Ritonavir Mylan

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

  



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1. NAME OF THE MEDICINAL PRODUCT 
 

Ritonavir Mylan 100 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each film-coated tablet contains 100 mg of ritonavir. 

 

Excipient with known effect 

Each film-coated tablet contains 87.75 mg of sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Film-coated tablet (tablet). 

 

Yellow, capsule shaped film-coated tablet, approximately 19.1 mm x 10.2 mm, debossed with ‘M163’ 

on one side and plain on the other side. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 

infected patients (adults and children of 2 years of age and older). 

 

4.2 Posology and method of administration 
 

Ritonavir Mylan should be administered by physicians who are experienced in the treatment of HIV 

infection. 

 

Posology 

 

Ritonavir dosed as a pharmacokinetic enhancer 

When ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors the Summary of 

Product Characteristics for the particular protease inhibitor must be consulted. 

 

The following HIV-1 protease inhibitors have been approved for use with ritonavir as a 

pharmacokinetic enhancer at the noted doses. 

 

Adults 

Amprenavir 600 mg twice daily with ritonavir 100 mg twice daily. 

Atazanavir 300 mg once daily with ritonavir 100 mg once daily. 

Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily. 

Lopinavir co-formulated with ritonavir (lopinavir/ritonavir) 400 mg/100 mg or 800 mg/200 mg. 

Saquinavir 1,000 mg twice daily with ritonavir 100 mg twice daily in ART experienced patients. 

Initiate treatment with saquinavir 500 mg twice daily with ritonavir 100 mg twice daily for the first 

7 days, then saquinavir 1,000 mg twice daily with ritonavir 100 mg twice daily in ART-naïve patients. 

Tipranavir 500 mg twice daily with ritonavir 200 mg twice daily. Tipranavir with ritonavir should not 

be used in treatment-naïve patients. 

Darunavir 600 mg twice daily with ritonavir 100 mg twice daily in antiretroviral treatment. 



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(ART) experienced patients. Darunavir 800 mg once daily with ritonavir 100 mg once daily may be 

used in some ART experienced patients. Refer to the darunavir Summary of Product Characteristics 

for further information on once daily dosing in ART experienced patients. 

Darunavir 800 mg once daily with ritonavir 100 mg once daily in ART-naïve patients. 

 

Children and adolescents 

Ritonavir is recommended for children 2 years of age and older. For further dosage recommendations, 

refer to the product information of other Protease Inhibitors approved for co-administration with 

ritonavir. 

 

Special populations 

 

Renal impairment 

As ritonavir is primarily metabolised by the liver, ritonavir may be appropriate for use with caution as 

a pharmacokinetic enhancer in patients with renal insufficiency depending on the specific protease 

inhibitor with which it is co-administered. However, since the renal clearance of ritonavir is 

negligible, the decrease in the total body clearance is not expected in patients with renal impairment. 

For specific dosing information in patients with renal impairment, refer to the Summary of Product 

Characteristics (SPC) of the co-administered protease inhibitor. 

 

Hepatic impairment 

Ritonavir should not be given as a pharmacokinetic enhancer to patients with decompensated liver 

disease, (see section 4.3). In the absence of pharmacokinetic studies in patients with stable severe 

hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when 

ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered PI may 

occur. Specific recommendations for use of ritonavir as a pharmacokinetic enhancer in patients with 

hepatic impairment are dependent on the protease inhibitor with which it is co-administered. The SPC 

of the co-administered PI should be reviewed for specific dosing information in this patient 

population. 

 

Ritonavir dosed as an antiretroviral agent 

 

Adults 

The recommended dose of ritonavir is 600 mg (6 tablets) twice daily (total of 1,200 mg per day) by 

mouth. 

 

Gradually increasing the dose of ritonavir when initiating therapy may help to improve tolerance. 

Treatment should be initiated at 300 mg (3 tablets) twice daily for a period of three days and increased 

by 100 mg (1 tablet) twice daily increments up to 600 mg twice daily over a period of no longer than 

14 days. Patients should not remain on 300 mg twice daily for more than 3 days. 

 

Paediatric population (2 years of age and above) 

The recommended dosage of ritonavir in children is 350 mg/m2 by mouth twice daily and should not 

exceed 600 mg twice daily. Ritonavir should be started at 250 mg/m2 and increased at 2 to 3 day 

intervals by 50 mg/m2 twice daily.  

 

Other pharmaceutical forms/strengths may be more appropriate for administration to this population. 

 

For older children it may be feasible to substitute tablets for the maintenance dose of other 

pharmaceutical forms. 

  



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Dosage conversion from oral solution to tablets for children 

 

Oral solution dose Tablet dose 

175 mg (2.2 ml) twice daily 200 mg in the morning and 200 mg in the evening 

350 mg (4.4 ml) twice daily 400 mg in the morning and 300 mg in the evening 

437.5 mg (5.5 ml) twice daily 500 mg in the morning and 400 mg in the evening 

525 mg (6.6 ml) twice daily 500 mg in the morning and 500 mg in the evening 

 

Ritonavir is not recommended in children below 2 years of age due to lack of data on safety and 

efficacy. 

 

Special populations 

 

Elderly 

Pharmacokinetic data indicated that no dose adjustment is necessary for elderly patients (see section 

5.2). 

 

Renal impairment 

Currently, there are no data specific to this patient population and therefore specific dosage 

recommendations cannot be made. The renal clearance of ritonavir is negligible therefore; a decrease 

in the total body clearance is not expected in patients with renal impairment. Because ritonavir is 

highly protein bound it is unlikely that it will be significantly removed by haemodialysis or peritoneal 

dialysis. 

 

Hepatic impairment 

Ritonavir is principally metabolised and eliminated by the liver. Pharmacokinetic data indicate that no 

dose adjustment is necessary in patients with mild to moderate hepatic impairment (see section 5.2). 

Ritonavir must not be given to patients with severe hepatic impairment (see section 4.3). 

 

Paediatric population 

The safety and efficacy of ritonavir in children aged below 2 years has not been established. Currently 

available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be 

made. 

 

Method of administration 

 

Ritonavir Mylan film-coated tablets are administered orally and should be ingested with food (see 

section 5.2). 

 

Ritonavir Mylan film-coated tablets should be swallowed whole and not chewed, broken or crushed. 

 

4.3 Contraindications 
 

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

 

When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the Summary of Product 

Characteristics of the co-administered protease inhibitor for contraindications. 

 

Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients 

with decompensated liver disease. 

 

In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and 

CYP2D6- mediated biotransformations. The following medicines are contraindicated when used with 

ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to 

inhibit metabolism of the co-administered medicinal product, resulting in increased exposure to the 

co-administered medicinal product and risk of clinically significant adverse effects. 

 



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The enzyme-modulating effect of ritonavir may be dose dependent. For some products, 

contraindications may be more relevant when ritonavir is used as an antiretroviral agent than when 

ritonavir is used as a pharmacokinetic enhancer (e.g. rifabutin and voriconazole): 

 

Medicinal Product Class Medicinal Products within 

Class 

Rationale 

Concomitant medicinal product levels increased or decreased 

α1-Adrenoreceptor 

Antagonist 

Alfuzosin Increased plasma 

concentrations of alfuzosin 

which may lead to severe 

hypotension (see section 4.5). 

Analgesics Pethidine, piroxicam, 

propoxyphene 

Increased plasma 

concentrations of norpethidine, 

piroxicam and propoxyphene. 

Thereby, increasing the risk of 

serious respiratory depression 

or haematologic abnormalities, 

or other serious adverse effects 

from these agents. 

Antianginal Ranolazine Increased plasma 

concentrations of ranolazine 

which may increase the 

potential for serious and/or 

life-threatening reactions (see 

section 4.5). 

Anticancer Neratinib Increased plasma 

concentrations of neratinib 

which may increase the 

potential for serious and/or 

life-threatening reactions 

including hepatotoxicity (see 

section 4.5). 

Venetoclax Increased plasma 

concentrations of venetoclax. 

Increased risk of tumor lysis 

syndrome at the dose initiation 

and during the dose-titration 

phase (see section 4.5). 

Antiarrhythmics Amiodarone, bepridil, 

dronedarone, encainide, 

flecainide, propafenone, 

quinidine 

Increased plasma 

concentrations of amiodarone, 

bepridil, dronedarone, 

encainide, flecainide, 

propafenone, quinidine. 

Thereby, increasing the risk of 

arrhythmias or other serious 

adverse effects from these 

agents. 

Antibiotic Fusidic acid Increased plasma 

concentrations of fusidic acid 

and ritonavir. 

Antifungal Voriconazole Concomitant use of ritonavir 

(400 mg twice daily and more) 

and voriconazole is 

contraindicated due to a 

reduction in voriconazole 

plasma concentrations and 



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possible loss of effect (see 

section 4.5). 

Antihistamines Astemizole, terfenadine Increased plasma 

concentrations of astemizole 

and terfenadine. Thereby, 

increasing the risk of serious 

arrhythmias from these agents. 

Anti-gout Colchicine Potential for serious and/or 

life-threatening reactions in 

patients with renal and/or 

hepatic impairment (see 

sections 4.4 and 4.5). 

Antimycobacterial Rifabutin Concomitant use of ritonavir 

(500 mg twice daily) dosed as 

an antiretroviral agent and 

rifabutin due to an increase of 

rifabutin serum concentrations 

and risk of adverse reactions 

including uveitis (see section 

4.4). 

Recommendations regarding 

use of ritonavir dosed as a 

pharmacokinetic enhancer with 

rifabutin are noted in section 

4.5. 

Antipsychotics/ 

Neuroleptics 

Lurasidone Increased plasma 

concentrations of lurasidone 

which may increase the 

potential for serious and/or 

life-threatening reactions (see 

section 4.5). 

 Clozapine, pimozide Increased plasma 

concentrations of clozapine 

and pimozide. Thereby, 

increasing the risk of serious 

haematologic abnormalities, or 

other serious adverse effects 

from these agents. 

 Quetiapine Increased plasma 

concentrations of quetiapine 

which may lead to coma. The 

concomitant administration 

with quetiapine is 

contraindicated (see section 

4.5). 

Ergot derivatives Dihydroergotamine, 

ergonovine, ergotamine, 

methylergonovine 

Increased plasma 

concentrations of ergot 

derivatives leading to acute 

ergot toxicity, including 

vasospasm and ischaemia. 

GI motility agent Cisapride Increased plasma 

concentrations of cisapride. 

Thereby, increasing the risk of 

serious arrhythmias from this 

agent. 

 

Lipid-modifying agents 

 

 

 

 



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HMG Co-A reductase 

inhibitors 

 

 

 

 

 

Microsomal triglyceride 

transfer protein (MTTP) 

inhibitor 

 

Lovastatin, simvastatin 

 

 

 

 

 

 

Lomitapide 

 

Increased plasma 

concentrations of lovastatin 

and simvastatin; thereby, 

increasing the risk of myopathy 

including rhabdomyolysis (see 

section 4.5). 

 

Increased plasma 

concentrations of lomitapide 

(see section 4.5). 

PDE5 inhibitor Avanafil Increased plasma 

concentrations of avanafil (see 

sections 4.4. and 4.5). 

 Sildenafil Contraindicated when used for 

the treatment of pulmonary 

arterial hypertension (PAH) 

only. 

Increased plasma 

concentrations of sildenafil. 

Thereby, increasing the 

potential for 

sildenafil-associated adverse 

events (which include 

hypotension and syncope). See 

section 4.4 and section 4.5 for 

co-administration of sildenafil 

in patients with erectile 

dysfunction. 

 Vardenafil Increased plasma 

concentrations of vardenafil 

(see sections 4.4. and 4.5). 

Sedatives/hypnotics Clorazepate, diazepam, 

estazolam, flurazepam, oral 

midazolam and triazolam 

Increased plasma 

concentrations of clorazepate, 

diazepam, estazolam, 

flurazepam, oral midazolam 

and triazolam. Thereby, 

increasing the risk of extreme 

sedation and respiratory 

depression from these agents. 

(For caution on parenterally 

administered midazolam, see 

section 4.5.). 

Ritonavir medicinal product level decreased 

Herbal preparation St John’s wort Herbal preparations containing 

St John’s wort (Hypericum 

perforatum) due to the risk of 

decreased plasma 

concentrations and reduced 

clinical effects of ritonavir (see 

section 4.5). 

 

4.4 Special warnings and precautions for use 
 

Ritonavir is not a cure for HIV-1 infection or AIDS. Patients receiving ritonavir or any other 

antiretroviral therapy may continue to develop opportunistic infections and other complications of 

HIV-1 infection. 



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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. 

 

When ritonavir is used as a pharmacokinetic enhancer with other PIs, full details on the warnings and 

precautions relevant to that particular PI should be considered, therefore the Summary of Product 

Characteristics for the particular PI must be consulted. 

 

Ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer 

 

Patients with chronic diarrhoea or malabsorption 

 

Extra monitoring is recommended when diarrhoea occurs. The relatively high frequency of diarrhoea 

during treatment with ritonavir may compromise the absorption and efficacy (due to decreased 

compliance) of ritonavir or other concurrent medicinal products. Serious persistent vomiting and/or 

diarrhoea associated with ritonavir use might also compromise renal function. It is advisable to 

monitor renal function in patients with renal function impairment. 

 

Haemophilia 

 

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

haemarthroses, in haemophiliac patients type A and B treated with protease inhibitors. In some 

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

protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal 

relationship has been evoked, 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. 

 

Pancreatitis 

 

Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or 

abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of 

pancreatitis should occur. Patients who exhibit these signs or symptoms should be evaluated and 

ritonavir therapy should be discontinued if a diagnosis of pancreatitis is made (see section 4.8). 

 

Immune reconstitution inflammatory syndrome 

 

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

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

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

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

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

and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and 

treatment instituted when necessary. 

 

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

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

can occur many months after initiation of treatment. 

Liver disease 



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Ritonavir should not be given to patients with decompensated liver disease (see section 4.2). Patients 

with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased 

risk for severe and potentially fatal hepatic adverse reactions. In case of concomitant antiviral therapy 

for hepatitis B or C, please refer to the relevant product information for these medicinal products. 

 

Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased 

frequency of liver function abnormalities during combination antiretroviral therapy and should be 

monitored according to standard practice. If there is evidence of worsening liver disease in such 

patients, interruption or discontinuation of treatment must be considered. 

 

Renal disease 

 

Since the renal clearance of ritonavir is negligible, the decrease in the total body clearance is not 

expected in patients with renal impairment (see also section 4.2). 

 

Renal failure, renal impairment, elevated creatinine, hypophosphataemia and proximal tubulopathy 

(including Fanconi syndrome) have been reported with the use of tenofovir disoproxil fumarate (DF) 

in clinical practice (see section 4.8). 

 

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 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. 

 

PR interval prolongation 

 

Ritonavir has been shown to cause modest asymptomatic prolongation of the PR interval in some 

healthy adult subjects. Rare reports of 2nd or 3rd degree atrioventricular block in patients with 

underlying structural heart disease and pre-existing conduction system abnormalities or in patients 

receiving medicinal products known to prolong the PR interval (such as verapamil or atazanavir) have 

been reported in patients receiving ritonavir. Ritonavir should be used with caution in such patients 

(see section 5.1). 

 

Interactions with other medicinal products 

 

Ritonavir dosed as an antiretroviral agent 

The following warnings and precautions should be considered when ritonavir is used as an 

antiretroviral agent. When ritonavir is used as a pharmacokinetic enhancer at the 100 mg and 200 mg 

level it cannot be assumed that the following warnings and precautions will also apply. When ritonavir 

is used as a pharmacokinetic enhancer, full details on the warnings and precautions relevant to that 

particular PI must be considered, therefore the Summary of Product Characteristics, section 4.4, for 

the particular PI must be consulted to determine if the information below is applicable. 

 

PDE5 inhibitors 

Particular caution should be used when prescribing sildenafil or tadalafil for the treatment of erectile 

dysfunction in patients receiving ritonavir. Co-administration of ritonavir with these medicinal 

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

reactions such as hypotension and prolonged erection (see section 4.5). Concomitant use of avanafil or 

vardenafil with ritonavir is contraindicated (see section 4.3). Concomitant use of sildenafil with 

ritonavir is contraindicated in pulmonary arterial hypertension patients (see section 4.3). 

 

HMG-CoA reductase inhibitors 



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The HMG-CoA reductase inhibitors simvastatin and lovastatin are highly dependent on CYP3A for 

metabolism, thus concomitant use of ritonavir with simvastatin or lovastatin is not recommended due 

to an increased risk of myopathy including rhabdomyolysis. Caution must also be exercised and 

reduced doses should be considered if ritonavir is used concurrently with atorvastatin, which is 

metabolised to a lesser extent by CYP3A. While rosuvastatin elimination is not dependent on CYP3A, 

an elevation of rosuvastatin exposure has been reported with ritonavir co-administration. The 

mechanism of this interaction is not clear, but may be the result of transporter inhibition. When used 

with ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent, the lowest doses of 

atorvastatin or rosuvastatin should be administered. The metabolism of pravastatin and fluvastatin is 

not dependent of CYP3A, and interactions are not expected with ritonavir. If treatment with an HMG-

CoA reductase inhibitor is indicated, pravastatin or fluvastatin is recommended (see section 4.5). 

 

Colchicine 

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

strong inhibitors of CYP3A like ritonavir (see sections 4.3 and 4.5). 

 

Digoxin 

Particular caution should be used when prescribing ritonavir in patients taking digoxin since 

co-administration of ritonavir with digoxin is expected to increase digoxin levels. The increased 

digoxin levels may lessen over time (see section 4.5). 

 

In patients who are already taking digoxin when ritonavir is introduced, the digoxin dose should be 

reduced to one-half of the patients’ normal dose and patients need to be followed more closely than 

usual for several weeks after initiating co-administration of ritonavir and digoxin. 

 

In patients who are already taking ritonavir when digoxin is introduced, digoxin should be introduced 

more gradually than usual. Digoxin levels should be monitored more intensively than usual during this 

period, with dose adjustments made, as necessary, based on clinical, electrocardiographic and digoxin 

level findings. 

 

Ethinylestradiol 

Barrier or other non-hormonal methods of contraception should be considered when administering 

ritonavir at therapeutic or low doses as ritonavir is likely to reduce the effect and change the uterine 

bleeding profile when co-administered with estradiol-containing contraceptives. 

 

Glucocorticoids 

Concomitant use of ritonavir and fluticasone or other glucocorticoids that are metabolised by CYP3A4 

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

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

 

Trazodone 

Particular caution should be used when prescribing ritonavir in patients using trazodone. Trazodone is 

a CYP3A4 substrate and co-administration of ritonavir is expected to increase trazodone levels. 

Adverse reactions of nausea, dizziness, hypotension and syncope have been observed in single dose 

interaction studies in healthy volunteers (see section 4.5). 

 

Rivaroxaban 

It is not recommended to use ritonavir in patients receiving rivaroxaban, due to the risk of increased 

bleeding (see section 4.5). 

 

Riociguat 

The concomitant use of ritonavir is not recommended due to potential increase in riociguat exposure 

(see section 4.5). 

 

Vorapaxar 

The concomitant use of ritonavir is not recommended due to potential increase in vorapaxar exposure 

(see section 4.5). 



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Bedaquiline 

Strong CYP3A4 inhibitors such as protease inhibitors may increase bedaquiline exposure which could 

potentially increase the risk of bedaquiline-related adverse reactions. Therefore, combination of 

bedaquiline with ritonavir should be avoided. However, if the benefit outweighs the risk, 

co-administration of bedaquiline with ritonavir must be done with caution. More frequent 

electrocardiogram monitoring and monitoring of transaminases is recommended (see section 4.5 and 

refer to the bedaquiline Summary of Product Characteristics). 

 

Delamanid 

Co-administration of delamanid with a strong inhibitor of CYP3A (ritonavir) may increase exposure to 

delamanid metabolite, which has been associated with QTc prolongation. Therefore, if 

co-administration of delamanid with ritonavir is considered necessary, very frequent ECG monitoring 

throughout the full delamanid treatment period is recommended (see section 4.5 and refer to the 

delamanid Summary of Product Characteristics). 

 

Ritonavir dosed as a pharmacokinetic enhancer 

The interaction profiles of HIV-protease inhibitors, co-administered with low dose ritonavir, are 

dependent on the specific co-administered protease inhibitor. 

 

For a description of the mechanisms and potential mechanisms contributing to the interaction profile 

of the PIs, see section 4.5. Please also review the Summary of Product Characteristics for the 

particular boosted PI. 

 

Saquinavir 

Doses of ritonavir higher than 100 mg twice daily should not be used. Higher doses of ritonavir have 

been shown to be associated with an increased incidence of adverse reactions. Co-administration of 

saquinavir and ritonavir has led to severe adverse reactions, mainly diabetic ketoacidosis and liver 

disorders, especially in patients with pre-existing liver disease. 

 

Saquinavir/ritonavir should not be given together with rifampicin, due to the risk of severe 

hepatotoxicity (presenting as increased hepatic transaminases) if the three medicines are given 

together (see section 4.5). 

 

Tipranavir 

Co-administration of tipranavir with 200 mg of ritonavir has been associated with reports of clinical 

hepatitis and hepatic decompensation including some fatalities. Extra vigilance is warranted in patients 

with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of 

hepatotoxicity. 

 

Doses of ritonavir lower than 200 mg twice daily should not be used as they might alter the efficacy 

profile of the combination. 

 

Fosamprenavir 

Co-administration of fosamprenavir with ritonavir in doses greater than 100 mg twice daily has not 

been clinically evaluated. The use of higher ritonavir doses might alter the safety profile of the 

combination and therefore is not recommended. 

 

Atazanavir 

Co-administration of atazanavir with ritonavir at doses greater than 100 mg once daily has not been 

clinically evaluated. The use of higher ritonavir doses may alter the safety profile of atazanavir 

(cardiac effects, hyperbilirubinemia) and therefore is not recommended. Only when atazanavir with 

ritonavir is co-administered with efavirenz, a dose increase of ritonavir to 200 mg once daily could be 

considered. In this instance, close clinical monitoring is warranted. Refer to the Summary of Product 

Characteristics for atazanavir for further details. 

 

Excipients 



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This medicinal product contains 87.75 mg sodium per tablet, equivalent to 4.4% of the WHO 

recommended maximum daily intake of 2 g sodium for an adult.  

 

The maximum daily dose of this product is equivalent to 53% of the WHO recommended maximum 

daily intake for sodium. 

 

Ritonavir is considered high in sodium. This should be particularly taken into account for those on a 

low sodium diet. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent 

 

Ritonavir has a high affinity for several cytochrome P450 (CYP) isoforms and may inhibit oxidation 

with the following ranked order: CYP3A4 > CYP2D6. Co-administration of ritonavir and medicinal 

products primarily metabolised by CYP3A may result in increased plasma concentrations of the other 

medicinal product, which could increase or prolong its therapeutic and adverse effects. For selected 

medicinal products (e.g. alprazolam) the inhibitory effects of ritonavir on CYP3A4 may decrease over 

time. Ritonavir also has a high affinity for P-glycoprotein and may inhibit this transporter. The 

inhibitory effect of ritonavir (with or without other protease inhibitors) on P-gp activity may decrease 

over time (e.g. digoxin and fexofenadine-see table “Ritonavir effects on non-antiretroviral medicinal 

products” below). Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, 

CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products 

metabolised by these pathways, and may result in decreased systemic exposure to such medicinal 

products, which could decease or shorten their therapeutic effect. 

 

Important information regarding medicinal product interactions when ritonavir is used as a 

pharmacokinetic enhancer is also contained in the Summary of Product Characteristics of the 

co-administered protease inhibitor. 

 

Medicinal products that affect ritonavir levels 

 

Serum levels of ritonavir can be reduced by concomitant use of herbal preparations containing St 

John’s wort (Hypericum perforatum). This is due to the induction of medicinal product metabolising 

enzymes by St John’s wort. Herbal preparations containing St John’s wort must not be used in 

combination with ritonavir. If a patient is already taking St John’s wort, St John’s wort should be 

stopped and if possible check viral levels. Ritonavir levels may increase on stopping St John’s wort. 

The dose of ritonavir may need adjusting. The inducing effect may persist for at least 2 weeks after 

cessation of treatment with St John’s wort (see section 4.3). 

 

Serum levels of ritonavir may be affected by select co-administered medicinal products (e.g. 

delavirdine, efavirenz, phenytoin and rifampicin). These interactions are noted in the medicinal 

product interaction tables below. 

 

Medicinal products that are affected by the use of ritonavir 

 

Interactions between ritonavir and protease inhibitors, antiretroviral agents other than protease 

inhibitors and other non-antiretroviral medicinal products are listed in the tables below. This list is not 

intended to be inclusive or comprehensive.  Individual SmPCs should be consulted. 

 

Medicinal product interactions – Ritonavir with protease inhibitors 

 
Co-administered 

Medicinal 

Product 

Dose of 

Co-administered 

Medicinal 

Product (mg) 

Dose of 

Ritonavir 

(mg) 

Medicinal 

Product 

Assessed 

AUC Cmin 

Amprenavir 600 q12 h 100 q12 h Amprenavir2 ↑ 64% ↑ 5 fold 



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Co-administered 

Medicinal 

Product 

Dose of 

Co-administered 

Medicinal 

Product (mg) 

Dose of 

Ritonavir 

(mg) 

Medicinal 

Product 

Assessed 

AUC Cmin 

 Ritonavir increases the serum levels of amprenavir as a result of CYP3A4 inhibition. 

Clinical trials confirmed the safety and efficacy of 600 mg amprenavir twice daily with 

ritonavir 100 mg twice daily. Ritonavir oral solution should not be co-administered 

with amprenavir oral solution to children due to the risk of toxicity from excipients in 

the two formulations. For further information, physicians should refer to the Summary 

of Product Characteristics for amprenavir. 

Atazanavir 300 q24 h 100 q24 h Atazanavir 

Atazanavir1 

↑ 86% 

↑ 2 fold 

↑ 11 fold 

↑ 3-7 fold 

 Ritonavir increases the serum levels of atazanavir as a result of CYP3A4 inhibition. 

Clinical trials confirmed the safety and efficacy of 300 mg atazanavir once daily with 

ritonavir 100 mg once daily in treatment experienced patients. For further information, 

physicians should refer to the Summary of Product Characteristics for atazanavir. 

Darunavir 600, single 100 q12 h Darunavir ↑ 14 fold  

 Ritonavir increases the serum levels of darunavir as a result of CYP3A inhibition. 

Darunavir must be given with ritonavir to ensure its therapeutic effect. Ritonavir doses 

higher than 100 mg twice daily have not been studied with darunavir. For further 

information, refer to the Summary of Product Characteristics for darunavir. 

Fosamprenavir 700 q12 h 100 q12 h Amprenavir ↑ 2.4 fold ↑ 11 fold 

 Ritonavir increases the serum levels of amprenavir (from fosamprenavir) as a result of 

CYP3A4 inhibition. Fosamprenavir must be given with ritonavir to ensure its 

therapeutic effect. Clinical trials confirmed the safety and efficacy of fosamprenavir 

700 mg twice daily with ritonavir 100 mg twice daily. Ritonavir doses higher than 

100 mg twice daily have not been studied with fosamprenavir. For further information, 

physicians should refer to the Summary of Product Characteristics for fosamprenavir. 

Indinavir 800 q12 h 100 q12 h Indinavir3 

Ritonavir 

↑ 178% 

↑ 72% 

ND 

ND 

 400 q12 h 400 q12 h Indinavir3 

Ritonavir 

↔ 

↔ 

↑ 4 fold 

↔ 

 Ritonavir increases the serum levels of indinavir as a result of CYP3A4 inhibition. 

Appropriate doses for this combination, with respect to efficacy and safety, have not 

been established. 

Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with 

doses higher than 100 mg twice daily. In cases of co-administration of ritonavir 

(100 mg twice daily) and indinavir (800 mg twice daily) caution is warranted as the 

risk of nephrolithiasis may be increased. 

Nelfinavir 1,250 q12 h 

750, single 

100 q12 h 

500 q12 h 

Nelfinavir 

Nelfinavir 

Ritonavir 

↑ 20 to 39% 

↑ 152% 

↔ 

ND 

ND 

↔ 

 Ritonavir increases the serum levels of nelfinavir as a result of CYP3A4 inhibition. 

Appropriate doses for this combination, with respect to efficacy and safety, have not 

been established. 

Minimal benefit of ritonavir-mediated pharmacokinetic enhancement is achieved with 

doses higher than 100 mg twice daily. 

Saquinavir 1,000 q12 h 100 q12 h Saquinavir4 

Ritonavir 

↑ 15-fold 

↔ 

↑ 5-fold 

↔ 

 400 q12 h 400 q12 h Saquinavir4 

Ritonavir 

↑ 17-fold 

↔ 

ND 

↔ 

 Ritonavir increases the serum levels of saquinavir as a result of CYP3A4 inhibition. 

Saquinavir should only be given in combination with ritonavir. Ritonavir 100 mg twice 

daily with saquinavir 1,000 mg twice daily provides saquinavir systemic exposure over 

24 hours similar to or greater than those achieved with saquinavir 1,200 mg three times 

daily without ritonavir. 

 

In a clinical study investigating the interaction of rifampicin 600 mg once daily and 

saquinavir 1,000 mg with ritonavir 100 mg twice daily in healthy volunteers, severe 

hepatocellular toxicity with transaminase elevations up to > 20-fold the upper limit of 

normal after 1 to 5 days of co-administration was noted. Due to the risk of severe 

hepatotoxicity, saquinavir/ritonavir should not be given together with rifampicin. 

 



14 

Co-administered 

Medicinal 

Product 

Dose of 

Co-administered 

Medicinal 

Product (mg) 

Dose of 

Ritonavir 

(mg) 

Medicinal 

Product 

Assessed 

AUC Cmin 

For further information, physicians should refer to the Summary of Product 

Characteristics for saquinavir. 

Tipranavir 500 q12 h 200 q12 h Tipranavir 

Ritonavir 

↑ 11 fold 

↓ 40% 

↑ 29 fold 

ND 

 Ritonavir increases the serum levels of tipranavir as a result of CYP3A inhibition. 

Tipranavir must be given with low dose ritonavir to ensure its therapeutic effect. Doses 

of ritonavir less than 200 mg twice daily should not be used with tipranavir as they 

might alter the efficacy of the combination. For further information, physicians should 

refer to the Summary of Product Characteristics for tipranavir. 

 ND: Not determined. 
1 Based on cross-study comparison to 400 mg atazanavir once daily alone. 
2 Based on cross-study comparison to 1,200 mg amprenavir twice daily alone. 
3 Based on cross-study comparison to 800 mg indinavir three times daily alone. 
4 Based on cross-study comparison to 600 mg saquinavir three times daily alone. 

 

 

Medicinal product interactions – Ritonavir with antiretroviral agents other than protease 

inhibitors 

 
Co-administered 

Medicinal 

Product 

Dose of 

Co-administered 

Medicinal 

Product (mg) 

Dose of 

Ritonavir 

(mg) 

Medicinal 

Product 

Assessed 

AUC Cmin 

Didanosine 200 q12 h 600 q12 h 2 h 

later 

Didanosine ↓ 13% ↔ 

 As ritonavir is recommended to be taken with food and didanosine should be taken on an 

empty stomach, dosing should be separated by 2.5 h. Dose alterations should not be 

necessary. 

Delavirdine 400 q8 h 600 q12 h Delavirdine1 

Ritonavir 

↔ 

↑ 50% 

↔ 

↑ 75% 

 Based on comparison to historical data, the pharmacokinetics of delavirdine did not 

appear to be affected by ritonavir. When used in combination with delavirdine, dose 

reduction of ritonavir may be considered. 

Efavirenz 600 q24 h 500 q12 h Efavirenz 

Ritonavir 

↑ 21% 

↑ 17% 

 

 A higher frequency of adverse reactions (e.g., dizziness, nausea, paraesthesia) and 

laboratory abnormalities (elevated liver enzymes) have been observed when efavirenz is 

co-administered with ritonavir dosed as an antiretroviral agent. 

Maraviroc 100 q12 h 100 q12 h Maraviroc ↑ 161% ↑ 28% 

 Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. 

Maraviroc may be given with ritonavir to increase the maraviroc exposure. For further 

information, refer to the Summary of Product Characteristics for maraviroc. 

Nevirapine 200 q12 h 600 q12 h Nevirapine 

Ritonavir 

↔ 

↔ 

↔ 

↔ 

 Co-administration of ritonavir with nevirapine does not lead to clinically relevant 

changes in the pharmacokinetics of either nevirapine or ritonavir. 

Raltegravir 400 single 100 q12 h Raltegravir ↓ 16% ↓ 1% 

 Co-administration of ritonavir and raltegravir results in a minor reduction in raltegravir 

levels. 

Zidovudine 200 q8 h 300 q6 h Zidovudine ↓ 25% ND 

 Ritonavir may induce the glucuronidation of zidovudine, resulting in slightly decreased 

levels of zidovudine. Dose alterations should not be necessary. 

 ND: Not determined 
1 Based on parallel group comparison. 

 

 

  



15 

Ritonavir effects on non-antiretroviral co-administered medicinal products 

 
Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

Alpha1-Adrenoreceptor antagonist     

Alfuzosin Ritonavir co-administration is likely to result in increased plasma 

concentrations of alfuzosin and is therefore contraindicated (see 

section 4.3). 

 

Amphetamine derivatives     

Amphetamine Ritonavir dosed as an antiretroviral agent is likely to inhibit 

CYP2D6 and as a result is expected to increase concentrations of 

amphetamine and its derivatives. Careful monitoring of therapeutic 

and adverse effects is recommended when these medicines are 

concomitantly administered with antiretroviral doses of ritonavir 

(see section 4.4). 

 

Analgesics     

Buprenorphine 16 q24 h 100 q12 h ↑ 57% ↑ 77% 

Norbuprenorphine   ↑ 33% ↑ 108% 

Glucuronide metabolites   ↔ ↔ 

 The increases of plasma levels of buprenorphine and its active 

metabolite did not lead to clinically significant pharmacodynamic 

changes in a population of opioid tolerant patients. Adjustment to 

the dose of buprenorphine or ritonavir may therefore not be 

necessary when the two are dosed together. When ritonavir is used 

in combination with another protease inhibitor and buprenorphine, 

the SPC of the co-administered protease inhibitor should be 

reviewed for specific dosing information. 

 

Pethidine, piroxicam, propoxyphene Ritonavir co-administration is likely to result in increased plasma 

concentrations of pethidine, piroxicam, and propoxyphene and is 

therefore contraindicated (see section 4.3). 

 

Fentanyl Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A4 and as a result is expected to 

increase the plasma concentrations of fentanyl. Careful monitoring 

of therapeutic and adverse effects (including respiratory depression) 

is recommended when fentanyl is concomitantly administered with 

ritonavir. 

 

Methadone1 5, single dose 500 q12 h, ↓ 36% ↓ 38% 

 Increased methadone dose may be necessary when concomitantly 

administered with ritonavir dosed as an antiretroviral agent or as a 

pharmacokinetic enhancer due to induction of glucuronidation. 

Dose adjustment should be considered based on the patient’s 

clinical response to methadone therapy. 

 

Morphine Morphine levels may be decreased due to induction of 

glucuronidation by co-administered ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer. 

Antianginal  

Ranolazine Due to CYP3A inhibition by ritonavir, concentrations of ranolazine are 
expected to increase. The concomitant administration with ranolazine is 

contraindicated (see section 4.3). 

Antiarrhythmics     

Amiodarone, bepridil, dronedarone, 

encainide, flecainide, propafenone, 

quinidine 

Ritonavir, co-administration is likely to result in increased plasma 

concentrations of amiodarone, bepridil, dronedarone, encainide, 



16 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

flecainide, propafenone, and quinidine and is therefore 

contraindicated (see section 4.3).  

 

Digoxin 0.5 single IV 

dose 

300 q12 h, 

3 days 

↑ 86% ND 

 0.4 single oral 

dose 

200 q12 h, 

13 days 

↑ 22% ↔ 

 This interaction may be due to modification of P-glycoprotein 

mediated digoxin efflux by ritonavir dosed as an antiretroviral agent 

or as a pharmacokinetic enhancer. Increased digoxin levels 

observed in patients receiving ritonavir may lessen over time as 

induction develops (see section 4.4). 

 

Antiasthmatic     

Theophylline1 3 mg/kg q8 h 500 q12 h ↓ 43% ↓ 32% 

 An increased dose of theophyline may be required when 

co-administered with ritonavir, due to induction of CYP1A2. 

 

Anticancer agents     

Afatinib 20 mg, single 

dose 

200 q12 h/1 h 

before 

↑ 48% ↑ 39% 

 40 mg, single 

dose 

200 q12 h/co-

administered 

↑ 19% ↑ 4% 

 40 mg, single 

dose 

200 q12 h/6 h 

after 

↑ 11% ↑ 5% 

 Serum concentrations may be increased due to Breast Cancer 

Resistance Protein (BCRP) and acute P-gp inhibition by ritonavir. 

The extent of increase in AUC and Cmax depends on the timing of 

ritonavir administration. Caution should be exercised in 

administering afatinib with ritonavir (refer to the afatinib SmPC). 

Monitor for ADRs related to afatinib. 

 

Abemaciclib Serum concentrations may be increased due to CYP3A4 inhibition 

by ritonavir. 

 

Co-administration of abemaciclib and ritonavir should be avoided.  

If this co-administration is judged unavoidable, refer to the 

abemaciclib SmPC for dosage adjustment recommendations.  

Monitor for ADRs related to abemaciclib. 

 

Apalutamide Apalutamide is a moderate to strong CYP3A4 inducer and this may 

lead to a decreased exposure of ritonavir and potential loss of 

virologic response.  In addition, serum concentrations may be 

increased when co-administered with ritonavir resulting in the 

potential for serious adverse events including seizure.   

 

Concomitant use of ritonavir with apalutamide is not recommended. 

 

Ceritinib Serum concentrations may be increased due to CYP3A and P-gp 

inhibition by ritonavir. Caution should be exercised in 

administering ceritinib with ritonavir. Refer to the ceritinib SmPC 

for dosage adjustment recommendations. Monitor for ADRs related 

to ceritinib. 

 

Dasatinib, nilotinib, vincristine, 

vinblastine 

Serum concentrations may be increased when co-administered with 

ritonavir resulting in the potential for increased incidence of adverse 

reactions. 

 



17 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

Encorafenib Serum concentrations may be increased when co-administered with 

ritonavir which may increase the risk of toxicity, including the risk 

of serious adverse events such as QT interval prolongation.  

Co-administration of encorafenib and ritonavir should be avoided.  

If the benefit is considered to outweigh the risk and ritonavir must 

be used, patients should be carefully monitored for safety. 

 

Ibrutinib Serum concentrations of ibrutinib may be increased due to CYP3A 

inhibition by ritonavir, resulting in increased risk for toxicity 

including risk of tumor lysis syndrome. Co-administration of 

ibrutinib and ritonavir should be avoided. If the benefit is 

considered to outweigh the risk and ritonavir must be used, reduce 

the ibrutinib dose to 140 mg and monitor patient closely for 

toxicity. 

 

Neratinib Serum concentrations may be increased due to CYP3A4 inhibition 

by ritonavir. 

 

Concomitant use of neratinib with ritonavir is contraindicated due 

to serious and/or life threatening potential reactions including 

hepatotoxicity (see section 4.3). 

 
Venetoclax Serum concentrations may be increased due to CYP3A inhibition by 

ritonavir, resulting in increased risk of tumour lysis syndrome at the 

dose initiation and during the ramp-up phase (see section 4.3 and refer 

to the venetoclax SmPC). 

 

For patients who have completed the ramp-up phase and are on a steady 

daily dose of venetoclax, reduce the venetoclax dose by at least 75% 

when used with strong CYP3A inhibitors (refer to the venetoclax 

SmPC for dosing instructions). 

Anticoagulants     

Rivaroxaban 10, single dose 600 q12 h ↑ 153% ↑ 55% 

 Inhibition of CYP3A and P-gp lead to increased plasma levels and 

pharmacodynamic effects of rivaroxaban which may lead to an 

increased bleeding risk. Therefore, the use of ritonavir is not 

recommended in patients receiving rivaroxaban. 

 

Vorapaxar Serum concentrations may be increased due to CYP3A inhibition 

by ritonavir. The co-administration of vorapaxar with ritonavir is 

not recommended (see section 4.4 and refer to the vorapaxar 

SmPC). 

 

Warfarin 5, single dose 400 q12 h   

S-Warfarin   ↑ 9% ↓ 9% 

R-Warfarin   ↑ 33% ↔ 

 Induction of CYP1A2 and CYP2C9 lead to decreased levels of 

R-warfarin while little pharmacokinetic effect is noted on 

S-warfarin when co-administered with ritonavir. Decreased 

R-warfarin levels may lead to reduced anticoagulation, therefore it 

is recommended that anticoagulation parameters are monitored 

when warfarin is co-administered with ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer. 

 

Anticonvulsants     

Carbamazepine Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A4 and as a result is expected to 

increase the plasma concentrations of carbamazepine. Careful 



18 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

monitoring of therapeutic and adverse effects is recommended when 

carbamazepine is concomitantly administered with ritonavir. 

 

Divalproex, lamotrigine, phenytoin Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent induces oxidation by CYP2C9 and 

glucuronidation and as a result is expected to decrease the plasma 

concentrations of anticonvulsants. 

Careful monitoring of serum levels or therapeutic effects is 

recommended when these medicines are concomitantly 

administered with ritonavir. Phenytoin may decrease serum levels 

of ritonavir. 

 

Antidepressants     

Amitriptyline, fluoxetine, 

imipramine, nortriptyline, 

paroxetine, sertraline 

Ritonavir dosed as an antiretroviral agent is likely to inhibit 

CYP2D6 and as a result is expected to increase concentrations of 

imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or 

sertraline. Careful monitoring of therapeutic and adverse effects is 

recommended when these medicines are concomitantly 

administered with antiretroviral doses of ritonavir (see section 4.4). 

 

Desipramine 100, single oral 

dose 

500 q12 h ↑ 145% ↑ 22% 

 The AUC and Cmax of the 2-hydroxy metabolite were decreased 

15 and 67%, respectively. Dosage reduction of desipramine is 

recommended when co-administered with ritonavir dosed as an 

antiretroviral agent. 

 

Trazodone 50, single dose 200 q12 h ↑ 2.4-fold ↑ 34% 

 An increase in the incidence in trazodone-related adverse reactions 

was noted when co-administered with ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer. If trazodone 

is co-administered with ritonavir, the combination should be used 

with caution, initiating trazodone at the lowest dosage and 

monitoring for clinical response and tolerability. 

 

Anti-gout treatments     

Colchicine Concentrations of colchicine are expected to increase when 

co-administered with ritonavir. 

Life-threatening and fatal drug interactions have been reported in 

patients treated with colchicine and ritonavir (CYP3A4 and P-gp 

inhibition) in patients with renal and/or hepatic impairment (see 

sections 4.3 and 4.4). Refer to the colchicine prescribing 

information. 

 

Antihistamines     

Astemizole, terfenadine Ritonavir co-administration is likely to result in increased plasma 

concentrations of astemizole and terfenadine and is therefore 

contraindicated (see section 4.3). 

 

Fexofenadine Ritonavir may modify P-glycoprotein mediated fexofenadine efflux 

when dosed as an antiretroviral agent or as a pharmacokinetic 

enhancer resulting in increased concentrations of fexofenadine. 

Increased fexofenadine levels may lessen over time as induction 

develops. 

 

Loratadine Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A and as a result is expected to 



19 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

increase the plasma concentrations of loratadine. Careful 

monitoring of therapeutic and adverse effects is recommended when 

loratadine is concomitantly administered with ritonavir. 

 

Anti-infectives     

Fusidic acid Ritonavir co-administration is likely to result in increased plasma 

concentrations of both fusidic acid and ritonavir and is therefore 

contraindicated (see section 4.3). 

 

Rifabutin1 150 daily 500 q12 h ↑ 4-fold ↑ 2.5-fold 

 

25-O-desacetyl rifabutin metabolite   ↑ 38-fold ↑ 16-fold 

 Due to the large increase in rifabutin AUC, the concomitant use of 

rifabutin with ritonavir dosed as an antiretroviral agent is 

contraindicated (see section 4.3). The reduction of the rifabutin 

dose to 150 mg 3 times per week may be indicated for select PIs 

when co-administered with ritonavir as a pharmacokinetic enhancer. 

The Summary of Product Characteristics of the co-administered 

protease inhibitor should be consulted for specific 

recommendations. 

Consideration should be given to official guidance on the 

appropriate treatment of tuberculosis in HIV-infected patients. 

 

Rifampicin Although rifampicin may induce metabolism of ritonavir, limited 

data indicate that when high doses of ritonavir (600 mg twice daily) 

is co-administered with rifampicin, the additional inducing effect of 

rifampicin (next to that of ritonavir itself) is small and may have no 

clinical relevant effect on ritonavir levels in high-dose ritonavir 

therapy. 

The effect of ritonavir on rifampicin is not known. 

 

Voriconazole 200 q12 h 400 q12 h ↓ 82% ↓ 66% 

 200 q12 h 100 q12 h ↓ 39% ↓ 24% 

 Concomitant use of ritonavir dosed as an antiretroviral agent and 

voriconazole is contraindicated due to reduction in voriconazole 

concentrations (see section 4.3). Co-administration of voriconazole 

and ritonavir dosed as a pharmacokinetic enhancer should be 

avoided, unless an assessment of the benefit/risk to the patient 

justifies the use of voriconazole. 

 

Atovaquone Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent induces glucuronidation and as a result is 

expected to decrease the plasma concentrations of atovaquone. 

Careful monitoring of serum levels or therapeutic effects is 

recommended when atovaquone is concomitantly administered with 

ritonavir. 

 

Bedaquiline No interaction study is available with ritonavir only. In an 

interaction study of single-dose bedaquiline and multiple dose 

lopinavir/ritonavir, the AUC of bedaquiline was increased by 22%. 

This increase is likely due to ritonavir and a more pronounced effect 

may be observed during prolonged co-administration. Due to the 

risk of bedaquiline related adverse events, co-administration should 

be avoided. If the benefit outweighs the risk, co-administration of 

bedaquiline with ritonavir must be done with caution. More 

frequent electrocardiogram monitoring and monitoring of 

transaminases is recommended (see section 4.4 and refer to the 

bedaquiline Summary of Product Characteristics). 



20 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

 

Clarithromycin 500 q12 h 200 q8 h ↑ 77% ↑ 31% 

 

14-OH clarithromycin metabolite   ↓ 100% ↓ 99% 

 Due to the large therapeutic window of clarithromycin no dose 

reduction should be necessary in patients with normal renal 

function. 

Clarithromycin doses greater than 1 g per day should not be 

co-administered with ritonavir dosed as an antiretroviral agent or as 

a pharmacokinetic enhancer. For patients with renal impairment, a 

clarithromycin dose reduction should be considered: for patients 

with creatinine clearance of 30 to 60 ml/min the dose should be 

reduced by 50%, for patients with creatinine clearance less than 

30 ml/min the dose should be reduced by 75%. 

 

Delamanid No interaction study is available with ritonavir only. In a healthy 

volunteer drug interaction study of delamanid 100 mg twice daily 

and lopinavir/ritonavir 400/100 mg twice daily for 14 days, the 

exposure of the delamanid metabolite DM-6705 was 30% 

increased. Due to the risk of QTc prolongation associated with 

DM-6705, if co-administration of delamanid with ritonavir is 

considered necessary, very frequent ECG monitoring throughout the 

full delamanid treatment period is recommended (see section 4.4 

and refer to the delamanid Summary of Product Characteristics) 

 

Erythromycin, itraconazole Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A4 and as a result is expected to 

increase the plasma concentrations of erythromycin and 

itraconazole. Careful monitoring of therapeutic and adverse effects 

is recommended when erythromycin or itraconazole is used 

concomitantly administered with ritonavir. 

 

Ketoconazole 200 daily 500 q12 h ↑ 3.4-fold ↑ 55% 

 Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole. 

Due to an increased incidence of gastrointestinal and hepatic 

adverse reactions, a dose reduction of ketoconazole should be 

considered when co-administered with ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer. 

 

Sulfamethoxazole/Trimethoprim2 800/160, single 

dose 

500 q12 h ↓ 20%/↑ 20% ↔ 

 Dose alteration of sulfamethoxazole/trimethoprim during 

concomitant ritonavir therapy should not be necessary. 

 

Antipsychotics/Neuroleptics     

Clozapine, pimozide Ritonavir co-administration is likely to result in increased plasma 

concentrations of clozapine or pimozide and is therefore 

contraindicated (see section 4.3). 

 

Haloperidol, risperidone, 

thioridazine 

Ritonavir dosed as an antiretroviral agent is likely to inhibit 

CYP2D6 and as a result is expected to increase concentrations of 

haloperidol, risperidone and thioridazine. Careful monitoring of 

therapeutic and adverse effects is recommended when these 

medicines are concomitantly administered with antiretroviral doses 

of ritonavir. 

 



21 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 
Lurasidone Due to CYP3A inhibition by ritonavir, concentrations of lurasidone are 

expected to increase. The concomitant administration with lurasidone is 

contraindicated (see section 4.3). 

 

Quetiapine Due to CYP3A inhibition by ritonavir, concentrations of quetiapine 

are expected to increase. Concomitant administration of ritonavir 

and quetiapine is contraindicated as it may increase 

quetiapine-related toxicity (see section 4.3). 

 

β2-agonist (long acting)     

Salmeterol Ritonavir inhibits CYP3A4 and as a result a pronounced increase in 

the plasma concentrations of salmeterol is expected. Therefore 

concomitant use is not recommended. 

 

Calcium channel antagonists     

Amlodipine, diltiazem, nifedipine Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A4 and as a result is expected to 

increase the plasma concentrations of calcium channel antagonists. 

Careful monitoring of therapeutic and adverse effects is 

recommended when these medicines are concomitantly 

administered with ritonavir. 

 

Endothelin antagonists     

Bosentan Co-administration of bosentan and ritonavir may increase steady 

state bosentan maximum concentrations (Cmax) and area under the 

curve (AUC). 

 

Riociguat Serum concentrations may be increased due to CYP3A and P-gp 

inhibition by ritonavir. The co-administration of riociguat with 

ritonavir is not recommended (see section 4.4 and refer to riociguat 

SmPC). 

 

Ergot derivatives     

Dihydroergotamine, ergonovine, 

ergotamine, methylergonovine 

Ritonavir co-administration is likely to result in increased plasma 

concentrations of ergot derivatives and is therefore contraindicated 

(see section 4.3). 

 

GI motility agent     

Cisapride Ritonavir co-administration is likely to result in increased plasma 

concentrations of cisapride and is therefore contraindicated (see 

section 4.3). 

 

HCV Direct Acting Antiviral  

Glecaprevir/pibrentasvir Serum concentrations may be increased due to P-glycoprotein, 

BCRP and OATP1B inhibition by ritonavir. 

 

Concomitant administration of glecaprevir/pibrentasvir and 

ritonavir is not recommended due to an increased risk of ALT 

elevations associated with increased glecaprevir exposure. 

 

HCV protease inhibitor     

Simeprevir 200 qd 100 q12 h ↑ 7.2-fold ↑ 4.7-fold 

 Ritonavir increases plasma concentrations of simeprevir as a result 

of CYP3A4 inhibition. It is not recommended to co-administer 

ritonavir with simeprevir. 

 

HMG co-A reductase inhibitors     



22 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

Atorvastatin, fluvastatin, lovastatin, 

pravastatin, rosuvastatin, simvastatin 

HMG-CoA reductase inhibitors which are highly dependent on 

CYP3A metabolism, such as lovastatin and simvastatin, are 

expected to have markedly increased plasma concentrations when 

co-administered with ritonavir dosed as an antiretroviral agent or as 

a pharmacokinetic enhancer. Since increased concentrations of 

lovastatin and simvastatin may predispose patients to myopathies, 

including rhabdomyolysis, the combination of these medicinal 

products with ritonavir is contraindicated (see section 4.3). 

Atorvastatin is less dependent on CYP3A for metabolism. While 

rosuvastatin elimination is not dependent on CYP3A, an elevation 

of rosuvastatin exposure has been reported with ritonavir 

co-administration. The mechanism of this interaction is not clear, 

but may be the result of transporter inhibition. 

When used with ritonavir dosed as a pharmacokinetic enhancer or 

as an antiretroviral agent, the lowest possible doses of atorvastatin 

or rosuvastatin should be administered. The metabolism of 

pravastatin and fluvastatin is not dependent on CYP3A, and 

interactions are not expected with ritonavir. If treatment with an 

HMG-CoA reductase inhibitor is indicated, pravastatin or 

fluvastatin is recommended. 

 

Hormonal contraceptive     

Ethinylestradiol 50 μg, single 

dose 

500 q12 h ↓ 40% ↓ 32% 

 Due to reductions in ethinylestradiol concentrations, barrier or other 

non-hormonal methods of contraception should be considered with 

concomitant ritonavir use when dosed as an antiretroviral agent or 

as a pharmacokinetic enhancer. Ritonavir is likely to change the 

uterine bleeding profile and reduce the effectiveness of 

estradiol-containing contraceptives (see section 4.4). 

 

Immunosuppressants     

Cyclosporine, tacrolimus, 

everolimus 

Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A4 and as a result is expected to 

increase the plasma concentrations of cyclosporine, tacrolimus or 

everolimus. 

Careful monitoring of therapeutic and adverse effects is 

recommended when these medicines are concomitantly 

administered with ritonavir. 

 

Lipid-modifying agents  

Lomitapide CYP3A4 inhibitors increase the exposure of lomitapide, with strong 

inhibitors increasing exposure approximately 27-fold.  Due to 

CYP3A inhibition by ritonavir, concentrations of lomitapide are 

expected to increase.  Concomitant use of ritonavir with lomitapide 

is contraindicated (see prescribing information for lomitapide) (see 

section 4.3). 

Phosphodiesterase (PDE5) 

inhibitors 

    

Avanafil 50, single dose 600 q12 h ↑ 13-fold ↑ 2.4-fold 

 Concomitant use of avanafil with ritonavir is contraindicated (see 

section 4.3). 

 

Sildenafil 100, single dose 500 q12 h ↑ 11-fold ↑ 4-fold 

 Concomitant use of sildenafil for the treatment of erectile 

dysfunction with ritonavir dosed as an antiretroviral agent or as a 

pharmacokinetic enhancer should be with caution and in no instance 



23 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

should sildenafil doses exceed 25 mg in 48 hours (see also section 

4.4). Concomitant use of sildenafil with ritonavir is 

contraindicated in pulmonary arterial hypertension patients (see 

section 4.3). 

 

Tadalafil 20, single dose 200 q12 h ↑ 124% ↔ 

 The concomitant use of tadalafil for the treatment of erectile 

dysfunction with ritonavir dosed as an antiretroviral agent or as a 

pharmacokinetic enhancer should be with caution at reduced doses 

of no more than 10 mg tadalafil every 72 hours with increased 

monitoring for adverse reactions (see section 4.4). 

 

When tadalafil is used concurrently with ritonavir in patients with 

pulmonary arterial hypertension, refer to the tadalafil Summary of 

Product Characteristics. 

 

Vardenafil 5, single dose 600 q12 h ↑ 49-fold ↑ 13-fold 

 Concomitant use of vardenafil with ritonavir is contraindicated (see 

section 4.3). 

 

Sedatives/hypnotics     

Clorazepate, diazepam, estazolam, 

flurazepam, oral and parenteral 

midazolam 

Ritonavir co-administration is likely to result in increased plasma 

concentrations of clorazepate, diazepam, estazolam and flurazepam 

and is therefore contraindicated (see section 4.3). 

Midazolam is extensively metabolised by CYP3A4. 

Co-administration with ritonavir may cause a large increase in the 

concentration of this benzodiazepine. No medicinal product 

interaction study has been performed for the co-administration of 

ritonavir with benzodiazepines. 

Based on data for other CYP3A4 inhibitors, plasma concentrations 

of midazolam are expected to be significantly higher when 

midazolam is given orally. Therefore, ritonavir should not be 

co-administered with orally administered midazolam (see section 

4.3), whereas caution should be used with co-administration of 

ritonavir and parenteral midazolam. Data from concomitant use of 

parenteral midazolam with other protease inhibitors suggest a 

possible 3 – 4 fold increase in midazolam plasma levels. If ritonavir 

is co-administered with parenteral midazolam, it should be done in 

an intensive care unit (ICU) or similar setting which ensures close 

clinical monitoring and appropriate medical management in case of 

respiratory depression and/or prolonged sedation. Dosage 

adjustment for midazolam should be considered, especially if more 

than a single dose of midazolam is administered. 

 

Triazolam 0.125, single 

dose 

200, 4 doses ↑ > 20 fold ↑ 87% 

 Ritonavir co-administration is likely to result in increased plasma 

concentrations of triazolam and is therefore contraindicated (see 

section 4.3). 

 

Pethidine 50, oral single 

dose 

500 q12 h ↓ 62% ↓ 59% 

Norpethidine metabolite   ↑ 47% ↑ 87% 

 The use of pethidine and ritonavir is contraindicated due to the 

increased concentrations of the metabolite, norpethidine, which has 

both analgesic and CNS stimulant activity. Elevated norpethidine 

concentrations may increase the risk of CNS effects (e.g., seizures), 

see section 4.3. 



24 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

 

Alprazolam 1, single dose 200 q12 h, 

2 days 

↑ 2.5 fold ↔ 

  500 q12 h, 

10 days 

↓ 12% ↓ 16% 

 Alprazolam metabolism was inhibited following the introduction of 

ritonavir. After ritonavir use for 10 days, no inhibitory effect of 

ritonavir was observed. Caution is warranted during the first several 

days when alprazolam is co-administered with ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer, before 

induction of alprazolam metabolism develops. 

 

Buspirone Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A and as a result is expected to 

increase the plasma concentrations of buspirone. Careful monitoring 

of therapeutic and adverse effects is recommended when buspirone 

concomitantly administered with ritonavir. 

 

 

 

 

Sleeping agent     

Zolpidem 5 200, 4 doses ↑ 28% ↑ 22% 

 Zolpidem and ritonavir may be co-administered with careful 

monitoring for excessive sedative effects. 

 

Smoke cessation     

Buproprion 150 100 q12 h ↓ 22% ↓ 21% 

 150 600 q12 h ↓ 66% ↓ 62% 

 Bupropion is primarily metabolised by CYP2B6. Concurrent 

administration of bupropion with repeated doses of ritonavir is 

expected to decrease bupropion levels. These effects are thought to 

represent induction of bupropion metabolism. However, because 

ritonavir has also been shown to inhibit CYP2B6 in vitro, the 

recommended dose of bupropion should not be exceeded. In 

contrast to long-term administration of ritonavir, there was no 

significant interaction with bupropion after short-term 

administration of low doses of ritonavir (200 mg twice daily for 

2 days), suggesting reductions in bupropion concentrations may 

have onset several days after initiation of ritonavir 

co-administration. 

 

Steroids     

Inhaled, injectable or intranasal 

fluticasone propionate, budesonide, 

triamcinolone 

Systemic corticosteroid effects including Cushing's syndrome and 

adrenal suppression (plasma cortisol levels were noted to be 

decreased 86% in the above study) have been reported in patients 

receiving ritonavir and inhaled or intranasal fluticasone propionate; 

similar effects could also occur with other corticosteroids 

metabolised by CYP3A e.g., budesonide and triamcinolone. 

Consequently, concomitant administration of ritonavir dosed as an 

antiretroviral agent or as a pharmacokinetic enhancer and these 

glucocorticoids is not recommended unless the potential benefit of 

treatment outweighs the risk of systemic corticosteroid effects (see 

section 4.4). A dose reduction of the glucocorticoid should be 

considered with close monitoring of local and systemic effects or a 

switch to a glucocorticoid, which is not a substrate for CYP3A4 

(e.g., beclomethasone). Moreover, in case of withdrawal of 



25 

Co-administered Medicinal 

Products 

Dose of Co-

administered 

Medicinal 

Products (mg) 

Dose of 

ritonavir 

(mg) 

Effect on Co-

administered 

Medicinal 

Products AUC 

Effect on Co-

administered 

Medicinal 

Products 

Cmax 

glucocorticoids progressive dose reduction may be required over a 

longer period. 

 

Dexamethasone Ritonavir dosed as a pharmacokinetic enhancer or as an 

antiretroviral agent inhibits CYP3A and as a result is expected to 

increase the plasma concentrations of dexamethasone. Careful 

monitoring of therapeutic and adverse effects is recommended when 

dexamethasone is concomitantly administered with ritonavir. 

 

Prednisolone 20 200 q12 h ↑ 28% ↑ 9% 

 Careful monitoring of therapeutic and adverse effects is 

recommended when prednisolone is concomitantly administered 

with ritonavir. The AUC of the metabolite prednisolone increased 

by 37 and 28% after 4 and 14 days ritonavir, respectively. 

 

Thyroid hormone replacement 

therapy 

 

Levothyroxine  Post-marketing cases have been reported indicating a potential 

interaction between ritonavir containing products and 

levothyroxine. Thyroid-stimulating hormone (TSH) should be 

monitored in patients treated with levothyroxine at least the first 

month after starting and/or ending ritonavir treatment. 

 ND: Not determined 
1 Based on a parallel group comparison 
2 Sulfamethoxazole was co-administered with trimethoprim 

 

Cardiac and neurologic events have been reported when ritonavir has been co-administered with 

disopyramide, mexiletine or nefazodone. The possibility of medicinal product interaction cannot be 

excluded. 

 

In addition to the interactions listed above, as ritonavir is highly protein bound, the possibility of 

increased therapeutic and toxic effects due to protein binding displacement of concomitant medicinal 

products should be considered. 

 

Ritonavir dosed as a pharmacokinetic enhancer 

 

Important information regarding medicinal product interactions when ritonavir is used a 

pharmacokinetic enhancer is also contained in the Summary of Product Characteristics of the 

co-administered protease inhibitor. 

 

Proton pump inhibitors and H2-receptor antagonists 

Proton pump inhibitors and H2-receptor antagonists (e.g. omeprazole or ranitidine) may reduce 

concentrations for co-administered protease inhibitors. For specific information regarding the impact 

of co-administration of acid reducing agents, refer to the Summary of Product Characteristics of the 

co-administered protease inhibitor. Based on interaction studies with the ritonavir boosted protease 

inhibitors (lopinavir/ritonavir, atazanavir), concurrent administration of omeprazole or ranitidine does 

not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of 

exposure (about 6 - 18%). 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

A large amount (6100 live births) of pregnant women were exposed to ritonavir during pregnancy; of 

these, 2800 live births were exposed during the first trimester. These data largely refer to exposures 



26 

where ritonavir was used in combination therapy and not at therapeutic ritonavir doses but at lower 

doses as a pharmacokinetic enhancer for other PIs. These data indicate no increase in the rate of birth 

defects compared to rates observed in population-based birth defect surveillance systems. Animal data 

have shown reproductive toxicity (see section 5.3). Ritonavir can be used during pregnancy if 

clinically needed.   

 

Ritonavir adversely interacts with oral contraceptives (OCs). Therefore, an alternative, effective and 

safe method of contraception should be used during treatment. 

 

Breast-feeding 

 

Limited published data reports that ritonavir is present in human milk. 

 

There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on 

milk production.  Because of the potential for (1) HIV transmission (in HIV-negative infants), (2) 

developing viral resistance (in HIV-postive infants) and (3) serious adverse reactions in a breastfed 

infant,  HIV infected women should not breast feed their infants under any circumstances if they are 

receiving ritonavir. 

 

Fertility 

 

No human data on the effect of ritonavir on fertility are available. Animal studies do not indicate 

harmful effects of ritonavir on fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effects on the ability to drive and use machines have been performed. Dizziness is a 

known undesirable effect that should be taken into account when driving or using machinery. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

 

Ritonavir dosed as a pharmacokinetic enhancer 

Adverse reactions associated with the use of ritonavir as a pharmacokinetic enhancer are dependent on 

the specific co-administered PI. For information on adverse reactions refer to the SPC of the specific 

co-administered PI. 

 

Ritonavir dosed as an antiretroviral agent 

 

Adverse reactions from clinical trials and post-marketing experience in adult patients 

 

The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in 

combination with other antiretroviral drugs were gastrointestinal (including diarrhoea, nausea, 

vomiting, abdominal pain (upper and lower)), neurological disturbances (including paraesthesia and 

oral paraesthesia) and fatigue/asthenia. 

 

Tabulated list of adverse reactions 

 

The following adverse reactions of moderate to severe intensity with possible or probable relationship 

to ritonavir have been reported. Within each frequency grouping, undesirable effects are presented in 

order of decreasing seriousness: 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); not known (cannot be estimated from the 

available data). 

 

Events noted as having frequency not known were identified via post-marketing surveillance. 

 



27 

Adverse reactions in clinical studies and post-marketing in adult patients 

System Order Class Frequency Adverse reaction 

Blood and lymphatic system 

disorders 

Common 

 

 

 

 

Uncommon 

Decreased white blood cells, decreased 

haemoglobin, decreased neutrophils, 

increased eosinophils, thrombocytopenia 

 

Increased neutrophils 

 

Immune system disorders Common 

 

 

Rare 

Hypersensitivity including urticaria, and 

face oedema 

 

Anaphylaxis 

 

Metabolism and nutrition 

disorders 

Common 

 

 

 

 

 

Uncommon 

 

Rare 

Hypercholesterolaemia, 

hypertriglyceridaemia, gout, oedema and 

peripheral oedema, dehydration (usually 

associated with gastrointestinal 

symptoms) 

 

Diabetes mellitus 

 

Hyperglycaemia 

 

Nervous system disorders Very common 

 

 

 

Common 

Dysgeusia, oral and peripheral 

paraesthesia, headache, dizziness, 

peripheral neuropathy 

 

Insomnia, anxiety, confusion, disturbance 

in attention, syncope, seizure 

 

Eye disorders Common Blurred vision 

 

Cardiac disorders Uncommon Myocardial infarction 

 

Vascular disorders Common Hypertension, hypotension including 

orthostatic hypotension, peripheral 

coldness 

 

Respiratory, thoracic and 

mediastinal disorders 

Very common Pharyngitis, oropharyngeal pain, cough 

 

Gastrointestinal disorders Very common 

 

 

 

 

Common 

Abdominal pain (upper and lower), 

nausea, diarrhoea (including severe with 

electrolyte imbalance), vomiting, 

dyspepsia 

 

Anorexia, flatulence, mouth ulcer, 

gastrointestinal haemorrhage, 

gastroesophageal reflux disease, 

pancreatitis 

 

Hepatobiliary disorders Common Hepatitis (including increased AST, ALT, 

GGT), blood bilirubin increased 

(including jaundice) 

 

Skin and subcutaneous tissue 

disorders 

Very common 

 

 

Common 

 

Rare 

Pruritus, rash (including erythematous and 

maculopapular) 

 

Acne 

 

Stevens Johnson syndrome, toxic 

epidermal necrolysis (TEN) 

 



28 

Musculoskeletal and connective 

tissue disorders 

Very common 

 

Common 

Arthralgia and back pain 

 

Myositis, rhabdomyolysis, myalgia, 

myopathy/CPK increased 

 

Renal and urinary disorders Common 

 

 

 

Uncommon 

Increased urination, renal impairment (e.g. 

oliguria, elevated creatinine) 

 

Acute renal failure 

 

Reproductive system and breast 

disorders 

Common Menorrhagia 

General disorders and 

administration site conditions 

Very common 

 

 

Common 

Fatigue including asthenia, flushing, 

feeling hot 

 

Fever, weight loss 

 

Investigations Common 

 

 

Uncommon 

Increased amylase, decreased free and 

total thyroxin 

 

Increased glucose, increased magnesium, 

increased alkaline phosphatase 

 

Description of selected adverse reactions 

 

Hepatic transaminase elevations exceeding five times the upper limit or normal, clinical hepatitis, and 

jaundice have occurred in patients receiving ritonavir alone or in combination with other 

antiretrovirals. 

 

Metabolic parameters 

 

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

4.4). 

 

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 can occur many months 

after initiation of treatment (see section 4.4). 

 

Pancreatitis has been observed in patients receiving ritonavir therapy, including those who developed 

hypertriglyceridemia. In some cases fatalities have been observed. Patients with advanced HIV disease 

may be at risk of elevated triglycerides and pancreatitis (see section 4.4). 

 

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

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

The frequency of this is unknown (see section 4.4). 

 

Paediatric populations 

The safety profile of ritonavir in children 2 years of age and older is similar to that seen in adults. 

 

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 

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


29 

 

Symptoms 

 

Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took 

ritonavir 1,500 mg/day for two days and reported paraesthesia, which resolved after the dose was 

decreased. A case of renal failure with eosinophilia has been reported. 

 

The signs of toxicity observed in animals (mice and rats) included decreased activity, ataxia, dyspnoea 

and tremors. 

 

Management 

 

There is no specific antidote for overdose with ritonavir. Treatment of overdose with ritonavir should 

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

clinical status of the patient. Due to the solubility characteristics and possibility of transintestinal 

elimination, it is proposed that management of overdose could entail gastric lavage and administration 

of activated charcoal. Since ritonavir is extensively metabolised by the liver and is highly protein 

bound, dialysis is unlikely to be beneficial in significant removal of the medicine. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: antivirals for systemic use, protease inhibitors ATC code: J05AE03. 

 

Ritonavir dosed as a pharmacokinetic enhancer 

 

Pharmacokinetic enhancement by ritonavir is based on ritonavir’s activity as a potent inhibitor of 

CYP3A- mediated metabolism. The degree of enhancement is related to the metabolic pathway of the 

co-administered protease inhibitor and the impact of the co-administered protease inhibitor on the 

metabolism of ritonavir. Maximal inhibition of metabolism of the co-administered protease inhibitor is 

generally achieved with ritonavir doses of 100 mg daily to 200 mg twice daily, and is dependent on 

the co-administered protease inhibitor. For additional information on the effect of ritonavir on 

co-administered protease inhibitor metabolism, see section 4.5 and refer to the Summary of Product 

Characteristics of the particular co-administered PIs. 

 

Ritonavir dosed as an antiretroviral agent 

 

Ritonavir is an orally active peptidomimetic inhibitor of the HIV-1 and HIV-2 aspartyl proteases. 

Inhibition of HIV protease renders the enzyme incapable of processing the gag-pol polyprotein 

precursor which leads to the production of HIV particles with immature morphology that are unable to 

initiate new rounds of infection. Ritonavir has selective affinity for the HIV protease and has little 

inhibitory activity against human aspartyl proteases. 

 

Ritonavir was the first protease inhibitor (approved in 1996) for which efficacy was proven in a study 

with clinical endpoints. However, due to ritonavir’s metabolic inhibitory properties its use as a 

pharmacokinetic enhancer of other protease inhibitors is the prevalent use of ritonavir in clinical 

practice (see section 4.2). 

 

Effects on the electrocardiogram 

 

QTcF interval was evaluated in a randomised, placebo and active (moxifloxacin 400 mg once daily) 

controlled crossover study in 45 healthy adults, with 10 measurements over 12 hours on Day 3. The 

maximum mean (95% upper confidence bound) difference in QTcF from placebo was 5.5 (7.6) for 

400 mg twice daily ritonavir. The Day 3 ritonavir exposure was approximately 1.5 fold higher than 

that observed with the 600 mg twice daily dose at steady state. No subject experienced an increase in 



30 

QTcF of ≥ 60 msec from baseline or a QTcF interval exceeding the potentially clinically relevant 

threshold of 500 msec. 

 

Modest prolongation of the PR interval was also noted in subjects receiving ritonavir in the same study 

on Day 3. The mean changes from baseline in PR interval ranged from 11.0 to 24.0 msec in the 

12 hour interval post dose. Maximum PR interval was 252 msec and no second or third degree heart 

block was observed (see section 4.4). 

 

Resistance 

 

Ritonavir-resistant isolates of HIV-1 have been selected in vitro and isolated from patients treated with 

therapeutic doses of ritonavir. 

 

Reduction in the antiretroviral activity of ritonavir is primarily associated with the protease mutations 

V82A/F/T/S and I84V. Accumulation of other mutations in the protease gene (including at positions 

20, 33, 36, 46, 54, 71, and 90) can also contribute to ritonavir resistance. In general, as mutations 

associated with ritonavir resistance accumulate, susceptibility to select other PIs may decrease due to 

cross-resistance. The Summary of Product Characteristics of other protease inhibitors or official 

continuous updates should be consulted for specific information regarding protease mutations 

associated with reduced response to these agents. 

 

Clinical pharmacodynamic data 

 

The effects of ritonavir (alone or combined with other antiretroviral agents) on biological markers of 

disease activity such as CD4 cell count and viral RNA were evaluated in several studies involving 

HIV-1 infected patients. The following studies are the most important. 

 

Adult Use 

A controlled study completed in 1996 with ritonavir as add-on therapy in HIV-1 infected patients 

extensively pre-treated with nucleoside analogues and baseline CD4 cell counts ≤ 100 cells/μl showed 

a reduction in mortality and AIDS defining events. The mean average change from baseline over 

16 weeks for HIV RNA levels was -0.79 log10 (maximum mean decrease: 1.29 log10) in the ritonavir 

group versus -0.01 log10 in the control group. The most frequently used nucleosides in this study were 

zidovudine, stavudine, didanosine and zalcitabine. 

 

In a study completed in 1996 recruiting less advanced HIV-1 infected patients (CD4 200-500 cells/μl) 

without previous antiretroviral therapy, ritonavir in combination with zidovudine or alone reduced 

viral load in plasma and increased CD4 count. The mean average change from baseline over 48 weeks 

for HIV RNA levels was -0.88 log10 in the ritonavir group versus -0.66 log10 in the ritonavir + 

zidovudine group versus -0.42 log10 in the zidovudine group. 

 

The continuation of ritonavir therapy should be evaluated by viral load because of the possibility of 

the emergence of resistance as described under section 4.1. 

 

Paediatric Use 

In an open label trial completed in 1998 in HIV infected, clinically stable children there was a 

significant difference (p = 0.03) in the detectable RNA levels in favour of a triple regimen (ritonavir, 

zidovudine and lamivudine) following 48 weeks treatment. 

 

In a study completed in 2003, 50 HIV-1 infected, protease inhibitor and lamivudine naïve children age 

4 weeks to 2 years received ritonavir 350 or 450 mg/m2 every 12 hours co-administered with 

zidovudine 160 mg/m2 every 8 hours and lamivudine 4 mg/kg every 12 hours. In intent to treat 

analyses, 72% and 36% of patients achieved reduction in plasma HIV-1 RNA of ≤ 400 copies/ml at 

Week 16 and 104, respectively. Response was similar in both dosing regimens and across patient age. 

 

In a study completed in 2000, 76 HIV-1 infected children aged 6 months to 12 years who were 

protease inhibitor naive and naive to lamivudine and/or stavudine received ritonavir 350 or 450 mg/m2 



31 

every 12 hours co-administered with lamivudine and stavudine. In intent to treat analyses, 50% and 

57% of patients in the 350 and 450 mg/m2 dose groups, respectively, achieved reduction in plasma 

HIV-1 RNA to ≤ 400 copies/ml at Week 48. 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

There is no parenteral formulation of ritonavir, therefore the extent of absorption and absolute 

bioavailability have not been determined. The pharmacokinetics of ritonavir during multiple dose 

regimens were studied in non-fasting HIV-infected adult volunteers. Upon multiple dosing, ritonavir 

accumulation is slightly less than predicted from a single dose due to a time and dose-related increase 

in apparent clearance (Cl/F). Trough concentrations of ritonavir decrease over time, possibly due to 

enzyme induction, but appeared to stabilise by the end of 2 weeks. The time to maximum 

concentration (Tmax) remained constant at approximately 4 hours with increasing dose. Renal clearance 

averaged less than 0.1 l/h and was relatively constant throughout the dosage range. 

 

The pharmacokinetic parameters observed with various dosing schemes of ritonavir alone are shown 

in the table below. Plasma concentrations of ritonavir after administration of a single 100 mg dose 

tablet are similar to the 100 mg soft gelatin capsule under fed conditions. 

 

Ritonavir dosing regimen 

 
 100 mg once 

daily 

100 mg twice 

daily1 

200 mg once 

daily 

200 mg twice 

daily 

600 mg twice 

daily 

Cmax (μg/ml) 0.84 ± 0.39 0.89 3.4 ± 1.3 4.5 ± 1.3 11.2 ± 3.6 

Ctrough (μg/ml) 0.08 ± 0.04 0.22 0.16 ± 0.10 0.6 ± 0.2 3.7 ± 2.6 

AUC12 or 24 

(μg•h/ml) 

6.6 ± 2.4 6.2 20.0 ± 5.6 21.92 ± 6.48 77.5 ± 31.5 

t1/2 (h) ~5 ~5 ~4 ~8 ~3 to 5 

Cl/F (L/h) 17.2 ± 6.6 16.1 10.8 ± 3.1 10.0 ± 3.2 8.8 ± 3.2 
1 Values expressed as geometric means. Note: ritonavir was dosed after a meal for all listed regimens. 

 

Effects of food on oral absorption 

 

Food slightly decreases the bioavailability of the ritonavir tablet. Administration of a single 100 mg 

dose of ritonavir tablet with a moderate fat meal (857 kcal, 31% calories from fat) or a high fat meal 

(907 kcal, 52% calories from fat) was associated with a mean decrease of 20-23% in ritonavir AUC 

and Cmax. 

 

Distribution 

 

The apparent volume of distribution (VB/F) of ritonavir is approximately 20 – 40 l after a single 

600 mg dose. The protein binding of ritonavir in human plasma is approximately 98 - 99% and is 

constant over the concentration range of 1.0 – 100 μg/ml. Ritonavir binds to both human alpha 1-acid 

glycoprotein (AAG) and human serum albumin (HSA) with comparable affinities. 

 

Tissue distribution studies with 14C-labelled ritonavir in rats showed the liver, adrenals, pancreas, 

kidneys and thyroid to have the highest concentrations of ritonavir. Tissue to plasma ratios of 

approximately 1 measured in rat lymph nodes suggests that ritonavir distributes into lymphatic tissues. 

Ritonavir penetrates minimally into the brain. 

 

Metabolism 

 

Ritonavir was noted to be extensively metabolised by the hepatic cytochrome P450 system, primarily 

by the CYP3A isozyme family and to a lesser extent by the CYP2D6 isoform. Animal studies as well 

as in vitro experiments with human hepatic microsomes indicated that ritonavir primarily underwent 

oxidative metabolism. Four ritonavir metabolites have been identified in man. The isopropylthiazole 



32 

oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of parent 

compound. However, the AUC of the M-2 metabolite was approximately 3% of the AUC of parent 

compound. 

 

Low doses of ritonavir have shown profound effects on the pharmacokinetics of other protease 

inhibitors (and other products metabolised by CYP3A4) and other protease inhibitors may influence 

the pharmacokinetics of ritonavir (see section 4.5). 

 

Elimination 

 

Human studies with radiolabelled ritonavir demonstrated that the elimination of ritonavir was 

primarily via the hepatobiliary system; approximately 86% of radiolabel was recovered from stool, 

part of which is expected to be unabsorbed ritonavir. In these studies renal elimination was not found 

to be a major route of elimination of ritonavir. This was consistent with the observations in animal 

studies. 

 

Special populations 

 

No clinically significant differences in AUC or Cmax were noted between males and females. Ritonavir 

pharmacokinetic parameters were not statistically significantly associated with body weight or lean 

body mass. Ritonavir plasma exposures in patients 50 – 70 years of age when dosed 100 mg in 

combination with lopinavir or at higher doses in the absence of other protease inhibitors is similar to 

that observed in younger adults. 

 

Patients with impaired liver function 

After multiple dosing of ritonavir to healthy volunteers (500 mg twice daily) and subjects with mild to 

moderate hepatic impairment (Child Pugh Class A and B, 400 mg twice daily) exposure to ritonavir 

after dose normalisation was not significantly different between the two groups. 

 

Patients with impaired renal function 

Ritonavir pharmacokinetic parameters have not been studied in patients with renal impairment. 

However, since the renal clearance of ritonavir is negligible, no changes in the total body clearance are 

expected in patients with renal impairment. 

 

Paediatric patients 

Ritonavir steady-state pharmacokinetic parameters were evaluated in HIV infected children above 

2 years of age receiving doses ranging from 250 mg/m2 twice daily to 400 mg/m2 twice daily. 

Ritonavir concentrations obtained after 350 to 400 mg/m2 twice daily in paediatric patients were 

comparable to those obtained in adults receiving 600 mg (approximately 330 mg/m2) twice daily. 

Across dose groups, ritonavir oral clearance (CL/F/m2) was approximately 1.5 to 1.7 times faster in 

paediatric patients above 2 years of age than in adult subjects. 

 

Ritonavir steady-state pharmacokinetic parameters were evaluated in HIV infected children less than 

2 years of age receiving doses ranging from 350 to 450 mg/m2 twice daily. Ritonavir concentrations in 

this study were highly variable and somewhat lower than those obtained in adults receiving 600 mg 

(approximately 330 mg/m2) twice daily. Across dose groups, ritonavir oral clearance (CL/F/m2) 

declined with age with median values of 9.0 L/h/m2 in children less than 3 months of age, 7.8 L/h/m2 

in children between 3 and 6 months of age and 4.4 L/h/m2 in children between 6 and 24 months of age. 

 

5.3 Preclinical safety data 

 

Repeated dose toxicity studies in animals identified major target organs as the liver, retina, thyroid 

gland and kidney. Hepatic changes involved hepatocellular, biliary and phagocytic elements and were 

accompanied by increases in hepatic enzymes. Hyperplasia of the retinal pigment epithelium (RPE) 

and retinal degeneration have been seen in all of the rodent studies conducted with ritonavir, but have 

not been seen in dogs. Ultrastructural evidence suggests that these retinal changes may be secondary to 



33 

phospholipidosis. However, clinical trials revealed no evidence of medicinal product-induced ocular 

changes in humans. All thyroid changes were reversible upon discontinuation of ritonavir. 

Clinical investigation in humans has revealed no clinically significant alteration in thyroid function 

tests. Renal changes including tubular degeneration, chronic inflammation and proteinurea were noted 

in rats and are felt to be attributable to species-specific spontaneous disease. Furthermore, no clinically 

significant renal abnormalities were noted in clinical trials. 

 

Developmental toxicity observed in rats (embryolethality, decreased foetal body weight and 

ossification delays and visceral changes, including delayed testicular descent) occurred mainly at a 

maternally toxic dosage. Developmental toxicity in rabbits (embryolethality, decreased litter size and 

decreased foetal weights) occurred at a maternally toxic dosage. 

 

Ritonavir was not found to be mutagenic or clastogenic in a battery of in vitro and in vivo assays 

including the Ames bacterial reverse mutation assay using S. typhimurium and E. coli, the mouse 

lymphoma assay, the mouse micronucleus test and chromosomal aberration assays in human 

lymphocytes. 

 

Long term carcinogenicity studies of ritonavir in mice and rats revealed tumourigenic potential 

specific for these species, but are regarded as of no relevance for humans. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 

 

Tablet 

 

Copovidone 

Sorbitan laurate 

Silica, colloidal anhydrous 

Sodium chloride 

Sodium stearyl fumarate 

 

Film-coating 

 

Hypromellose 

Titanium dioxide (E171) 

Macrogols 

Hydroxypropylcellulose 

Talc 

Iron oxide yellow (E172) 

Silica, colloidal anhydrous 

Polysorbate 80 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf-life 

 

2 years. 

After first opening, use within 100 days. 

 

6.4 Special precautions for storage 

 

Do not store above 30C. 

Store in the original bottle in order to protect from moisture. 



34 

 

6.5 Nature and contents of container 

 

HDPE bottle with polypropylene screw cap with inbuilt desiccant.  

Pack sizes: 30, 90, 100 and multipack containing 90 (3 bottles of 30) film-coated tablets. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Mylan S.A.S. 

117 Allée des Parcs, 

Saint-Priest, 

69800, France 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/17/1242/001 

EU/1/17/1242/002 

EU/1/17/1242/003 

EU/1/17/1242/004 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 10 November 2017 

 

 

10. DATE OF REVISION OF THE TEXT 
 

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

http://www.ema.europa.eu 

  

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


35 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 

 



36 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

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

 

Generics UK Limited 

Station Close 

Potters Bar 

Hertfordshire 

EN6 1TL 

UNITED KINGDOM 

 

McDermott Laboratories Limited T/A Gerard Laboratories 

35/36 Baldoyle Industrial Estate 

Grange Road 

Dublin 13 

IRELAND 

 

Mylan Hungary Kft./Mylan Hungary Ltd. 

Mylan utca 1 

2900 Komarom 

HUNGARY 

 

Mylan Germany GmbH 

Zweigniederlassung Bad Homburg v. d. Hoehe,  

Benzstrasse 1,  

Bad Homburg v. d. Hoehe, 

Hessen, 61352,  

GERMANY 

 

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

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

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

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

• Periodic safety update reports (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. 



37 

 

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.  

 

  



38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



39 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



40 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ritonavir Mylan 100 mg film-coated tablets 

ritonavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg of ritonavir. 

 

 

3. LIST OF EXCIPIENTS 

 

High in sodium – see leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablets 

 

30 film-coated tablets 

90 film-coated tablets 

100 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

To be taken with food. 

The tablets should be swallowed whole and not chewed, broken or crushed. 

 

 

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 

 

After first opening, use within 100 days. 

 

Open date: __________ 



41 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original bottle in order to protect from moisture. 

 

 

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 Allée des Parcs, 

69800 Saint-Priest, 

France  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1242/001 30 film-coated tablets 

EU/1/17/1242/002 90 film-coated tablets 

EU/1/17/1242/003 100 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Ritonavir Mylan 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 



42 

SN 

NN 

  



43 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ritonavir Mylan 100 mg film-coated tablets 

ritonavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg of ritonavir. 

 

 

3. LIST OF EXCIPIENTS 

 

High in sodium – see leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablets 

 

30 film-coated tablets 

90 film-coated tablets 

100 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

To be taken with food. 

The tablets should be swallowed whole and not chewed, broken or crushed. 

 

 

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 

 

After first opening, use within 100 days. 



44 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original bottle in order to protect from moisture. 

 

 

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 Allée des Parcs, 

69800 Saint-Priest, 

France  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1242/001 30 film-coated tablets 

EU/1/17/1242/002 90 film-coated tablets 

EU/1/17/1242/003 100 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Ritonavir Mylan 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 



45 

SN 

NN 

 

  



46 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

OUTER CARTON OF MULTIPACK (WITH BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ritonavir Mylan 100 mg film-coated tablets 

ritonavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg of ritonavir. 

 

 

3. LIST OF EXCIPIENTS 

 

High in sodium – see leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablets 

 

Multipack: 90 (3 bottles of 30) film-coated tablets  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

To be taken with food. 

The tablets should be swallowed whole and not chewed, broken or crushed. 

 

 

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 

 

After first opening, use within 100 days. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 



47 

Do not store above 30C. 

Store in the original bottle in order to protect from moisture. 

 

 

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 Allée des Parcs, 

69800 Saint-Priest, 

France  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1242/004 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Ritonavir Mylan 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

  



48 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

BOTTLE LABEL OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ritonavir Mylan 100 mg film-coated tablets 

ritonavir 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 100 mg of ritonavir. 

 

 

3. LIST OF EXCIPIENTS 

 

High in sodium – see leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Film-coated tablets 

 

30 film-coated tablets. Component of a multipack can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use. 

To be taken with food. 

The tablets should be swallowed whole and not chewed, broken or crushed. 

 

 

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 

 

After first opening, use within 100 days. 

 

Open date: __________ 

 

 



49 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30C. 

Store in the original bottle in order to protect from moisture. 

 

 

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 Allée des Parcs, 

69800 Saint-Priest, 

France  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1242/004 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS ON USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

 

  



50 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
  



51 

Package leaflet: Information for the user 

 

Ritonavir Mylan 100 mg film-coated tablets 

ritonavir 

 

 

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

important information for you or your child. 

 

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

if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet 

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

2. What you need to know before you or your child takes Ritonavir Mylan 

3. How to take Ritonavir Mylan 

4. Possible side effects 

5. How to store Ritonavir Mylan 

6. Contents of the pack and other information 

 

 

1. What Ritonavir Mylan is and what it is used for 
Ritonavir Mylan contains the active substance ritonavir. Ritonavir is a protease inhibitor used to 

control HIV infection. Ritonavir is used in combination with other anti-HIV medicines 

(antiretrovirals) to control your HIV infection. Your doctor will discuss with you the best combination 

of medicines for you. 

 

Ritonavir Mylan is used by children 2 years of age or older, adolescents and adults who are infected 

with HIV, the virus which causes AIDS. 

 

 

2. What you need to know before you or your child takes Ritonavir Mylan 
 

Do not take Ritonavir Mylan 

- if you are allergic to ritonavir or any of the other ingredients of this medicine (see section 6). 
- if you have severe liver disease. 
- if you are currently taking any of the following medicines: 

- astemizole or terfenadine (commonly used to treat allergy symptoms – these medicines 
may be available without prescription); 

- amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine (used to 
correct irregular heartbeats); 

- dihydroergotamine, ergotamine (used to treat migraine headache); 
- ergonovine, methylergonovine (used to stop excessive bleeding that may occur following 

childbirth or an abortion); 

- clorazepate, diazepam, estazolam, flurazepam, triazolam or oral (taken by mouth) 
midazolam (used to help you sleep and/or relieve anxiety); 

- clozapine, pimozide, (used to treat abnormal thoughts or feelings); 
- quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder); 

− lurasidone (used to treat depression); 

− ranolazine (used to treat chronic chest pain [angina]); 
- pethidine, piroxicam, propoxyphene (used to relieve pain); 
- cisapride (used to relieve certain stomach problems); 



52 

- rifabutin (used to prevent/treat certain infections)*; 
- voriconazole (used to treat fungal infections)*; 
- simvastatin, lovastatin (used to lower blood cholesterol);  
- neratinib (used to treat breast cancer); 
- lomitapide (used to lower blood cholesterol); 
- alfuzosin (used to treat enlarged prostate gland); 
- fusidic acid (used to treat bacterial infections); 
- sildenafil if you suffer from a lung disease called pulmonary arterial hypertension that 

makes breathing difficult. Patients without this disease may use sildenafil for impotence 

(erectile dysfunction) under their doctor’s supervision (see the section on Other 

medicines and Ritonavir Mylan); 

- avanafil or vardenafil (used to treat erectile dysfunction); 
- colchicine (used to treat gout) if you have kidney and/or liver problems (see the section 

on Other medicines and Ritonavir Mylan); 

- products containing St John’s wort (Hypericum perforatum) as this may stop ritonavir 
from working properly. St John’s wort is often used in herbal medicines that you can buy 

yourself. 

* Your doctor may decide that you can take rifabutin and/or voriconazole with a booster (lower 

dose) of ritonavir but a full dose of ritonavir must not be taken together with these two 

medicines. 

 

If you are currently taking any of these medicines, ask your doctor about switching to a different 

medicine while you are taking Ritonavir Mylan. 

 

Also read the list of medicines under ‘Other medicines and Ritonavir Mylan’ for use with certain other 

medicines which require special care. 

 

Warnings and precautions 

 

Talk to your doctor before taking Ritonavir Mylan. 

 

Important information 

- If Ritonavir Mylan is taken in combination with other antiretroviral medicines, it is important 
that you also carefully read the leaflets that are provided with these other medicines. There may 

be additional information in those leaflets about situations when ritonavir should be avoided. If 

you have any further questions about Ritonavir Mylan (ritonavir) or the other medicines 

prescribed, please ask your doctor or pharmacist. 

- Ritonavir is not a cure for HIV infection or AIDS. 
- People taking ritonavir may still develop infections or other illnesses associated with HIV 

infection or AIDS. It is therefore important that you remain under the supervision of your doctor 

while taking Ritonavir Mylan. 

- 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. 

 

Tell your doctor if you have/had: 

 

- A history of liver disease. 
- Hepatitis B or C and are being treated with a combination of antiretroviral agents, as you are at 

a greater risk of a severe and potentially life threatening reaction because of the effect on the 

liver. Regular blood tests may be required to check your liver is working properly. 

- Haemophilia, as there have been reports of increased bleeding in patients with haemophilia 
who are taking this type of medicine (protease inhibitors). The reason for this is not known. 

You may need additional medicine to help your blood clot (factor VIII), in order to control any 

bleeding. 

- Erectile dysfunction, as the medicines used to treat erectile dysfunction can cause hypotension 
and prolonged erection. 



53 

- Diabetes, as there have been reports of worsening of or the development of diabetes (diabetes 
mellitus) in some patients taking protease inhibitors. 

- Kidney (renal) disease, since your doctor may need to check the dose of your other medicines 
(such as protease inhibitors). 

 

Tell your doctor if you experience: 

 

- Diarrhoea or vomiting that is not improving (persistent), as this may reduce how well the 
medicines you are taking work. 

- Feeling sick (nausea), vomiting or have stomach pain, because these may be signs of 
inflammation of the pancreas (pancreatitis). Some patients taking ritonavir can develop serious 

problems with their pancreas. Tell your doctor as soon as possible if this applies to you. 

- Symptoms of infection - inform your doctor immediately. Some patients with advanced HIV 
infection (AIDS) who then start anti-HIV treatment may develop the symptoms of infections 

they have had in the past even if they didn’t know they had had them. It is believed that this 

happens because the body's immune response improves and helps the body to fight these 

infections. 

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. 

- Joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty 
moving, tell your doctor, as this may be a sign of a problem that can destroy bone 

(osteonecrosis). Some patients taking a number of antiretroviral medicines may develop this 

disease. 

- Muscle pain, tenderness or weakness, particularly in combination with antiretroviral therapy 
including protease inhibitors and nucleoside analogues. On rare occasions these muscle 

disorders have been serious. (See section 4 Possible side effects) 

- Dizziness, lightheadedness, fainting spells or abnormal heartbeat. Some patients taking 
ritonavir may experience changes in the electrocardiogram (ECG). Tell your doctor if you have 

a heart defect or conduction defect. 

- If you have any other health concerns, discuss these with your doctor as soon as you can. 
 

Children and adolescents 

 

Ritonavir Mylan is not recommended in children below 2 years of age. 

 

Other medicines and Ritonavir Mylan 

 

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other 

medicines, including medicines obtained without a prescription. There are some medicines you cannot 

take at all with ritonavir. These are listed earlier in section 2, under ‘Do not take Ritonavir Mylan’. 

There are some other medicines that can only be used under certain circumstances as described below. 

 

The following warnings apply when Ritonavir Mylan is taken as a full dose. However, these warnings 

may also apply when Ritonavir Mylan is used in lower doses (a booster) with other medicines. 

 

Tell your doctor if you are taking any of the medicines listed below, as special care should be 

taken. 

 

- Sildenafil or tadalafil for impotence (erectile dysfunction). 
The dose and/or frequency of use of these medicines may need to be reduced to avoid 

hypotension and prolonged erection. You must not take Ritonavir Mylan with sildenafil if you 

suffer from pulmonary arterial hypertension (see also section 2. What you need to know 



54 

before you or your child takes Ritonavir Mylan). Tell your doctor if you are taking tadalafil 

for pulmonary arterial hypertension. 

- Colchicine (for gout) as ritonavir may raise the blood levels of this medicine. You must not take 
ritonavir with colchicine if you have kidney and/or liver problems (see also ‘Do not take 

Ritonavir Mylan’ above). 

- Digoxin (heart medicine). Your doctor may need to adjust the dose of digoxin and monitor you 
while you are taking digoxin and Ritonavir Mylan in order to avoid heart problems. 

- Hormonal contraceptives containing ethinylestradiol as ritonavir may reduce the effectiveness 
of these medicines. It is recommended that a condom or other non-hormonal method of 

contraception is used instead. You may also notice irregular uterine bleeding if you are taking 

this type of hormonal contraceptive with ritonavir. 

- Atorvastatin or rosuvastatin (for high cholesterol) as ritonavir may raise the blood levels of 
these medicines. Talk to your doctor before you take any cholesterol-reducing medicines with 

ritonavir (see also ‘Do not take Ritonavir Mylan’ above). 

- Steroids (e.g. dexamethasone, fluticasone propionate, prednisolone, triamcinolone) as ritonavir 
may raise the blood levels of these medicines which may lead to Cushing’s syndrome 

(development of a rounded face) and reduce production of the hormone cortisol. Your doctor 

may wish to reduce the steroid dose or monitor your side effects more closely. 

- Trazodone (a medicine for depression) as, unwanted effects like nausea, dizziness, low blood 
pressure and fainting can occur when taken with ritonavir. 

- Rifampicin and saquinavir (used for tuberculosis and HIV, respectively) as serious liver 
damage can occur when taken with ritonavir. 

- Bosentan, riociguat (used for pulmonary arterial hypertension) as ritonavir may increase the 
blood levels of this medicine. 

 

There are medicines that may not mix with ritonavir because their effects could increase or decrease 

when taken together. In some cases your doctor may need to perform certain tests, change the dose or 

monitor you regularly. This is why you should tell your doctor if you are taking any medicines, 

including those you have bought yourself or herbal products, but it is especially important to mention 

these: 

 

- amphetamine or amphetamine derivatives; 
- antibiotics (e.g. erythromycin, clarithromycin); 
- anticancer treatments (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, dasatinib, 

ibrutinib, nilotinib, venetoclax, vincristine, vinblastine); 

- anticoagulants (e.g. rivaroxaban, vorapaxar, warfarin); 
- antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nefazodone, 

nortriptyline, paroxetine, sertraline, trazodone); 

- antifungals (e.g. ketoconazole, itraconazole); 
- antihistamines (e.g. loratadine, fexofenadine); 
- antiretroviral medicines including HIV-protease inhibitors (amprenavir, atazanavir, darunavir, 

fosamprenavir, indinavir, nelfinavir, saquinavir, tipranavir) non-nucleoside reverse transcriptase 

inhibitors (NNRTI) (delavirdine, efavirenz, nevirapine), and others (didanosine, maraviroc, 

raltegravir, zidovudine); 

- anti-tuberculosis medicine (bedaquiline and delamanid); 
- antiviral medicine used to treat chronic hepatitis C virus (HCV) infection in adults (e.g. 

glecaprevir/pibrentasvir and simeprevir); 

- anxiety medicine, buspirone; 
- asthma medicine, theophylline, salmeterol; 
- atovaquone, a medicine used to treat a certain type of pneumonia and malaria; 
- buprenorphine, a medicine used for the treatment of chronic pain; 
- bupropion, a medicine used to help you stop smoking; 
- epilepsy medicines (e.g. carbamazepine, divalproex, lamotrigine, phenytoin); 
- heart medicines (e.g. disopyramide, mexiletine and calcium channel antagonists such as 

amlodipine, diltiazem and nifedipine); 

- immune system (e.g. cyclosporine, tacrolimus, everolimus); 
- levothyroxine (used to treat thyroid problems) 



55 

- morphine and morphine-like medicines used to treat severe pain (e.g. methadone, fentanyl); 
- sleeping pills (e.g. alprazolam, zolpidem) and also midazolam administered by injection; 
- tranquillisers (e.g. haloperidol, risperidone, thioridazine); 
- colchicine, a treatment for gout. 
 

There are some medicines you cannot take at all with ritonavir. These are listed earlier in section 2, 

under ‘Do not take Ritonavir Mylan’. 

 

Taking Ritonavir Mylan with food and drink 

 

Ritonavir Mylan tablets should be taken with food. 

 

Pregnancy and breast-feeding 

 

If you think you are pregnant or you are planning to become pregnant, it is very important that 

you discuss this with your doctor. 

 

There is a large amount of information on the use of ritonavir (the active ingredient in Ritonavir 

Mylan) during pregnancy. In general, pregnant mothers received ritonavir after the first three months 

of pregnancy at a lower dose (booster) along with other protease inhibitors. Ritonavir did not appear to 

increase the chance of developing birth defects compared to the general population. 

 

Ritonavir can pass into breast milk. To avoid transmitting the infection, mothers with HIV must not 

breast-feed their babies. 

 

Driving and using machines 

 

Ritonavir Mylan can cause dizziness. If you are affected do not drive or use machinery. 

 

Ritonavir Mylan contains sodium 

 

This medicine contains 87.75 mg of sodium in each tablet. This is equivalent to 4.4% of the 

recommended maximum daily dietary intake of sodium for an adult. Talk to your doctor or pharmacist 

if you need five or more tablets daily for a prolonged period, especially if you have been advised to 

follow a low salt (sodium) diet. 

 

 

3. How to take Ritonavir Mylan 
 

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

or pharmacist if you are not sure. Take this medicine one or two times a day every day with food. 

 

It is important that Ritonavir Mylan tablets are swallowed whole and not chewed, broken or crushed. 

 

Recommended doses of Ritonavir Mylan are: 

• if Ritonavir Mylan is used to boost the effects of certain other anti-HIV medicines the typical 
dose for adults is 1 to 2 tablets once or twice daily. For more detailed dose recommendations, 

including those for children, see the Package Leaflet of the anti-HIV medicines Ritonavir Mylan 

is given in combination with. 

• if your doctor prescribes a full dose, adults may be started on a dose of 3 tablets in the morning 
and 3 tablets 12 hours later, gradually increasing over a period of up to 14 days to the full dose 

of 6 tablets twice daily (totalling 1,200 mg per day). Children (2 - 12 years of age) will start 

with a dose smaller than this and continue up to the maximum allowed for their size. 

 

Your doctor will advise you on the dosage to be taken. 

 



56 

Other forms of this medicine may be more appropriate for children who have difficulty swallowing 

tablets. 

 

Ritonavir Mylan should be taken every day to help control your HIV, no matter how much better you 

feel. If a side effect is preventing you from taking Ritonavir Mylan as directed, tell your doctor 

straight away. During episodes of diarrhoea your doctor may decide that extra monitoring is needed. 

 

Always keep enough Ritonavir Mylan on hand so you don't run out. When you travel or need to stay 

in the hospital, make sure you have enough Ritonavir Mylan to last until you can get a new supply. 

 

If you take more Ritonavir Mylan than you should 

 

Numbness, tingling, or a “pins and needles” sensation may occur if you take too much ritonavir. If you 

realise you have taken more Ritonavir Mylan than you were supposed to, contact your doctor or the 

Accident and Emergency Department of your nearest hospital straight away. 

 

If you forget to take Ritonavir Mylan 

 

If you miss a dose, take the missed dose as soon as possible. If it is nearly time for the next dose, just 

take that one. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Ritonavir Mylan 

 

Even if you feel better, do not stop taking Ritonavir Mylan without talking to your doctor. Taking 

Ritonavir Mylan as recommended should give you the best chance of delaying resistance to the 

medicines. 

 

 

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. Also, the 

side effects of ritonavir when used with other antiretroviral medicines are dependent on the other 

medicines. 

So it is important that you carefully read the side effects section of the leaflets that are provided with 

these other medicines. 

 

Very common: may affect more than 1 in 10 people 

 

• upper or lower stomach ache 

• vomiting 

• diarrhoea (may be severe) 

• feeling sick (nausea) 

• flushing, feeling hot 

• headache 

• dizziness 

• pain in the throat 

• cough 

• upset stomach or indigestion 

• a tingling sensation or numbness in the 
hands, feet or around the lips and mouth 

• feeling weak/tired 

• bad taste in the mouth 

• damage to the nerves that can cause 
weakness and pain 

• itching 

• rash 

• joint pain and back pain 

 

Common: may affect up to 1 in 10 people 

 



57 

• allergic reactions including skin rashes 
(may be red, raised, itchy), severe 

swelling of the skin and other tissues 

• inability to sleep (insomnia) 

• anxiety 

• increase in cholesterol 

• increase in triglycerides 

• gout 

• stomach bleeding 

• inflammation of the liver and yellowing 
of skin or whites of the eyes 

• increase in urination 

• reduced kidney function 

• seizures (fits) 

• low levels of blood platelets 

• thirst (dehydration) 

• abnormally heavy periods 
 

 

 

• wind (flatulence) 

• loss of appetite 

• mouth ulcer 

• muscle aches (pain), tenderness or 
weakness 

• fever 

• weight loss 

• laboratory test results: changes in blood 
test results (such as blood chemistry and 

blood count) 

• confusion 

• difficulty paying attention 

• fainting 

• blurred vision 

• swelling of the hands and feet 

• high blood pressure 

• low blood pressure and feeling faint 
when getting up 

• coldness in the hands and feet 

• acne 
Uncommon: may affect up to 1 in 100 people  

 

• heart attack 

• diabetes 
 

 

• kidney failure 
 

 

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

 

 

• severe or life threatening skin reaction 
including blisters (Stevens Johnson 

syndrome, toxic epidermal necrolysis) 

 

• serious allergic reaction (anaphylaxis) 

• high levels of sugar in the blood 
 

 

Tell your doctor if you feel sick (nauseous), are vomiting, or have stomach pain, because these may 

be signs of an inflamed pancreas. Also tell your doctor if you experience joint stiffness, aches and 

pains (especially of the hip, knee and shoulder) and difficulty moving, as this may be a sign of 

osteonecrosis. See also section 2 What you need to know before you or your child takes Ritonavir 

Mylan.  

 

In patients with haemophilia type A and B, there have been reports of increased bleeding while taking 

this treatment or another protease inhibitor. Should this happen to you, seek immediate advice from 

your doctor. 

 

Abnormal liver function tests, hepatitis (inflammation of the liver), and rarely jaundice, have been 

reported in patients taking ritonavir. Some people had other illnesses or were taking other medicines. 

People with liver disease or hepatitis may have worsening of liver disease. 

 

There have been reports of muscle pain, tenderness or weakness, particularly when taking medicines 

to lower cholesterol in combination with antiretroviral therapy, including protease inhibitors and 

nucleoside analogues. On rare occasions these muscle disorders have been serious (rhabdomyolysis). 

In the event of unexplained or continual muscle pain, tenderness, weakness or cramps, stop taking the 

medicine, contact your doctor as soon as possible or go to the Accident and Emergency Department of 

your nearest hospital. 

 



58 

Inform your doctor as soon as possible if you experience any symptoms that suggest an allergic 

reaction after taking Ritonavir Mylan such as rash, hives or breathing difficulties. 

 

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

contact your doctor, pharmacist, Accident and Emergency department or if it is urgent get 

immediate medical help. 

 

Reporting of side effects 

 

If you get any side effects, talk to your doctor or pharmacist. 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 Ritonavir Mylan 
 

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

 

Do not use this medicine after the expiry date on the carton or bottle label after ‘EXP’. The expiry 

date refers to the last day of that month. 

 

After first opening, use within 100 days. 

 

Do not store above 30C. Store in the original bottle in order to protect from moisture. 

 

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

you no longer use. These measures will help the environment. 

 

 

6. Contents of the pack and other information 
 

What Ritonavir Mylan contains 

 

- The active substance is ritonavir. Each film-coated tablet contains 100 mg ritonavir. 
- The other tablet ingredients are: copovidone, sorbitan laurate, colloidal anhydrous silica, 

sodium chloride, sodium stearyl fumarate see section 2 ‘Ritonavir Mylan contains sodium’. 

- The tablet coating is composed of: hypromellose, titanium dioxide (E171), macrogols, 
hydroxypropylcellulose, talc, iron oxide yellow (E172), colloidal anhydrous silica, polysorbate 

80. 

 

What Ritonavir Mylan looks like and contents of the pack 

 

Ritonavir Mylan film-coated tablets are yellow, capsule shaped and marked with ‘M163’ on one side 

and plain on the other. 

 

Ritonavir Mylan film-coated tablets are available in plastic bottles with screw caps containing 30, 90 

or 100 tablets and in multipacks of 90 tablets comprising 3 bottles, each containing 30 tablets. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

 

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

 

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


59 

Manufacturer 

Generics [UK] Limited,  

Station Close, Potters Bar, Hertfordshire,  

EN6 1TL, United Kingdom 

 

McDermott Laboratories Limited trading as Gerard Laboratories trading as Mylan Dublin, 

Unit 35/36 Baldoyle Industrial Estate, 

Grange Road, Dublin 13, 

Ireland 

 

Mylan Hungary Kft, 

Mylan utca 1, Komárom, H-2900 

Hungary 

 

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 

 



60 

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} 

 

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. 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
	A. LABELLING
	B. PACKAGE LEAFLET