

HIV-1 RNA 

< 50 copies/mla 

245 (83.1%) 8 (44.4%) 253 (80.8%) 

mean HIV-1 RNA log 

change from baseline (log10 

copies/ml)  

-3.01 -2.39 -2.97 

CD4+ cell count mean 

change from baselineb 

+174 +102 +170 

a Imputations according to the TLOVR algorithm  
b Last Observation Carried Forward imputation  

 

Efficacy of darunavir 800 mg once daily co-administered with 100 mg ritonavir once daily in ART-

naïve patients  

 

The evidence of efficacy of darunavir/ritonavir 800/100 mg once daily is based on the analyses of 

192 week data from the randomised, controlled, open-label Phase III trial ARTEMIS in antiretroviral 

treatment-naïve HIV-1 infected patients comparing darunavir/ritonavir 800/100 mg once daily with 

lopinavir/ritonavir 800/200 mg per day (given as a twice-daily or as a once-daily regimen). Both arms 

used a fixed background regimen consisting of tenofovir disoproxil fumarate 300 mg once daily and 

emtricitabine 200 mg once daily.  

 

The table below shows the efficacy data of the 48 week and 96 week analyses from the ARTEMIS 

trial:  



69 

 

ARTEMIS 
 

Week 48a Week 96b 

Outcomes Darunavir/ 

ritonavir 

800/100 mg 

once daily 

N=343 

Lopinavir/ 

ritonavir 

800/200 mg 

per day 

N=346 

Treatment 

difference 

(95% CI of 

difference) 

Darunavir/ 

ritonavir 

800/100 mg 

once daily 

N=343 

Lopinavir/ 

ritonavir 

800/200 mg 

per day 

N=346 

Treatment 

difference 

(95% CI of 

difference) 

HIV-1 RNA 

< 50 copies/mlc  

All patients  

 

With baseline 

HIV-RNA  

< 100,000  

With baseline 

HIV-RNA 

 ≥ 100,000  

With baseline 

CD4+ cell 

count < 200  

With baseline 

CD4+ cell 

count ≥ 200  

   

 

83.7%  

(287)  

85.8%  

(194/226)  

 

79.5%  

(93/117)  

 

79.4%  

(112/141)  

 

86.6%  

(175/202)   

   

 

78.3%  

(271)  

84.5%  

(191/226)  

 

66.7%  

(80/120)  

 

70.3%  

(104/148)  

 

84.3%  

(167/198)   

   

 

5.3%  

(-0.5; 11.2)d 

1.3%  

(-5.2; 7.9)d 

 

12.8%  

(1.6; 24.1)d 

 

9.2%  

(-0.8; 19.2)d 

 

2.3%  

(-4.6; 9.2)d 

  

   

 

79.0%  

(271)  

80.5%  

(182/226)  

 

76.1%  

(89/117)  

 

78.7%  

(111/141)  

 

79.2%  

(160/202)   

   

 

70.8%  

(245)  

75.2%  

(170/226)  

 

62.5%  

(75/120)  

 

64.9%  

(96/148)  

 

75.3%  

(149/198)   

   

 

8.2%  

(1.7; 14.7)d 

5.3%  

(-2.3; 13.0)d 

 

13.6%  

(1.9; 25.3)d 

 

13.9%  

(3.5; 24.2)d 

 

4.0%  

(-4.3; 12.2)d 

  

median CD4+ 

cell count 

change from 

baseline 

(x 106/l)e 

137  141   171  188   

a Data based on analyses at week 48  
b Data based on analyses at week 96  
c Imputations according to the TLOVR algorithm  
d Based on normal approximation to the difference in % response  
e Non-completer is failure imputation: patients who discontinued prematurely are imputed with a change equal to 0 

 

Non-inferiority in virologic response to the darunavir/ritonavir treatment, defined as the percentage of 

patients with plasma HIV-1 RNA level < 50 copies/ml, was demonstrated (at the pre-defined 12% 

non-inferiority margin) for both Intent-To-Treat (ITT) and On Protocol (OP) populations in the 

48 week analysis. These results were confirmed in the analyses of data at 96 weeks of treatment in the 

ARTEMIS trial. These results were sustained up to 192 weeks of treatment in the ARTEMIS trial.  

 

Efficacy of darunavir 800 mg once daily co-administered with 100 mg ritonavir once daily in 

ART-experienced patients  

 

ODIN is a Phase III, randomised, open-label trial comparing darunavir/ritonavir 800/100 mg once 

daily versus darunavir/ritonavir 600/100 mg twice daily in ART-experienced HIV-1 infected patients 

with screening genotype resistance testing showing no darunavir RAMs (i.e. V11I, V32I, L33F, I47V, 

I50V, I54M, I54L, T74P, L76V, I84V, L89V) and a screening HIV-1 RNA > 1,000 copies/ml. 

Efficacy analysis is based on 48 weeks of treatment (see table below). Both arms used an optimised 

background regimen (OBR) of ≥ 2 NRTIs.  

 

ODIN 

Outcomes Darunavir/ritonavir 

800/100 mg once 

daily + OBR 

N=294 

Darunavir/ritonavir 

600/100 mg twice 

daily + OBR 

N=296 

Treatment difference 

(95% CI of difference) 

HIV-1 RNA 

< 50 copies/mla 

72.1% (212)  

   

 

70.9% (210)  

   

 

1.2% (-6.1; 8.5)b 

   

 



70 

 

With Baseline HIV-1 

RNA (copies/ml)  

< 100,000  

≥ 100,000  

With Baseline CD4+ 

cell count (x 106/l)  

≥ 100  

< 100  

With HIV-1 clade  

Type B  

Type AE  

Type C  

Otherc 

 

77.6% (198/255)  

35.9% (14/39)  

   

 

75.1% (184/245)  

57.1% (28/49)  

   

70.4% (126/179)  

90.5% (38/42)  

72.7% (32/44)  

55.2% (16/29)  

 

73.2% (194/265)  

51.6% (16/31)  

   

 

72.5% (187/258)  

60.5% (23/38)  

   

64.3% (128/199)  

91.2% (31/34)  

78.8% (26/33)  

83.3% (25/30)  

 

4.4% (-3.0; 11.9)  

-15.7% (-39.2; 7.7)  

   

 

2.6% (-5.1; 10.3)  

-3.4% (-24.5; 17.8)  

   

6.1% (-3.4; 15.6)  

-0.7% (-14.0; 12.6)  

-6.1% (-2.6; 13.7)  

-28.2% (-51.0; -5.3)  

mean CD4+ cell count 

change from baseline  

(x 106/l)e 

108  112  -5d (-25; 16)  

a Imputations according to the TLOVR algorithm  
b Based on a normal approximation of the difference in % response  
c Clades A1, D, F1, G, K, CRF02_AG, CRF12_BF, and CRF06_CPX  
d Difference in means  
e Last Observation Carried Forward imputation 

 

At 48 weeks, virologic response, defined as the percentage of patients with plasma HIV-1 RNA level 

< 50 copies/ml, with darunavir/ritonavir 800/100 mg once daily treatment was demonstrated to be 

non-inferior (at the pre-defined 12% non-inferiority margin) compared to darunavir/ritonavir 

600/100 mg twice daily for both ITT and OP populations.  

 

Darunavir/ritonavir 800/100 mg once daily in ART-experienced patients should not be used in patients 

with one or more darunavir resistance associated mutations (DRV-RAMs) or HIV-1 RNA 

≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 106/l (see section 4.2 and 4.4). Limited data is 

available in patients with HIV-1 clades other than B.  

 

Paediatric patients 

 

ART-naïve paediatric patients from the age of 12 years to < 18 years, and weighing at least 40 kg 

DIONE is an open-label, Phase II trial evaluating the pharmacokinetics, safety, tolerability, and 

efficacy of darunavir with low dose ritonavir in 12 ART-naïve HIV-1 infected paediatric patients aged 

12 to less than 18 years and weighing at least 40 kg. These patients received darunavir/ritonavir 

800/100 mg once daily in combination with other antiretroviral agents. Virologic response was defined 

as a decrease in plasma HIV-1 RNA viral load of at least 1.0 log10 versus baseline.  

 

DIONE 

Outcomes at week 48 Darunavir/ritonavir  

N=12  

HIV-1 RNA < 50 copies/mla 83.3% (10)  

CD4+ percent change from baselineb  14  

CD4+ cell count mean change from baselineb 221  

≥ 1.0 log10 decrease from baseline in plasma viral load  100%  
a Imputations according to the TLOVR algorithm.  
b Non-completer is failure imputation: patients who discontinued prematurely are imputed with a change equal 

to 0. 

 

For additional clinical study results in ART-experienced adults and paediatric patients, refer to the 

Summary of Product Characteristics for darunavir 75 mg, 150 mg, 300 mg or 600 mg tablets.  

 

Pregnancy and postpartum 



71 

 

Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a 

background regimen was evaluated in a clinical trial of 36 pregnant women (18 in each arm) during 

the second and third trimesters, and postpartum. Virologic response was preserved throughout the 

study period in both arms. No mother to child transmission occurred in the infants born to the 

31 subjects who stayed on the antiretroviral treatment through delivery. There were no new clinically 

relevant safety findings compared with the known safety profile of darunavir/ritonavir in HIV-1 

infected adults (see sections 4.2, 4.4 and 5.2). 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetic properties of darunavir, co-administered with cobicistat or ritonavir, have been 

evaluated in healthy adult volunteers and in HIV-1 infected patients. Exposure to darunavir was higher 

in HIV-1 infected patients than in healthy subjects. The increased exposure to darunavir in HIV-1 

infected patients compared to healthy subjects may be explained by the higher concentrations of α1-

acid glycoprotein (AAG) in HIV-1 infected patients, resulting in higher darunavir binding to plasma 

AAG and, therefore, higher plasma concentrations.  

 

Darunavir is primarily metabolised by CYP3A. Cobicistat and ritonavir inhibit CYP3A, thereby 

increasing the plasma concentrations of darunavir considerably.  

 

For information on cobicistat pharmacokinetic properties, consult the cobicistat Summary of Product 

Characteristics.  

 

Absorption 

 

Darunavir was rapidly absorbed following oral administration. Maximum plasma concentration of 

darunavir in the presence of low dose ritonavir is generally achieved within 2.5-4.0 hours.  

 

The absolute oral bioavailability of a single 600 mg dose of darunavir alone was approximately 37% 

and increased to approximately 82% in the presence of 100 mg twice daily ritonavir. The overall 

pharmacokinetic enhancement effect by ritonavir was an approximate 14-fold increase in the systemic 

exposure of darunavir when a single dose of 600 mg darunavir was given orally in combination with 

ritonavir at 100 mg twice daily (see section 4.4).  

 

When administered without food, the relative bioavailability of darunavir in the presence of cobicistat 

or low dose ritonavir is lower as compared to intake with food. Therefore, darunavir tablets should be 

taken with cobicistat or ritonavir and with food. The type of food does not affect exposure to 

darunavir.  

 

Distribution 

 

Darunavir is approximately 95% bound to plasma protein. Darunavir binds primarily to plasma α1-acid 

glycoprotein.  

 

Following intravenous administration, the volume of distribution of darunavir alone was 88.1 ± 59.0 l 

(Mean ± SD) and increased to 131 ± 49.9 l (Mean ± SD) in the presence of 100 mg twice-daily 

ritonavir.  

 

Biotransformation 

 

In vitro experiments with human liver microsomes (HLMs) indicate that darunavir primarily 

undergoes oxidative metabolism. Darunavir is extensively metabolised by the hepatic CYP system and 

almost exclusively by isozyme CYP3A4. A 14C-darunavir trial in healthy volunteers showed that a 

majority of the radioactivity in plasma after a single 400/100 mg darunavir with ritonavir dose was due 

to the parent active substance. At least 3 oxidative metabolites of darunavir have been identified in 

humans; all showed activity that was at least 10-fold less than the activity of darunavir against wild 

type HIV.  



72 

 

 

Elimination 

 

After a 400/100 mg 14C-darunavir with ritonavir dose, approximately 79.5% and 13.9% of the 

administered dose of 14C-darunavir could be retrieved in faeces and urine, respectively. Unchanged 

darunavir accounted for approximately 41.2% and 7.7% of the administered dose in faeces and urine, 

respectively. The terminal elimination half-life of darunavir was approximately 15 hours when 

combined with ritonavir.  

The intravenous clearance of darunavir alone (150 mg) and in the presence of low dose ritonavir was 

32.8 l/h and 5.9 l/h, respectively.  

 

Special populations 

 

Paediatric population 

The pharmacokinetics of darunavir in combination with ritonavir taken twice daily in 74 treatment-

experienced paediatric patients, aged 6 to 17 years and weighing at least 20 kg, showed that the 

administered weight-based doses of darunavir/ritonavir resulted in darunavir exposure comparable to 

that in adults receiving darunavir/ritonavir 600/100 mg twice daily (see section 4.2).  

 

The pharmacokinetics of darunavir in combination with ritonavir taken twice daily in 14 treatment-

experienced paediatric patients, aged 3 to < 6 years and weighing at least 15 kg to < 20 kg, showed 

that weight-based dosages resulted in darunavir exposure that was comparable to that achieved in 

adults receiving darunavir/ritonavir 600/100 mg twice daily (see section 4.2).  

 

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 12 ART-naïve 

paediatric patients, aged 12 to < 18 years and weighing at least 40 kg, showed that darunavir/ritonavir 

800/100 mg once daily results in darunavir exposure that was comparable to that achieved in adults 

receiving darunavir/ritonavir 800/100 mg once daily. Therefore the same once daily dosage may be 

used in treatment-experienced adolescents aged 12 to < 18 years and weighing at least 40 kg without 

darunavir resistance associated mutations (DRV-RAMs)* and who have plasma HIV-1 RNA 

< 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 106/l (see section 4.2).  
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V  

 

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 10 treatment-

experienced paediatric patients, aged 3 to < 6 years and weighing at least 14 kg to < 20 kg, showed 

that weight-based dosages resulted in darunavir exposure that was comparable to that achieved in 

adults receiving darunavir/ritonavir 800/100 mg once daily (see section 4.2). In addition, 

pharmacokinetic modeling and simulation of darunavir exposures in paediatric patients across the ages 

of 3 to < 18 years confirmed the darunavir exposures as observed in the clinical studies and allowed 

the identification of weight-based darunavir/ritonavir once daily dosing regimens for paediatric 

patients weighing at least 15 kg that are either ART-naïve or treatment-experienced paediatric patients 

without DRV-RAMs* and who have plasma HIV-1 RNA < 100,000 copies/ml and CD4+ cell count 

≥ 100 cells x 106/l (see section 4.2).  
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V  

 

Elderly 

Population pharmacokinetic analysis in HIV infected patients showed that darunavir pharmacokinetics 

are not considerably different in the age range (18 to 75 years) evaluated in HIV infected patients 

(n=12, age ≥ 65) (see section 4.4). However, only limited data were available in patients above the age 

of 65 year.  

 

Gender 

Population pharmacokinetic analysis showed a slightly higher darunavir exposure (16.8%) in HIV 

infected females compared to males. This difference is not clinically relevant.  

 

Renal impairment 



73 

 

Results from a mass balance study with 14C-darunavir with ritonavir showed that approximately 7.7% 

of the administered dose of darunavir is excreted in the urine unchanged. 

  

Although darunavir has not been studied in patients with renal impairment, population 

pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly 

affected in HIV infected patients with moderate renal impairment (CrCl between 30-60 ml/min, n=20) 

(see sections 4.2 and 4.4).  

 

Hepatic impairment 

Darunavir is primarily metabolised and eliminated by the liver. In a multiple dose study with darunavir 

co-administered with ritonavir (600/100 mg) twice daily, it was demonstrated that the total plasma 

concentrations of darunavir in subjects with mild (Child-Pugh Class A, n=8) and moderate (Child-

Pugh Class B, n=8) hepatic impairment were comparable with those in healthy subjects. However, 

unbound darunavir concentrations were approximately 55% (Child-Pugh Class A) and 100% (Child-

Pugh Class B) higher, respectively. The clinical relevance of this increase is unknown therefore, 

darunavir should be used with caution. The effect of severe hepatic impairment on the 

pharmacokinetics of darunavir has not been studied (see sections 4.2, 4.3 and 4.4).  

 

Pregnancy and postpartum 

The exposure to total darunavir and ritonavir after intake of darunavir/ritonavir 600/100 mg twice 

daily and darunavir/ritonavir 800/100 mg once daily as part of an antiretroviral regimen was generally 

lower during pregnancy compared with postpartum. However, for unbound (i.e. active) darunavir, the 

pharmacokinetic parameters were less reduced during pregnancy compared to postpartum, due to an 

increase in the unbound fraction of darunavir during pregnancy compared to postpartum. 

 

Pharmacokinetic results of total darunavir after administration of darunavir/ritonavir at 600/100 mg 

twice daily as part of an antiretroviral regimen, during the second trimester of pregnancy, the third 

trimester of pregnancy and postpartum 

Pharmacokinetics of 

total darunavir 

(mean ± SD) 

Second trimester of 

pregnancy 

(n=12)a 

Third trimester of 

pregnancy 

(n=12) 

Postpartum  

(6-12 weeks) 

(n=12) 

Cmax, ng/ml 4,668 ± 1,097 5,328 ± 1,631 6,659 ± 2,364 

AUC12h, ng.h/ml 39,370 ± 9,597 45,880 ± 17,360 56,890 ± 26,340 

Cmin, ng/ml 1,922 ± 825 2,661 ± 1,269 2,851 ± 2,216 
a n=11 for AUC12h 

 

Pharmacokinetic results of total darunavir after administration of darunavir/ritonavir at 800/100 mg 

once daily as part of an antiretroviral regimen, during the second trimester of pregnancy, the third 

trimester of pregnancy and postpartum 

Pharmacokinetics of 

total darunavir (mean 

± SD) 

Second trimester of 

pregnancy 

(n=17) 

Third Trimester of 

pregnancy 

(n=15) 

Postpartum  

(6-12 weeks) 

(n=16) 

Cmax, ng/ml 4,964 ± 1,505 5,132 ± 1,198 7,310 ± 1,704 

AUC24h, ng.h/ml 62,289 ± 16,234 61,112 ± 13,790 92,116 ± 29,241 

Cmin, ng/ml 1,248 ± 542 1,075 ± 594 1,473 ± 1,141 

 

In women receiving darunavir/ritonavir 600/100 mg twice daily during the second trimester of 

pregnancy, mean intra-individual values for total darunavir Cmax, AUC12h and Cmin were 28%, 26% and 

26% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total 

darunavir Cmax, AUC12h and Cmin values were 18%, 16% lower and 2% higher, respectively, as 

compared with postpartum. 

 

In women receiving darunavir/ritonavir 800/100 mg once daily during the second trimester of 

pregnancy, mean intra-individual values for total darunavir Cmax, AUC24h and Cmin were 33%, 31% and 



74 

 

30% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total 

darunavir Cmax, AUC24h and Cmin values were 29%, 32% and 50% lower, respectively, as compared 

with postpartum. 

 

Treatment with darunavir/cobicistat 800/150 mg once daily during pregnancy results in low darunavir 

exposure. In women receiving darunavir/cobicistat during the second trimester of pregnancy, mean 

intra-individual values for total darunavir Cmax, AUC24h and Cmin were 49%, 56% and 92% lower, 

respectively, as compared with postpartum; during the third trimester of pregnancy, total darunavir 

Cmax, AUC24h and Cmin values were 37%, 50% and 89% lower, respectively, as compared with 

postpartum. The unbound fraction was also substantially reduced, including around 90% reductions of 

Cmin levels. The main cause of these low exposures is a marked reduction in cobicistat exposure as a 

consequence of pregnancy-associated enzyme induction (see below). 

 

Pharmacokinetic results of total darunavir after administration of darunavir/cobicistat  

800/150 mg once daily as part of an antiretroviral regimen, during the second trimester of 

pregnancy, the third trimester of pregnancy, and postpartum 

Pharmacokinetics of 

total darunavir (mean 

± SD) 

Second trimester of 

pregnancy 

(n=7) 

Third trimester of 

pregnancy 

(n=6) 

Postpartum  

(6-12 weeks) 

(n=6) 

Cmax, ng/mL 4,340 ± 1,616 4,910 ± 970 7,918 ± 2,199 

AUC24h, ng.h/mL 47,293 ± 19,058 47,991 ± 9,879 99,613 ± 34,862 

Cmin, ng/mL 168 ± 149 184 ± 99 1,538 ± 1,344 

The exposure to cobicistat was lower during pregnancy, potentially leading to suboptimal boosting of 

darunavir. During the second trimester of pregnancy, cobicistat Cmax, AUC24h, and Cmin were 50%, 

63%, and 83% lower, respectively, as compared with postpartum. During the third trimester of 

pregnancy, cobicistat Cmax, AUC24h, and Cmin, were 27%, 49%, and 83% lower, respectively, as 

compared with postpartum. 

 

5.3 Preclinical safety data 

 

Animal toxicology studies have been conducted at exposures up to clinical exposure levels with 

darunavir alone, in mice, rats and dogs and in combination with ritonavir in rats and dogs.  

 

In repeated-dose toxicology studies in mice, rats and dogs, there were only limited effects of treatment 

with darunavir. In rodents the target organs identified were the haematopoietic system, the blood 

coagulation system, liver and thyroid. A variable but limited decrease in red blood cell-related 

parameters was observed, together with increases in activated partial thromboplastin time.  

 

Changes were observed in liver (hepatocyte hypertrophy, vacuolation, increased liver enzymes) and 

thyroid (follicular hypertrophy). In the rat, the combination of darunavir with ritonavir lead to a small 

increase in effect on RBC parameters, liver and thyroid and increased incidence of islet fibrosis in the 

pancreas (in male rats only) compared to treatment with darunavir alone. In the dog, no major toxicity 

findings or target organs were identified up to exposures equivalent to clinical exposure at the 

recommended dose.  

 

In a study conducted in rats, the number of corpora lutea and implantations were decreased in the 

presence of maternal toxicity. Otherwise, there were no effects on mating or fertility with darunavir 

treatment up to 1,000 mg/kg/day and exposure levels below (AUC-0.5 fold) of that in human at the 

clinically recommended dose. Up to same dose levels, there was no teratogenicity with darunavir in 

rats and rabbits when treated alone nor in mice when treated in combination with ritonavir. The 

exposure levels were lower than those with the recommended clinical dose in humans. In a pre- and 

postnatal development assessment in rats, darunavir with and without ritonavir, caused a transient 

reduction in body weight gain of the offspring pre-weaning and there was a slight delay in the opening 

of eyes and ears. Darunavir in combination with ritonavir caused a reduction in the number of pups 

that exhibited the startle response on day 15 of lactation and a reduced pup survival during lactation. 



75 

 

These effects may be secondary to pup exposure to the active substance via the milk and/or maternal 

toxicity. No post weaning functions were affected with darunavir alone or in combination with 

ritonavir. In juvenile rats receiving darunavir up to days 23-26, increased mortality was observed with 

convulsions in some animals. Exposure in plasma, liver and brain was considerably higher than in 

adult rats after comparable doses in mg/kg between days 5 and 11 of age. After day 23 of life, the 

exposure was comparable to that in adult rats. The increased exposure was likely at least partly due to 

immaturity of the drug-metabolising enzymes in juvenile animals. No treatment related mortalities 

were noted in juvenile rats dosed at 1,000 mg/kg darunavir (single dose) on day 26 of age or at 

500 mg/kg (repeated dose) from day 23 to 50 of age, and the exposures and toxicity profile were 

comparable to those observed in adult rats.  

 

Due to uncertainties regarding the rate of development of the human blood brain barrier and liver 

enzymes, darunavir with low dose ritonavir should not be used in paediatric patients below 3 years of 

age. 

 

Darunavir was evaluated for carcinogenic potential by oral gavage administration to mice and rats up 

to 104 weeks. Daily doses of 150, 450 and 1,000 mg/kg were administered to mice and doses of 50, 

150 and 500 mg/kg were administered to rats. Dose-related increases in the incidences of 

hepatocellular adenomas and carcinomas were observed in males and females of both species. Thyroid 

follicular cell adenomas were noted in male rats. Administration of darunavir did not cause a 

statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or 

rats. The observed hepatocellular and thyroid tumours in rodents are considered to be of limited 

relevance to humans. Repeated administration of darunavir to rats caused hepatic microsomal enzyme 

induction and increased thyroid hormone elimination, which predispose rats, but not humans, to 

thyroid neoplasms. At the highest tested doses, the systemic exposures (based on AUC) to darunavir 

were between 0.4- and 0.7-fold (mice) and 0.7- and 1-fold (rats), relative to those observed in humans 

at the recommended therapeutic doses.  

 

After 2 years administration of darunavir at exposures at or below the human exposure, kidney 

changes were observed in mice (nephrosis) and rats (chronic progressive nephropathy).  

 

Darunavir was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including 

bacterial reverse mutation (Ames), chromosomal aberration in human lymphocytes and in vivo 

micronucleus test in mice.  

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core 

Silica, colloidal anhydrous 

Cellulose microcrystalline 

Crospovidone 

Sodium starch glycolate 

Hypromellose 

Magnesium stearate 

 

Tablet film-coat 

Polyvinyl alcohol partially hydrolysed 

Titanium dioxide (E171) 

Macrogol 

Talc 

 

 

6.2 Incompatibilities 

 



76 

 

Not applicable.  

 

6.3 Shelf life 

 

Darunavir Mylan 400 mg film-coated tablets  

3 years 

In-use shelf life after first opening HDPE bottle: 100 days.  

 

Darunavir Mylan 800 mg film-coated tablets 

3 years 

In-use shelf life after first opening HDPE bottle: 90 days. 

 

 

6.4 Special precautions for storage 

 

Darunavir Mylan 400 mg film-coated tablets 

This medicinal product does not require any special storage conditions.  

 

Darunavir Mylan 800 mg film-coated tablets 

PVC/PE/PVDC-Al blister pack 

Do not store above 25°C. 

 

Cold form PVC/Al/OPA-Al blister pack 

This medicinal product does not require any special storage conditions. 

 

HDPE bottle pack 

This medicinal product does not require any special storage conditions. 

 

 

6.5 Nature and contents of container 

 

Darunavir Mylan 400 mg film-coated tablets 

PVC/PE/PVDC-Al blister pack containing 30 and 60 tablets and 60x1 tablets. 

Cold form PVC/Al/OPA-Al blister pack containing 30 and 60 tablets and 60x1 tablets. 

HDPE bottle pack with a PP screw cap containing 60 and 100 tablets. 

 

Darunavir Mylan 800 mg film-coated tablets 

PVC/PE/PVDC-Al blister pack containing 30 tablets and 30x1 tablets. 

Cold form PVC/Al/OPA-Al blister pack containing 30 tablets and 30x1 tablets. 

HDPE bottle pack with a PP screw cap containing 30, 60, 90 tablets. 

 

Not all pack sizes may be marketed.  

 

6.6 Special precautions for disposal and other handling 

 

No special requirements.  

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  



77 

 

 

Darunavir Mylan 400 mg film-coated tablets 

EU/1/16/1140/022 

EU/1/16/1140/023 

EU/1/16/1140/024 

EU/1/16/1140/025 

EU/1/16/1140/026 

EU/1/16/1140/027 

EU/1/16/1140/028 

EU/1/16/1140/029 

 

Darunavir Mylan 800 mg film-coated tablets 

EU/1/16/1140/039 

EU/1/16/1140/040 

EU/1/16/1140/041 

EU/1/16/1140/042 

EU/1/16/1140/043 

EU/1/16/1140/044 

EU/1/16/1140/045 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 4th January 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

 

 

  

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


78 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



79 

 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers responsible for batch release 

 

Mylan Hungary Kft 

Mylan utca 1, Komárom, 2900, 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSURs) 

 

The requirements for submission of PSURs 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 marketing authorisation holder (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. 

  



80 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



81 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



82 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 75 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 75 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Blister carton 

480 film-coated tablets 

480 x 1 film-coated tablets 

 

Bottle carton 

480 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

<Bottles Only> Once opened, use within 100 days 

 

[On carton only:] 



83 

 

Open date: __________ 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/001 

EU/1/16/1140/002 

EU/1/16/1140/003 

EU/1/16/1140/004 

EU/1/16/1140/005 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 75 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 



84 

 

PC: 

SN: 

NN: 

 

 

  



85 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 75 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 75 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet  

 

480 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 100 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 



86 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/005  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



87 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 75 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



88 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 150 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 150 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Blister carton 

240 film-coated tablets 

240 x 1 film-coated tablets 

 

Bottle carton 

60 film-coated tablets 

240 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

<Bottles Only> Once opened, use within 100 days 

 



89 

 

[On carton only:] 

Open date: __________ 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/006  

EU/1/16/1140/007  

EU/1/16/1140/008  

EU/1/16/1140/009 

EU/1/16/1140/010 

EU/1/16/1140/011  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 150 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 



90 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



91 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 150 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 150 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet  

 

60 film-coated tablets 

240 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 100 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



92 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/010  

EU/1/16/1140/011  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



93 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 150 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



94 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 300 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 300 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

 

Blister carton 

30 film-coated tablets 

60 film-coated tablets 

120 film-coated tablets 

120 x 1 film-coated tablets 

 

Bottle carton 

30 film-coated tablets 

120 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 



95 

 

EXP 

<Bottles Only> Once opened, use within 100 days 

 

[On carton only:] 

Open date: __________ 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/012  

EU/1/16/1140/013  

EU/1/16/1140/014  

EU/1/16/1140/015  

EU/1/16/1140/016  

EU/1/16/1140/017 

EU/1/16/1140/018 

EU/1/16/1140/019 

EU/1/16/1140/020 

EU/1/16/1140/021  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 300 mg  



96 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



97 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 300 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 300 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet  

 

30 film-coated tablets 

120 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 100 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



98 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/020 

EU/1/16/1140/021  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



99 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 300 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



100 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 400 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 400 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablets 

 

Blister carton 

30 film-coated tablets 

60 film-coated tablets 

60 x 1 film-coated tablets 

 

Bottle carton 

60 film-coated tablets  

100 film-coated tablets  

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

<Bottles Only> Once opened, use within 100 days 



101 

 

[On carton only:] 

Open date: __________ 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/022  

EU/1/16/1140/023  

EU/1/16/1140/024  

EU/1/16/1140/025  

EU/1/16/1140/026  

EU/1/16/1140/027  

EU/1/16/1140/028  

EU/1/16/1140/029  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 400 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 



102 

 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



103 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 400 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 400 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet  

 

60 film-coated tablets 

100 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 100 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



104 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/028  

EU/1/16/1140/029  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



105 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 400 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



106 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 600 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 600 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Blister carton 

30 film-coated tablets 

60 film-coated tablets 

60 x 1 film-coated tablets 

 

Bottle carton 

30 film-coated tablets 

60 film-coated tablets 

90 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 



107 

 

<Bottles Only> Once opened, use within 100 days 

 

[On carton only:] 

Open date: __________ 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/030  

EU/1/16/1140/031   

EU/1/16/1140/032  

EU/1/16/1140/033  

EU/1/16/1140/034  

EU/1/16/1140/035  

EU/1/16/1140/036  

EU/1/16/1140/037  

EU/1/16/1140/038 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 600 mg  

 

 



108 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



109 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 600 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 600 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

30 film-coated tablets 

60 film-coated tablets 

90 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 100 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

 



110 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/036  

EU/1/16/1140/037  

EU/1/16/1140/038  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



111 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 600 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



112 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON (BLISTERS AND BOTTLES) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 800 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 800 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

Blister carton 

30 film-coated tablets 

30 x 1 film-coated tablets 

 

Bottle carton 

30 film-coated tablets  

60 film-coated tablets  

90 film-coated tablets  

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

<Bottles Only> Once opened, use within 90 days 



113 

 

[On carton only:] 

Open date: __________ 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

<PVC/PE/PVDC-Al blister pack only> 

Do not store above 25°C. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/039  

EU/1/16/1140/040  

EU/1/16/1140/041  

EU/1/16/1140/042  

EU/1/16/1140/043  

EU/1/16/1140/044  

EU/1/16/1140/045  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Darunavir Mylan 800 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 



114 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



115 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 800 mg film-coated tablets 

darunavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each film-coated tablet contains 800 mg of darunavir. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablet 

 

30 film-coated tablets 

60 film-coated tablets 

90 film-coated tablets 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

For oral use. 

 

Read the package leaflet before use. 

 

 

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

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

Once opened, use within 90 days 

 

 

9. SPECIAL STORAGE CONDITIONS 

. 



116 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

 

12. MARKETING AUTHORISATION NUMBERS  

 

EU/1/16/1140/043  

EU/1/16/1140/044  

EU/1/16/1140/045  

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

  



117 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Darunavir Mylan 800 mg film-coated tablets 

darunavir 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 

  



118 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



119 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 75 mg film-coated tablets 

 

darunavir 

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children of 3 years of age and above, and at least 15 kilogram 

body weight who are infected by HIV and who have already used other antiretroviral medicines.  

 

Darunavir must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. 

Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 

 

Medicine Purpose of the medicine 

Avanafil  to treat erectile dysfunction  



120 

 

Astemizole or terfenadine  to treat allergy symptoms  

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapine or sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine  

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

darunavir 

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection 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 



121 

 

improvement in the body’s immune response, enabling the body to fight infections that may 

have been present with no obvious symptoms.  

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan. 

 

Children  

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

  

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested 

with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of 

other medicines might need to be changed. Therefore always tell your doctor if you take other anti-

HIV medicines and follow your doctor’s instruction carefully on which medicines can be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 



122 

 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended.  

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects.  

- Buprenorphine/naloxone (medicines to treat opioid dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection) 
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders).  
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

 

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  

- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 
infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  

- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 
zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).  
 

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan’. 

 

Pregnancy and breast-feeding  



123 

 

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 

It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking darunavir. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking Darunavir Mylan and ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right once daily dose based on the weight of the child (see table below). 

This dose must not exceed the recommended adult dose, which is 800 milligram darunavir together 

with 100 milligram ritonavir once a day.  

The doctor will inform you on how much Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. 

 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right dose based on the weight of the child (see table below). The doctor 

will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must 

not exceed the recommended adult dose, which is 600 milligram darunavir together with 

100 milligram ritonavir two times per day or 800 milligram darunavir together with 100 milligram 

ritonavir once a day.  

The doctor will inform you on how many Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. Tablets of other strengths are available and your doctor may 

have prescribed a certain combination of tablets to construct the appropriate dosing regimen.  

Other forms of this medicine may be more suitable for children: ask your doctor or pharmacist. 

 

Twice daily dosing 

Weight One dose is 

between 15 and 30 kilograms  375 milligram darunavir + 50 milligram ritonavir 

twice a day  



124 

 

between 30 and 40 kilograms  450 milligram darunavir + 60 milligram ritonavir 

twice a day  

more than 40 kilograms*  600 milligram darunavir + 100 milligram 

ritonavir twice a day  
* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if Darunavir Mylan 

800 milligram once daily dosing may be used. This cannot be administered with these 75 milligram tablets. Other strengths 

of Darunavir Mylan are available. 

 

Once daily dosing 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  

 

 

Instructions for children  

- The child must take darunavir always together with ritonavir. Darunavir cannot work properly 
without ritonavir.  

- The child must take the appropriate doses of darunavir and ritonavir two times per day or once a 
day. If prescribed darunavir twice daily the child must take one dose in the morning, and one 

dose in the evening. Your child’s doctor will determine the appropriate dosing regimen for your 

child.  

- The child must take darunavir with food. Darunavir cannot work properly without food. The 
type of food is not important.  

- The child must swallow the tablets with a drink such as water or milk. 
 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this)  

You will require a different dose of darunavir which cannot be administered with these 75 milligram 

tablets. Other strengths of Darunavir Mylan are available.  

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)  

The dose is either:  

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 
600 milligram of darunavir) together with 100 milligram ritonavir twice daily.  

OR  

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 
800 milligram of darunavir) together with 100 milligram ritonavir once daily. Darunavir Mylan 

400 milligram and 800 milligram tablets are only to be used to construct the once daily 

800 milligram regimen.  

 

Please discuss with your doctor which dose is right for you. 

 

Instructions for adults  

- Take darunavir always together with ritonavir. Darunavir cannot work properly without 
ritonavir.  

- In the morning, take 600 milligram darunavir together with 100 milligram ritonavir.  
- In the evening, take 600 milligram darunavir together with 100 milligram ritonavir.  
- Take darunavir with food. Darunavir cannot work properly without food. The type of food is not 

important.  

- Swallow the tablets with a drink such as water or milk.  
- Darunavir Mylan 75 milligram and 150 milligram tablets have been developed for use in 

children, but can also be used in adults in some cases. 

 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 



125 

 

If you forget to take Darunavir Mylan 

If you notice within 6 hours, you must take the tablets immediately. Always take with ritonavir and 

food. If you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a 

double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking 

darunavir. Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below 

your ribs.  

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  



126 

 

- slowing down of the thyroid gland function. This can be seen in a blood test.  
- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

This medicine does not require any special storage conditions.  

 

For bottles: Once opened, use within 100 days. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

- The active substance is darunavir. Each tablet contains 75 milligrams of darunavir.  

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


127 

 

- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone, 
sodium starch glycolate, hypromellose, magnesium stearate. The film-coating contains 

polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

 

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 75 mg film-coated tablets are white to off-white, oval shaped with two curved sides, 

marked with M on one side and DV1 on the other side. 

 

Darunavir Mylan 75 mg film-coated tablets are available in blister packs containing 480 tablets and in 

plastic bottles containing 480 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturer 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 



128 

 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH 

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 



129 

 

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 

 

 

Other sources of information 

 

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

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

 

 

 

  

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


130 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 150 mg film-coated tablets 

 

darunavir  

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children of 3 years of age and above, and at least 15 kilogram 

body weight who are infected by HIV and who have already used other antiretroviral medicines.  

 

Darunavir must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. 

Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 

Medicine Purpose of the medicine 

Avanafil  to treat erectile dysfunction  

Astemizole or terfenadine  to treat allergy symptoms  



131 

 

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapineor sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine  

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin, simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

darunavir 

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection 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.  



132 

 

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan. 

 

Children  

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

  

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested 

with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of 

other medicines might need to be changed. Therefore always tell your doctor if you take other anti-

HIV medicines and follow your doctor’s instruction carefully on which medicines can be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended.  

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 



133 

 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects. 

- Buprenorphine/naloxone (medicines to treat opioide dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection) 
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders). 
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

 

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  
- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 

infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 

zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).  
 

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan. 

 

Pregnancy and breast-feeding  

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 



134 

 

It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking darunavir. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking Darunavir Mylan and ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right once daily dose based on the weight of the child (see table below). 

This dose must not exceed the recommended adult dose, which is 800 milligram darunavir together 

with 100 milligram ritonavir once a day.  

The doctor will inform you on how much Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. 

 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  
 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right dose based on the weight of the child (see table below). The doctor 

will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must 

not exceed the recommended adult dose, which is 600 milligram darunavir together with 

100 milligram ritonavir two times per day or 800 milligram darunavir together with 100 milligram 

ritonavir once a day.  

The doctor will inform you on how many Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. Tablets of other strengths are available and your doctor may 

have prescribed a certain combination of tablets to construct the appropriate dosing regimen.  

Other forms of this medicine may be more suitable for children: ask your doctor or pharmacist. 

 

Twice daily dosing 

Weight One dose is 

between 15 and 30 kilograms  375 milligram darunavir + 50 milligram ritonavir 

twice a day  

between 30 and 40 kilograms  450 milligram darunavir + 60 milligram ritonavir 

twice a day  

more than 40 kilograms*  600 milligram darunavir + 100 milligram 

ritonavir twice a day  



135 

 

* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if Darunavir Mylan 

800 milligram once daily dosing may be used. This cannot be administered with these 150 milligram tablets. Other strengths 

of Darunavir Mylan are available. 

 

Once daily dosing 

 

Weight 

One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  

 

Instructions for children  

- The child must take darunavir always together with ritonavir. Darunavir cannot work properly 
without ritonavir.  

- The child must take the appropriate doses of darunavir and ritonavir two times per day or once a 
day. If prescribed darunavir twice daily the child must take one dose in the morning, and one 

dose in the evening. Your child’s doctor will determine the appropriate dosing regimen for your 

child.  

- The child must take darunavir with food. Darunavir cannot work properly without food. The 
type of food is not important.  

- The child must swallow the tablets with a drink such as water or milk. 
 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this)  

You will require a different dose of darunavir which cannot be administered with these 150 milligram 

tablets. Other strengths of Darunavir Mylan are available.  

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)  

The dose is either:  

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 
600 milligram of darunavir) together with 100 milligram ritonavir twice daily.  

OR  

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 
800 milligram of darunavir) together with 100 milligram ritonavir once daily. Darunavir Mylan 

400 milligram and 800 milligram tablets are only to be used to construct the once daily 

800 milligram regimen.  

 

Please discuss with your doctor which dose is right for you. 

 

Instructions for adults  

- Take darunavir always together with ritonavir. Darunavir cannot work properly without 
ritonavir.  

- In the morning, take 600 milligram darunavir together with 100 milligram ritonavir.  
- In the evening, take 600 milligram darunavir together with 100 milligram ritonavir.  
- Take darunavir with food. Darunavir cannot work properly without food. The type of food is not 

important.  

- Swallow the tablets with a drink such as water or milk.  
- Darunavir Mylan 75 milligram and 150 milligram tablets have been developed for use in 

children, but can also be used in adults in some cases. 

 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 

If you forget to take Darunavir Mylan 



136 

 

If you notice within 6 hours, you must take the tablets immediately. Always take with ritonavir and 

food. If you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a 

double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicines make you feel better. Even when you feel better, do not stop taking darunavir. 

Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort  on your right side below 

your ribs.  

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  
- slowing down of the thyroid gland function. This can be seen in a blood test.  



137 

 

- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

This medicine does not require any special storage conditions.  

 

For bottles: Once opened, use within 100 days. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

- The active substance is darunavir. Each tablet contains 150 milligram of darunavir.  
- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone, 

sodium starch glycolate, hypromellose, magnesium stearate. The film-coating contains 

polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

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


138 

 

  

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 150 mg film-coated tablets are white to off-white, capsule shaped, with two curved 

sides, marked with M on one side and DV2 on the other side. 

 

Darunavir Mylan 150 mg film-coated tablets are available in blister packs containing 240 tablets and 

in plastic bottles containing 60 and 240 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturers 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 



139 

 

Deutschland 

Mylan Healthcare GmbH 

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.   

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 

 

 



140 

 

Other sources of information 

 

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

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

  

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


141 

 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 300 mg film-coated tablets 

 

darunavir  

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children of 3 years of age and above, and at least 15 kilogram 

body weight who are infected by HIV and who have already used other antiretroviral medicines.  

 

Darunavir must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. 

Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 

 



142 

 

Medicine Purpose of the medicine 

Avanafil  to treat erectile dysfunction  

Astemizole or terfenadine  to treat allergy symptoms  

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapine or sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine  

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin,simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

Darunavir Mylan  

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection and a history of 

opportunistic infection, signs and symptoms of inflammation from previous infections may 



143 

 

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.  

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan. 

 

Children  

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

  

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested 

with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of 

other medicines might need to be changed. Therefore always tell your doctor if you take other anti-

HIV medicines and follow your doctor’s instruction carefully on which medicines can be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaide, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 



144 

 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended.  

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle demage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects. 

- Buprenorphine/naloxone (medicines to treat opioide dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection)  
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders). 
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

 

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  
- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 

infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 

zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).  
 

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan’. 

 

Pregnancy and breast-feeding  



145 

 

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 
It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking Darunavir Mylan. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking Darunavir Mylan and ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this)  

You will require a different dose of darunavir which cannot be administered with these 300 milligram 

tablets. Other strengths of Darunavir Mylan are available.  

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)  

The dose is either:  

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 
600 milligram of darunavir) together with 100 milligram ritonavir twice daily.  

OR  

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 
800 milligram of darunavir) together with 100 milligram ritonavir once daily. Darunavir Mylan 

400 milligram and 800 milligram tablets are only to be used to construct the once daily 

800 milligram regimen.  

 

Please discuss with your doctor which dose is right for you. 

 

Instructions for adults  

- Take darunavir always together with ritonavir. Darunavir cannot work properly without 
ritonavir.  

- In the morning, take two 300 milligram darunavir tablets together with 100 milligram ritonavir.  
- In the evening, take two 300 milligram darunavir tablets together with 100 milligram ritonavir.  
- Take darunavir with food. Darunavir cannot work properly without food. The type of food is not 

important.  

- Swallow the tablets with a drink such as water or milk.  
- Darunavir 75 milligram and 150 milligram tablets have been developed for use in children, but 

can also be used in adults in some cases. 

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken 

antiretroviral medicines before (your child’s doctor will determine this)  



146 

 

The doctor will work out the right once daily dose based on the weight of the child (see table below). 

This dose must not exceed the recommended adult dose, which is 800 milligram darunavir together 

with 100 milligram ritonavir once a day.  

The doctor will inform you on how much Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. 

 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  
 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right dose based on the weight of the child (see table below). The doctor 

will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must 

not exceed the recommended adult dose, which is 600 milligram darunavir together with 

100 milligram ritonavir two times per day or 800 milligram darunavir together with 100 milligram 

ritonavir once a day.  

The doctor will inform you on how many Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. Tablets of lower strengths are available and your doctor may 

have prescribed a certain combination of tablets to construct the appropriate dosing regimen.  

Other forms of this medicine may be more suitable for children: ask your doctor or pharmacist. 

 

Twice daily dosing 

Weight One dose is 

between 15 and 30 kilograms  375 milligram darunavir + 50 milligram ritonavir 

twice a day  

between 30 and 40 kilograms  450 milligram darunavir + 60 milligram ritonavir 

twice a day  

more than 40 kilograms*  600 milligram darunavir + 100 milligram 

ritonavir twice a day  
* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if Darunavir Mylan 

800 milligram once daily dosing may be used. This cannot be administered with these 300 milligram tablets. Other 

strengths of Darunavir Mylan are available. 

 

Once daily dosing 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  

 

Instructions for children  

- The child must take darunavir always together with ritonavir. Darunavir cannot work properly 
without ritonavir.  

- The child must take the appropriate doses of darunavir and ritonavir two times per day or once a 
day. If prescribed darunavir twice daily the child must take one dose in the morning, and one 

dose in the evening. Your child’s doctor will determine the appropriate dosing regimen for your 

child.  

- The child must take darunavir with food. Darunavir cannot work properly without food. The 
type of food is not important.  

- The child must swallow the tablets with a drink such as water or milk. 
 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 



147 

 

If you forget to take Darunavir Mylan 

If you notice within 6 hours, you must take the tablets immediately. Always take with ritonavir and 

food. If you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a 

double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking 

Darunavir Mylan. Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

During HIV therapy there may be an incease 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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomforton your right side below 

your ribs.  

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  



148 

 

- slowing down of the thyroid gland function. This can be seen in a blood test.  
- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

This medicine does not require any special storage conditions.  

 

For bottles: Once opened, use within 100 days. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

- The active substance is darunavir. Each tablet contains 300 milligram of darunavir.  

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


149 

 

- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone 
(Type A), sodium starch glycolate, hypromellose, magnesium stearate. The film-coating 

contains polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

  

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 300 mg film-coated tablets are white to off-white, oval shaped, with two curved 

sides, marked with M on one side and DV3 on the other side. 

 

Darunavir Mylan 300 mg film-coated tablets are available in blister packs containing 30, 60 and 

120 tablets and in plastic bottles containing 30 and 120 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturer 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 



150 

 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH 

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 



151 

 

Latvija* 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 

 

Other sources of information 

 

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

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

  

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


152 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 400 mg film-coated tablets 

 

darunavir 

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children 3 years of age and above, at least 40 kilograms body 

weight) who are infected by HIV and  

- who have not used antiretroviral medicines before.  
- in certain patients who have used antiretroviral medicines before (your doctor will determine 

this). 

 

Darunavir must be taken in combination with a low dose of cobicistat or ritonavir and other anti-HIV 

medicines. Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to cobicistat or ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 

Medicine Purpose of the medicine 



153 

 

Avanafil  to treat erectile dysfunction  

Astemizole or terfenadine  to treat allergy symptoms  

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapine or sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine  

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin, simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

darunavir  

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection 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 



154 

 

improvement in the body’s immune response, enabling the body to fight infections that may 

have been present with no obvious symptoms.  

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan. 

 

Children and adolescents 

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

 

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with cobicistat or ritonavir has 

not been tested with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some 

cases dosage of other medicines might need to be changed. Therefore always tell your doctor if you 

take other anti-HIV medicines and follow your doctor’s instruction carefully on which medicines can 

be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 



155 

 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended.  

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects. 

- Buprenorphine/naloxone (medicines to treat opioid dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection) 
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders). 
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  

- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 
infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 

zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)  
- Metformin (to treat type 2 diabetes). 
 

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan. 

 

Pregnancy and breast-feeding  



156 

 

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor.  Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 
It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking darunavir. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking darunavir and cobicistat or ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Darunavir 400 mg tablets are only to be used to construct the once daily 800 mg regimen. 

 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this) 

The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of Darunavir Mylan 

or 1 tablet containing 800 milligram of Darunavir Mylan) once daily. 

You must take darunavir every day and always in combination with 150 milligram of cobicistat or 

100 milligram of ritonavir and with food. Darunavir cannot work properly without cobicistat or 

ritonavir and food. You must eat a meal or a snack within 30 minutes prior to taking your darunavir 

and cobicistat or ritonavir. The type of food is not important. Even if you feel better, do not stop taking 

darunavir and cobicistat or ritonavir without talking to your doctor. 

 

Instructions for adults 

- Take two 400 milligram tablets at the same time, once a day, every day. 

- Take darunavir always together with 150 milligram of cobicistat or 100 milligram of ritonavir. 

- Take darunavir with food. 

- Swallow the tablets with a drink such as water or milk. 

- Take your other HIV medicines used in combination with darunavir and cobicistat or ritonavir 

as recommended by your doctor. 

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this) 

The dose is either: 

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 

800 milligram of darunavir) together with 150 milligram cobicistat or 100 milligram ritonavir 

once daily. 

OR 

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 

600 milligram of darunavir) together with 100 milligram ritonavir twice daily. 

 

Please discuss with your doctor which dose is right for you. 

 



157 

 

Dose for children 3 years of age and above, weighing more than 40 kilograms who have not 

taken antiretroviral medicines before (your child’s doctor will determine this)  

- The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of darunavir or 

1 tablet containing 800 milligram of darunavir) together with 100 milligram ritonavir once daily. 

Dose for children 3 years of age and above, weighing more than 40 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The dose is either: 

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 

800 milligram of darunavir) together with 100 milligram ritonavir once daily. 

OR 

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 

600 milligram of darunavir) together with 100 milligram ritonavir twice daily. 

 

Please discuss with your doctor which dose is right for you.  

 

Instructions for children 3 years of age and above, weighing more than 40 kilograms 

- Take 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet 

containing 800 milligram of darunavir) at the same time, once a day, every day. 

- Take darunavir always together with 100 milligram of ritonavir. 

- Take darunavir with food. 

- Swallow the tablets with a drink such as water or milk. 

- Take your other HIV medicines used in combination with darunavir and ritonavir as 

recommended by your doctor. 

 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 

If you forget to take Darunavir Mylan 

If you notice within 12 hours, you must take the tablets immediately. Always take with cobicistat or 

ritonavir and food. If you notice after 12 hours, then skip the intake and take the next doses as usual. 

Do not take a double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking 

Darunavir Mylan. Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below 

your ribs.  

 



158 

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  
- slowing down of the thyroid gland function. This can be seen in a blood test.  
- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  



159 

 

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

This medicine does not require any special storage conditions.  

 

For bottles: Once opened, use within 100 days. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

- The active substance is darunavir. Each tablet contains 400 milligrams of darunavir.  
- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone, 

sodium starch glycolate, hypromellose, magnesium stearate. The film-coating contains 

polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

  

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 400 mg film-coated tablets are white to off-white, oval shaped with two curved 

sides, marked with M on one side and DV4 on the other side. 

 

Darunavir Mylan 400 mg film-coated tablets are available blister packs containing 30 and 60 tablets 

and in the HDPE bottles of 60 and 100 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturer 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

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


160 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH  

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 



161 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 

 

Other sources of information 

 

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

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

 

 

 

  

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


162 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 600 mg film-coated tablets 

 

darunavir  

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children of 3 years of age and above, and at least 15 kilogram 

body weight who are infected by HIV and who have already used other antiretroviral medicines.  

Darunavir must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. 

Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 

 

Medicine Purpose of the medicine 

Avanafil  to treat erectile dysfunction  



163 

 

Astemizole or terfenadine  to treat allergy symptoms  

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapineor sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine 

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin, simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

Darunavir Mylan  

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

 

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection and a history of 

opportunistic infection, signs and symptoms of inflammation from previous infections may occur 



164 

 

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.  

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan. 

 

Children  

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

  

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested 

with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of 

other medicines might need to be changed. Therefore always tell your doctor if you take other anti-

HIV medicines and follow your doctor’s instruction carefully on which medicines can be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 



165 

 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended.  

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects. 

- Buprenorphine/naloxone (medicines to treat opioid dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection) 
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders).  
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

 

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  

- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 
infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 

zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).  
 

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan. 

 

Pregnancy and breast-feeding  



166 

 

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 
It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking Darunavir Mylan. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking Darunavir Mylan and ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this)  

You will require a different dose of darunavir which cannot be administered with these 600 milligram 

tablets. Other strengths of Darunavir Mylan are available.  

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)  

The dose is either:  

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 
600 milligram of darunavir) together with 100 milligram ritonavir twice daily.  

OR  

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 
800 milligram of darunavir) together with 100 milligram ritonavir once daily. Darunavir Mylan 

400 milligram and 800 milligram tablets are only to be used to construct the once daily 800 

milligram regimen.  

 

Please discuss with your doctor which dose is right for you. 

 

Instructions for adults  

- Take darunavir always together with ritonavir. Darunavir cannot work properly without 
ritonavir.  

- In the morning, take one 600 milligram darunavir tablet together with 100 milligram ritonavir.  
- In the evening, take one 600 milligram darunavir tablet together with 100 milligram ritonavir.  
- Take darunavir with food. Darunavir cannot work properly without food. The type of food is not 

important.  

- Swallow the tablets with a drink such as water or milk.  
- Darunavir Mylan 75 milligram and 150 milligram tablets have been developed for use in 

children, but can also be used in adults in some cases. 

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken 

antiretroviral medicines before (your child’s doctor will determine this)  



167 

 

The doctor will work out the right once daily dose based on the weight of the child (see table below). 

This dose must not exceed the recommended adult dose, which is 800 milligram darunavir together 

with 100 milligram ritonavir once a day.  

The doctor will inform you on how much Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. 

 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  

 

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The doctor will work out the right dose based on the weight of the child (see table below). The doctor 

will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must 

not exceed the recommended adult dose, which is 600 milligram darunavir together with 

100 milligram of ritonavir two times per day or 800 milligram darunavir together with 100 milligram 

ritonavir once a day.  

The doctor will inform you on how many Darunavir Mylan tablets and how much ritonavir (capsules, 

tablets or solution) the child must take. Tablets of lower strengths are available to construct the 

appropriate dosing regimen.  

Other forms of this medicine may be more suitable for children: ask your doctor or pharmacist. 

 

Twice daily dosing 

 

Weight One dose is 

between 15 and 30 kilograms  375 milligram darunavir + 50 milligram ritonavir 

twice a day  

between 30 and 40 kilograms  450 milligram darunavir + 60 milligram ritonavir 

twice a day  

more than 40 kilograms*  600 milligram darunavir + 100 milligram 

ritonavir twice a day  
* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if Darunavir Mylan 

800 milligram once daily dosing may be used. This cannot be administered with these 600 milligram tablets. Other 

strengths of Darunavir Mylan are available. 

 

Once daily dosing 

Weight One darunavir dose is One ritonavira dose is 

between 15 and 30 kilograms  600 milligram  100 milligram  

between 30 and 40 kilograms  675 milligram  100 milligram  

more than 40 kilograms  800 milligram  100 milligram  
a ritonavir oral solution: 80 milligram per milliliter  

 

Instructions for children  

- The child must take darunavir always together with ritonavir. Darunavir cannot work properly 
without ritonavir.  

- The child must take the appropriate doses of darunavir and ritonavir two times per day or once a 
day. If prescribed darunavir twice daily the child must take one dose in the morning, and one 

dose in the evening. Your child’s doctor will determine the appropriate dosing regimen for your 

child.  

- The child must take darunavir with food. Darunavir cannot work properly without food. The 
type of food is not important.  

- The child must swallow the tablets with a drink such as water or milk. 
- Darunavir Mylan 75 mg and 150 mg tablets have been developed for use in children weighing 

less than 40 kilograms, but can also be used in adults in some cases. 

 



168 

 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 

If you forget to take Darunavir Mylan 

If you notice within 6 hours, you must take your missed dose immediately. Always take with 

ritonavir and food. If you notice after 6 hours, then skip the intake and take the next doses as usual. 

Do not take a double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicine may make you feel better. Even when you feel better, do not stop taking Darunavir 

Mylan. Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below 

your ribs.  

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  



169 

 

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  
- slowing down of the thyroid gland function. This can be seen in a blood test.  
- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

This medicine does not require any special storage conditions.  

 

For bottles: Once opened, use within 100 days. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

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


170 

 

- The active substance is darunavir. Each tablet contains 600 milligram of darunavir.  
- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone, 

sodium starch glycolate, hypromellose, magnesium stearate. The film-coating contains 

polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

 

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 600 mg film-coated tablets are white to off-white, oval shaped, with two curved 

sides, marked with M on one side and DV5 on the other side. 

 

Darunavir Mylan 600 mg film-coated tablets are available in blister packs containing 30 and 60 tablets 

and in plastic bottles containing 30, 60 and 90 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturers 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 



171 

 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH  

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY  

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 



172 

 

 

Other sources of information 

 

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

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

 

  

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


173 

 

Package leaflet: Information for the user 

 

Darunavir Mylan 800 mg film-coated tablets 

 

darunavir  

 

 

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, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

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

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

3. How to take Darunavir Mylan 

4. Possible side effects 

5. How to store Darunavir Mylan  

6. Contents of the pack and other information 

 

 

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

What is Darunavir Mylan? 

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used 

in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of 

medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. 

This will improve your immune system and reduces the risk of developing illnesses linked to HIV 

infection. 

 

What it is used for?  

Darunavir is used to treat adults and children (3 years of age and above, at least 40 kilograms body 

weight) who are infected by HIV and  

- who have not used antiretroviral medicines before.  
- in certain patients who have used antiretroviral medicines before (your doctor will determine 

this). 

 

Darunavir must be taken in combination with a low dose of cobicistat or ritonavir and other anti-HIV 

medicines. Your doctor will discuss with you which combination of medicines is best for you. 

 

 

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

Do not take Darunavir Mylan 

 

- if you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 
6) or to cobicistat or ritonavir.  

- if you have severe liver problems. Ask your doctor if you are unsure about the severity of your 
liver disease. Some additional tests might be necessary. 

 

Do not combine Darunavir Mylan with any of the following medicines  

If you are taking any of these, ask your doctor about switching to another medicine. 



174 

 

Medicine Purpose of the medicine 

Avanafil  to treat erectile dysfunction  

Astemizole or terfenadine  to treat allergy symptoms  

Triazolam and oral (taken by mouth) midazolam  to help you sleep and/or relieve anxiety  

Cisapride  to treat some stomach conditions  

Colchicine (if you have kidney and/or liver 

problems)  

to treat gout or familial Mediterranean fever 

Lurasidone, pimozide, quetiapine or sertindole  to treat psychiatric conditions  

Ergot alkaloids like ergotamine, 

dihydroergotamine, ergometrine and 

methylergonovine  

to treat migraine headaches  

Amiodarone, bepridil, dronedarone, ivabradine, 

quinidine, ranolazine 

to treat certain heart disorders e.g. abnormal heart 

beat  

Lovastatin, simvastatin and lomitapide to lower cholesterol levels  

Rifampicin  to treat some infections such as tuberculosis  

The combination product lopinavir/ritonavir  this anti-HIV medicine belongs to the same class as 

Darunavir Mylan  

Elbasvir/grazoprevir to treat hepatitis C infection 

Alfuzosin  to treat enlarged prostate  

Sildenafil  to treat high blood pressure in the pulmonary 

circulation  

Dabigatran, ticagrelor to help stop the clumping of platelets in the 

treatment of patients with a history of a heart attack  

Naloxegol to treat opioid induced constipation 

Dapoxetine to treat premature ejaculation 

Domperidone to treat nausea and vomiting 

 

Do not combine darunavir with products that contain St John’s wort (Hypericum perforatum). 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.  

 

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, 

although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the 

precautions needed to avoid infecting other people.  

 

People taking darunavir may still develop infections or other illnesses associated with HIV infection. 

You must keep in regular contact with your doctor.  

 

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or 

potentially life-threatening. Please contact your doctor whenever you develop a rash.  

 

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) 

may occur more frequently than in patients taking either medicine separately.  

 

Tell your doctor about your situation BEFORE and DURING your treatment  

Make sure that you check the following points and tell your doctor if any of these apply to you.  

- Tell your doctor if you have had problems with your liver before, including hepatitis B or C 
infection. Your doctor may evaluate how severe your liver disease is before deciding if you can 

take darunavir.  

- Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.  
- Tell your doctor immediately if you notice any symptoms of infection (for example enlarged 

lymph nodes and fever). In some patients with advanced HIV infection and a history of 

opportunistic infection, signs and symptoms of inflammation from previous infections may 



175 

 

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.  

- 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 the 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.  

- Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.  
- Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).  
- Tell your doctor if you notice any musculoskeletal problems. 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. 

 

Elderly 

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this 

age group, please discuss with your doctor if you can use Darunavir Mylan.  

 

Children and adolescents 

Darunavir Mylan 800 mg tablets is not for use in children younger than 3 years of age or weighing less 

than 40 kilograms. 

 

Other medicines and Darunavir Mylan 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.  

 

There are some medicines that you must not combine with darunavir. These are mentioned above 

under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’ 

 

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. 

NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase 

inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with cobicistat or ritonavir has 

not been tested with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some 

cases dosage of other medicines might need to be changed. Therefore always tell your doctor if you 

take other anti-HIV medicines and follow your doctor’s instruction carefully on which medicines can 

be combined.  

 

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor 

if you take:  

- Phenobarbital, phenytoin (to prevent seizures)  
- Dexamethasone (corticosteroid)  
- Efavirenz (HIV infection)  
- Boceprevir (hepatitis C infection)  
- Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)  
- Saquinavir (HIV infection).  

 

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take:  

- Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, 
mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the 

therapeutic effect or side effects of these medicines may be increased.  



176 

 

- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic 
effect or side effects may be altered; your doctor may have to check your blood. 

- Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might 
reduce its effectiveness. When used for birth control, alternative methods of non-hormonal 

contraception are recommended. 

- Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels 
by drospirenone. 

- Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage 
might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for 

your specific situation.  

- Clarithromycin (antibiotic)  
- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as 

the therapeutic effect or side effects of these medicines might be increased. Your doctor might 

want to do some additional tests.  

- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, 
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 

diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory 

conditions. If alternatives cannot be used, its use should only take place after medical evaluation 

and under close monitoring by your doctor for corticosteroid side effects. 

- Buprenorphine/naloxone (medicines to treat opioid dependence)  
- Salmeterol (medicine to treat asthma)  
- Artemether/lumefantrine (a combination medicine to treat malaria)  
- Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)  
- Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder 

called pulmonary arterial hypertension) 

- Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection)  
- Fentanyl, oxycodone, tramadol (to treat pain) 
- Fesoterodine, solifenacin (to treat urologic disorders). 
 

The dosage of other medicines might need to be changed since either their own or darunavir’s 

therapeutic effect or side effects may be influenced when combined.  

 

Tell your doctor if you take:  

- Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)  
- Digoxin (to treat certain heart disorders)  
- Clarithromycin (antibiotic)  
- Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal 

infections). Voriconazole should only be taken after medical evaluation.  

- Rifabutin (against bacterial infections)  
- Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary 

circulation)  

- Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat 
depression and anxiety)  

- Maraviroc (to treat HIV infection)  
- Methadone (to treat opiate dependance)  
- Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)  
- Colchicine (to treat gout or familial Mediterranean fever)  
- Bosentan (to treat high blood pressure in the pulmonary circulation)  
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, 

zoldipem (sedative agents)  

- Perphenazine, risperidone, thioridazine (to treat psychiatric conditions) 
- Metformin (to treat type 2 diabetes). 
This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 

taking. 

 

Darunavir Mylan with food and drink 

See section 3 ‘How to take Darunavir Mylan. 



177 

 

 

Pregnancy and breast-feeding  

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-

feeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically 

directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat. 

 
 It is recommended that HIV infected women must not breast-feed their infants because of both the 

possibility of your baby becoming infected with HIV through your breast milk and because of the 

unknown effects of the medicine on your baby.  

 

Driving and using machines 

Do not operate machines or drive if you feel dizzy after taking darunavir. 

 

Darunavir Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Darunavir Mylan 
 

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has 

told you. Check with your doctor, pharmacist or nurse if you are not sure.  

Even if you feel better, do not stop taking darunavir and cobicistat or ritonavir without talking to your 

doctor.  

 

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be 

stopped without instruction of the doctor.  

 

Darunavir Mylan 800 mg tablets are intended for once daily use only. 

 

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine 

this) 

The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of darunavir or 

1 tablet containing 800 milligram of darunavir) once daily. 

You must take darunavir every day and always in combination with 150 milligram of cobicistat or 

100 milligram of ritonavir and with food. Darunavir cannot work properly without cobicistat or 

ritonavir and food. You must eat a meal or a snack within 30 minutes prior to taking your darunavir 

and cobicistat or ritonavir. The type of food is not important. Even if you feel better, do not stop taking 

darunavir and cobicistat or ritonavir without talking to your doctor. 

 

Instructions for adults 

- Take one 800 milligram tablet at the same time, once a day, every day. 

- Take darunavir always together with 150 milligram of cobicistat or 100 milligram of ritonavir. 

- Take darunavir with food. 

- Swallow the tablet with a drink such as water or milk. 

- Take your other HIV medicines used in combination with darunavir and cobicistat or ritonavir 

as recommended by your doctor. 

 

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this) 

The dose is either: 

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 

800 milligram of darunavir) together with 150 milligram cobicistat or 100 milligram ritonavir 

once daily. 

OR 

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 

600 milligram of darunavir) together with 100 milligram ritonavir twice daily. 

 



178 

 

Please discuss with your doctor which dose is right for you. 

 

Dose for children 3 years of age and above, weighing more than 40 kilograms who have not 

taken antiretroviral medicines before (your child’s doctor will determine this)  

- The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of darunavir or 

1 tablet containing 800 milligram of darunavir) together with 100 milligram ritonavir once 

daily. 

Dose for children 3 years of age and above, weighing more than 40 kilograms who have taken 

antiretroviral medicines before (your child’s doctor will determine this)  

The dose is either: 

- 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 

800 milligram of darunavir) together with 100 milligram ritonavir once daily. 

OR 

- 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing 

600 milligram of darunavir) together with 100 milligram ritonavir twice daily. 

 

Please discuss with your doctor which dose is right for you. 

Instructions for children 3 years of age and above, weighing more than 40 kilograms 

- Take 800 milligram darunavir (2 tablets containing 400 milligram of Darunavir Mylan or 1 

tablet containing 800 milligram of Darunavir Mylan) at the same time, once a day, every day. 

- Take darunavir always together with 100 milligram of ritonavir. 

- Take darunavir with food. 

- Swallow the tablets with a drink such as water or milk. 

- Take your other HIV medicines used in combination with darunavir and ritonavir as 

recommended by your doctor. 

 

If you take more Darunavir Mylan than you should  

Contact your doctor, pharmacist or nurse immediately.  

 

If you forget to take Darunavir Mylan 

If you notice within 12 hours, you must take the tablets immediately. Always take with cobicistat or 

ritonavir and food. If you notice after 12 hours, then skip the intake and take the next doses as usual. 

Do not take a double dose to make up for a forgotten dose. 

 

Do not stop taking Darunavir Mylan without talking to your doctor first  

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking 

Darunavir Mylan. Talk to your doctor first.  

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

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. 

 

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

 

Tell your doctor if you develop any of the following side effects.  

 

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests 

before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check 

your blood tests more often because you have an increased chance of developing liver problems. Talk 

to your doctor about the signs and symptoms of liver problems. These may include yellowing of your 

skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), 



179 

 

nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below 

your ribs.  

 

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to 

moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your 

doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether 

darunavir must be stopped.  

 

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).  

 

Very common side effects (may affect more than 1 in 10 people)  

- diarrhoea.  
 

Common side effects (may affect up to 1 in 10 people)  

- vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence  
- headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of 

strength, difficulty falling asleep.  

 

Uncommon side effects (may affect up to 1 in 100 people)  

- chest pain, changes in electrocardiogram, rapid heart beating  
- decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, 

problems with your balance  

- difficulty breathing, cough, nosebleed, throat irritation  
- inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the 

abdomen, constipation, belching  

- kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of 
urine, sometimes at night  

- urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, 
excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails 

- muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis  
- slowing down of the thyroid gland function. This can be seen in a blood test.  
- high blood pressure, flushing  
- red or dry eyes  
- fever, swelling of lower limbs due to fluids, malaise, irritability, pain  
- symptoms of infection, herpes simplex  
- erectile dysfunction, enlargement of breasts  
- sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive  
 

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

- a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of 
the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, 

kidney or lung]  

- heart attack, slow heart beating, palpitations  
- visual disturbance  
- chills, feeling abnormal  
- a feeling of confusion or disorientation, altered mood, restlessness  
- fainting, epileptic fits, changes or loss of taste  
- mouth sores, vomiting blood, inflamation of the lips, dry lips, coated tongue  
- running nose  
- skin lesions, dry skin  
- stiffness of muscles or joints, joint pain with or without inflammation  
- changes in some values of your blood cells or chemistry. These can be seen in the results of 

blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some 

white blood cells.  

 

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:  



180 

 

- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been 
serious.  

 

Reporting of side effects  

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

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

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Darunavir Mylan 

 

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

 

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle 

after EXP. The expiry date refers to the last day of that month.  

 

For blisters with plastic on one side and aluminium on the other: Do not store above 25°C. 

 

For blisters with aluminium on both sides: This medicine does not require any special storage 

conditions. 

 

For bottles: Once opened, use within 90 days. This medicine does not require any special storage 

conditons. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What Darunavir Mylan contains 

- The active substance is darunavir. Each tablet contains 800 milligram of darunavir.  
- The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone, 

sodium starch glycolate, hypromellose, magnesium stearate. The film-coating contains 

polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol and talc. 

  

What Darunavir Mylan looks like and contents of the pack 

 

Darunavir Mylan 800 mg film-coated tablets are white to off-white, oval shaped, with two curved 

sides, marked with M on one side and DV8 on the other side. 

 

Darunavir Mylan 800 mg film-coated tablets are available in blister packs containing 30 tablets and in 

plastic bottles containing 30, 60 and 90 tablets.  

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder  

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturers 

Mylan Hungary Kft 

H-2900 Komárom, Mylan utca 1 

Hungary 

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


181 

 

 

McDermott Laboratories Limited trading as Gerard Laboratories 

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

Ireland 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1 

Bad Homburg v. d. Hoehe 

Hessen, 61352  

Germany 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

 

Lietuva 

BGP Products UAB  

Tel: +370 5 205 1288 

 

 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 

Danmark 

Mylan Denmark ApS 

Tel: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

 

Deutschland 

Mylan Healthcare GmbH  

Tel: +49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: +31 (0)20 426 3300 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα  

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410  

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 2418 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 



182 

 

France 

Mylan S.A.S 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: +353 (0) 87 1694982  

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

 

Ísland 

Icepharma hf 

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: +421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

 

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB  

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

 

 

United Kingdom 

Generics [UK] Ltd 

Tel: +44 1707 853000 

 

This leaflet was last revised in {MM/YYYY}. 

 

Other sources of information 

 

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

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

 

 

 

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

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