Pravafenix

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ANNEX I 
  

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 40 mg pravastatin sodium and 160 mg fenofibrate. 
 
Excipient(s) with known effect:  
Each hard capsule contains 19 mg of lactose monohydrate.  
 
For the full list of excipients, see section 6.1. 

 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule. 
 
Hard capsule, with light green body and olive cap, containing a waxy white beige mass and a tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Pravafenix is indicated as an adjunct to diet and other non-pharmacological treatment (e.g. exercise, 
weight reduction) for the treatment of mixed hyperlipidaemia in adult patients at high cardiovascular 
risk to reduce triglycerides and increase HDL-C when LDL-C levels are adequately controlled while 
on a treatment with pravastatin 40 mg monotherapy. 
 
4.2 Posology and method of administration 
 
Prior to initiating Pravafenix, secondary causes of combined dyslipidaemia should be excluded and 
patients should be placed on a standard cholesterol and triglycerides-lowering diet which should be 
continued during treatment. 
 
Posology 
The recommended dose is one capsule per day. Dietary restrictions instituted before therapy should be 
continued. 
 
Response to therapy should be monitored by determination of serum lipid values. Rapid reduction of 
serum lipid levels usually follows Pravafenix treatment, but treatment should be discontinued if an 
adequate response has not been achieved within three months. 
 
Special populations 
Elderly patients (≥ 65 years old) 
Treatment initiation with Pravafenix should be decided after renal function has been evaluated (see 
section 4.4 Renal and urinary disorders). Limited safety data on Pravafenix is available in patients >75 
years of age and care should be exercised.  
 
Renal impairment 
 
Pravafenix is contraindicated in patients with moderate to severe renal impairment (defined as a 
creatinine clearance < 60 ml/min) (see section 4.3.) 
No modification of posology should be necessary in patients with mild renal impairment. 



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Hepatic impairment 
Pravafenix is not recommended in patients with moderate hepatic impairment and is contraindicated in 
patients with severe hepatic impairment (see section 4.3.). No posology adjustment is required in 
patients with mild hepatic impairment. 
 
Paediatric population (< 18 years old) 
There is no relevant use of Pravafenix in the paediatric population (< 18 years old) for the indication 
of mixed dyslipidaemia (see section 4.3). 
 
Method of administration 
Oral use. 
The recommended dose is one capsule taken daily during the evening meal. Since it is less well 
absorbed from an empty stomach, Pravafenix should always be taken with food (see sections 4.5. and 
5.2).  
 
4.3 Contraindications  
 
- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
- Severe hepatic impairment including biliary cirrhosis or active liver disease including unexplained 

persistent elevations in liver function tests (including serum transaminase elevation) exceeding 3 
fold the upper limit of normal (ULN) (see section 4.4). 

- Children and adolescents (age below 18 years). 
- Moderate to severe renal impairment (defined as an estimated creatinine clearance < 60 ml/min).  
- Known photo allergy or photo toxic reaction during treatment with fibrates or ketoprofen. 
- Gallbladder disease (see section 4.4). 
- Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe 

hypertriglyceridaemia (see section 4.4). 
- Pregnancy and breast-feeding (see section 4.6). 
- Personal history of myopathy and/or rhabdomyolysis with statins and/or fibrates or confirmed 

creatine phosphokinase (CK) elevation above 5 times the ULN under previous statin treatment 
(see section 4.4). 

 
4.4 Special warnings and precautions for use 
 
The pharmacokinetics properties of Pravafenix are not completely identical to the co-administration of 
the existing monotherapies when taken with fat-meal or in fasting state. Patients should not be 
switched from a free co-administration of fenofibrate and pravastatin preparation to Pravafenix (see 
section 5.2.). 
 
Musculoskeletal and connective tissue disorders  
As with other lipid lowering substances, pravastatin or fenofibrate have been associated with the onset 
of myalgia, myopathy and very rarely rhabdomyolysis with or without secondary renal insufficiency. 
Rhabdomyolysis is an acute potentially fatal condition of skeletal muscle, which may develop at any 
time during treatment and is characterised by massive muscle destruction associated with major 
increase in CK (usually > 30 or 40 times the ULN) leading to myoglobinuria.  
 
The risk of muscle toxicity is increased when a fibrate and a 3-hydroxy-3-methyl-glutaryl-
Coenzyme A (HMG-CoA) reductase inhibitor are administered together. Myopathy must be 
considered in any patient presenting with unexplained muscle symptoms such as pain or tenderness, 
muscle weakness, or muscle cramps. In such cases CK levels should be measured (see below).  
 
Consequently, the potential benefit/risk ratio of Pravafenix should be closely assessed before treatment 
initiation and patients should be monitored for any signs of muscle toxicity. Certain predisposing 
factors such as age > 70, renal impairment, hepatic impairment, hypothyroidism, personal history of 
muscular toxicity with a statin or fibrate, personal or familial history of hereditary muscular disorders 



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or alcohol abuse may increase the risk of muscular toxicity and therefore CK measurement is indicated 
before starting the combination therapy in these patients (see below). 
 
Statins including pravastatin must not be co-administered with systemic formulations of fusidic acid or 
within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is 
considered essential, statin treatment should be discontinued throughout the duration of fusidic acid 
treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving 
fusidic acid and statins in combination (see section 4.5). The patient should be advised to seek medical 
advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.  
Statin therapy may be re-introduced seven days after the last dose of fusidic acid.  
In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment 
of severe infections, the need for co-administration of Pravafenix and fusidic acid should only be 
considered on a case by case basis and under close medical supervision.  
Before treatment initiation  
CK levels should be measured prior to initiation of therapy. The baseline CK levels may also be useful 
as a reference in the event of a later increase during the combination therapy. When measured, CK 
levels should be interpreted in the context of other potential factors that can cause transient muscle 
damage, such as strenuous exercise or muscle trauma and repeated if necessary.  
 
If CK levels are significantly elevated > 5 times the ULN at baseline, the results should be controlled 
after 5-7 days. If confirmed, the treatment should definitively not be initiated (see section 4.3).  
 
During treatment 
Routine monitoring of CK is systematically recommended every 3 months during the first 12 months 
of the combination therapy and let to the appreciation of the clinician beyond this initial period.  
Patients should be advised to report promptly unexplained muscle pain, tenderness, weakness or 
cramps. In these cases, CK levels should be measured.  
 
If a markedly elevated (> 5 times the ULN) CK level is detected and confirmed, Pravafenix therapy 
must be discontinued. Treatment discontinuation should also be considered if the muscular symptoms 
are severe and cause daily discomfort (whatever CK levels). If a hereditary muscular disease is 
suspected in such patients, restarting Pravafenix therapy is not recommended. 
 
There have been very rare reports of an immune-mediated necrotizing myopathy (IMNM) during or 
after treatment with some statins. IMNM is clinically characterized by persistent proximal muscle 
weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment. 
 
Hepatobiliary disorders  
As with other lipid lowering medicinal products, moderate increases in transaminase levels have been 
reported in some patients treated with pravastatin or fenofibrate. In the majority of cases, liver 
transaminase levels have returned to their baseline value without the need for treatment 
discontinuation.  
It is recommended that transaminase levels be monitored every 3 months during the first 12 months of 
treatment and let to the appreciation of the clinician beyond this initial period.  
Special attention should be paid to patients who develop increase in transaminase levels and therapy 
should be discontinued if increases in aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) exceed 3 times the ULN and persist. 
Caution should be exercised when Pravafenix is administered to patients with a history of liver disease 
or heavy alcohol ingestion. 
 
Pancreatitis 
Pancreatitis has been reported in patients taking fenofibrate or pravastatin (see sections 4.3). This 
occurrence may represent a failure of efficacy in patients with severe hypertriglyceridaemia, a direct 
medicinal product effect, or a secondary phenomenon mediated through biliary tract stone or sludge 
formation, resulting in the obstruction of the common bile duct. 
 



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Renal and urinary disorders 
Pravafenix is contraindicated in moderate to severe renal impairment (section 4.3). 
It is recommended to systematically assess the estimated creatinine clearance at the initiation of the 
treatment and every 3 months during the first 12 months of the combination therapy then let to the 
appreciation of the clinician beyond this period.  
 
Treatment should be discontinued in case of an estimated creatinine clearance < 60 ml/min. 
 
Interstitial lung disease 
Exceptional cases of interstitial lung disease have been reported with some statins, especially with 
long term therapy (see section 4.8). Presenting features can include dyspnoea, non-productive cough 
and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has 
developed interstitial lung disease, Pravafenix therapy should be discontinued. 
 
Cholelithiasis 
Fenofibrate may increase cholesterol excretion into the bile, potentially leading to cholelithiasis. If 
cholelithiasis is suspected, gallbladder studies are indicated. Pravafenix should be discontinued if 
gallstones are found.  
 
Venothromboembolic events 
In the FIELD study, a statistically significant increase was reported in the incidence of pulmonary 
embolism (0.7% in the placebo group versus 1.1% in the fenofibrate group; p=0.022) and a 
statistically non significant increase in deep vein thrombosis (placebo 1.0% 48/4,900 patients) versus 
fenofibrate 1.4% (67/4,895); p=0.074. The increased risk of venous thrombotic events may be related 
to the increased homocysteine level, a risk factor for thrombosis and other unidentified factors. The 
clinical significance of this is not clear. Therefore, caution should be exercised in patients with history 
of pulmonary embolism.   
 
Diabetes Mellitus 
Some evidence suggests that statins as a class raise blood glucose and in some patients, at high risk of 
future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. 
This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should 
not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, 
BMI>30kg/m 2, raised triglycerides, hypertension) should be monitored both clinically and 
biochemically according to national guidelines. 
 
Concomitant use with glecaprevir/pibrentasvir 
The use of Pravafenix is not recommended in patients treated with glecaprevir/pibrentasvir. 
Concomitant use of pravastatin and glecaprevir/pibrentasvir may increase the plasma concentration of 
pravastatin and may lead to an increase of dose-dependent adverse events including myopathy risk. 
Patients treated with glecaprevir/pibrentasvir should not exceed 20 mg per day of pravastatin. 
 
Lactose 
This medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
There have been no formal interaction studies for Pravafenix; however the concomitant use of the 
active substances in patients in clinical studies has not resulted in any unexpected interactions. The 
following statements reflect the information available on the individual active substances (fenofibrate 
and pravastatin). 
 
Interactions relevant to pravastatin  
Colestyramine/Colestipol 



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Concomitant administration resulted in approximately 40 to 50% decrease in the bioavailability of 
pravastatin. There was no clinically significant decrease in bioavailability or therapeutic effect when 
pravastatin was administered one hour before or four hours after colestyramine or one hour before 
colestipol.  
 
Ciclosporin 
Concomitant administration of pravastatin and ciclosporin leads to an approximately 4 fold increase in 
pravastatin systemic exposure. In some patients, however, the increase in pravastatin exposure may be 
larger. Clinical and biochemical monitoring of patients receiving this combination is recommended. 
 
Medicinal products metabolised by cytochrome P450 
Pravastatin is not metabolised to a clinically significant extent by the cytochrome P450 system. This is 
why medicinal products that are metabolised by, or are inhibitors of, the cytochrome P450 system can 
be added to a stable regimen of pravastatin without causing significant changes in the plasma levels of 
pravastatin, as have been seen with other statins. The absence of a significant pharmacokinetic 
interaction with pravastatin has been specifically demonstrated for several medicinal products, 
particularly those that are substrates/inhibitors of CYP3A4 e.g. diltiazem, verapamil, itraconazole, 
ketoconazole, protease inhibitors, grapefruit juice and CYP2C9 inhibitors (e.g. fluconazole).  
 
In one of two interaction studies with pravastatin and erythromycin a statistically significant increase 
in the area under the curve (AUC) (70%) and Cmax (121%) of pravastatin was observed. In a similar 
study with clarithromycin a statistically significant increase in AUC (110%) and Cmax (127%) was 
observed. Although these changes were minor, caution should be exercised when associating 
pravastatin with erythromycin or clarithromycin.  
 
Fusidic acid 
The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration 
of systemic fusidic acid with statins. The mechanism of this interaction (whether it is 
pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of 
rhabdomyolysis (including some fatalities) in patients receiving this combination.  
If treatment with systemic fusidic acid is necessary, pravastatin treatment should be discontinued 
throughout the duration of the fusidic acid treatment. Also see section 4.4.  
Glecaprevir/pibrentasvir 
Concomitant use of pravastatin and glecaprevir/pibrentasvir may increase the plasma concentration of 
pravastatin and may lead to an increase of dose-dependent adverse events including myopathy risk. 
Patients treated with glecaprevir/pibrentasvir should not exceed 20 mg per day of pravastatin. 
Therefore Pravafenix is not recommended in those patients. 
 
Other medicinal products 
In interaction studies, no statistically significant differences in bioavailability were observed when 
pravastatin was administered with acetylsalicylic acid, antacids (when given one hour prior to 
pravastatin), nicotinic acid or probucol. 
 
Interactions relevant to fenofibrate 
Bile acid resin 
Bile acid binding resins frequently reduce the absorption of medicinal products and when resins are 
being co-administered, fenofibrate should be taken 1 hour before, or 4 to 6 hours after, the resin so as 
not to impede the absorption of fenofibrate. 
 
Oral anticoagulants 
Fenofibrate enhances oral anticoagulant effect and may increase risk of bleeding. It is recommended 
that the dose of anticoagulants is reduced by about one third at the start of treatment and then 
gradually adjusted if necessary according to INR (International Normalised Ratio) monitoring. This 
combination is, therefore, not recommended.  
 
Ciclosporin 



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Some severe cases of reversible renal function impairment have been reported during concomitant 
administration of fenofibrate and ciclosporin. The renal function of these patients must therefore be 
closely monitored and the treatment with fenofibrate stopped in the case of severe alteration of 
laboratory parameters. 
 
Food interaction 
Pravafenix must be taken with food, as food enhances the bioavailability of fenofibrate (see sections 
4.2 and 5.2). 
 
In all clinical trials, patients were instructed to take Pravafenix daily during the evening meal and 
dietary restrictions instituted before therapy should be continued. Since current safety and efficacy 
data are based upon administration with food and with dietary restrictions, it is recommended that 
Pravafenix is administered with food. (see sections 4.2 and 5.2). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Pravafenix 
There are no data from the combined use of pravastatin and fenofibrate in pregnant women. The 
combination has not been tested in reproductive toxicity studies. The potential risk for humans is 
unknown. Therefore, as far as pravastatin is contra indicated (see below), Pravafenix is contraindicated 
during pregnancy (see section 4.3). 
 
Pravastatin sodium 
Pravastatin is contraindicated during pregnancy and should be administered to women of childbearing 
potential only when such patients are unlikely to conceive and have been informed of the potential 
risk. Special caution is recommended in women of childbearing potential to ensure proper 
understanding of the potential risk associated with pravastatin therapy during pregnancy. If a patient 
plans to become pregnant or becomes pregnant, the physician has to be informed immediately and 
pravastatin should be discontinued because of the potential risk to the foetus. 
 
Fenofibrate 
There are no data from the use of fenofibrate in pregnant women. Animal studies have not 
demonstrated any teratogenic effects. Embryotoxic effects have been shown at doses in the range of 
maternal toxicity (see section 5.3). The potential risk for humans is unknown. 
 
Breastfeeding 
Pravafenix 
No studies in lactating animals have been conducted with Pravafenix. Therefore, taking into account 
the contra indication of pravastatin during lactation, Pravafenix is contraindicated during breastfeeding 
(see section 4.3). 
 
Pravastatin sodium 
A small amount of pravastatin is excreted in human breast milk; therefore pravastatin is 
contraindicated during breastfeeding (see section 4.3). 
 
Fenofibrate 

Fenofibrate is excreted in milk of female rat. 
There are no data on the excretion of fenofibrate and/or its metabolites into human breast milk. 
 
Fertility 

No effect on fertility in reproductive toxicity studies have been observed with both fenofibrate and 
pravastatin (see section 5.3) 
There are no data on fertility from the combined use of fenofibrate and pravastatin  
 



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4.7 Effects on ability to drive and use machines 
 
Pravafenix has no or negligible influence on the ability to drive and use machines. However, when 
driving vehicles or using machines, it should be taken into account that dizziness and visual 
disturbances may occur during treatment. 
 
4.8 Undesirable effects  
 
Summary of the safety profile 
The most commonly reported adverse reactions (ADRs) during Pravafenix therapy are increased 
transaminase and gastrointestinal disorders. 
 
Tabulated list of adverse reactions 
In clinical trials, over 1,566 patients received Pravafenix. Adverse reactions have usually been mild 
and transient. 
 
The frequencies of adverse reactions are ranked according to the following: Very common (≥ 1/10), 
Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very 
rare (< 1/10,000). 
 
System organ class Adverse reaction Frequency 
Immune system 
disorders 

Hypersensitivity reactions  Uncommon 

Metabolism and 
nutrition disorders 

Diabetes mellitus aggravated, Obesity Uncommon 

Psychiatric disorders Sleep disturbance including insomnia and nightmares Uncommon 

Nervous system 
disorders 

Dizziness, headache, paraesthesia Uncommon 

Cardiac disorders Palpitations Uncommon 
Gastrointestinal 
disorders 

Abdominal distension, abdominal pain, abdominal pain upper, 
constipation, diarrhoea, dry mouth, dyspepsia, eructation, 
flatulence, nausea, abdominal discomfort, vomiting. 

Common 

Hepatobiliary disorders Transaminases increased. Common 
Hepatic pain, gammaglutamyl transferase increased. Uncommon 

Skin and subcutaneous 
tissue disorders 

Pruritus, urticaria Uncommon 

Musculoskeletal, 
connective tissue and 
bone disorders 

Arthralgia, back pain, blood creatine phosphokinase increased, 
muscle spasms, musculoskeletal pain, myalgia, pain in extremity.  

Uncommon 

Renal and urinary 
disorders 

Blood creatinine increased, creatinine renal clearance decreased, 
creatinine renal clearance increased, Renal failure 

Uncommon 

General disorders and 
administration site 
conditions 

Asthenia, fatigue, influenza like illness Uncommon 

Investigation Blood cholesterol increased, blood triglycerides increased, low-
density lipoprotein increased, weight increased. 

Uncommon 

 
Description of selected adverse reactions 
 
Skeletal muscle: Marked and persistent increases of creatine phosphokinase (CK) have been reported 
infrequently. In clinical studies, the incidence of important elevations in creatine phosphokinase (CK ≥ 



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3 times the ULN, < 5 times the ULN) was 1.92% for patients treated with Pravafenix. Clinically 
important elevations in creatine phosphokinase (CK ≥ 5 times the ULN, < 10 times the ULN without 
muscular symptoms) were seen in 0.38% of the patients treated with Pravafenix. Clinically important 
elevation (CK ≥ 10 times the ULN without muscular symptoms) was seen in 0.06% of the patients 
treated with Pravafenix. (see section 4.4). 
 
Liver reactions: Marked and persistent increases of serum transaminases have been reported 
infrequently. In clinical studies, the incidence of important elevations in serum transaminases (ALT 
and/or AST ≥ 3 times the ULN, < 5 times the ULN) was 0.83% for patients treated with Pravafenix. 
Clinically important elevations in serum transaminases (ALT and/or AST ≥ 5 times the ULN) were 
seen in 0.38% of the patients treated with Pravafenix. (see section 4.4). 
 
Additional information on the individual active substances of the fixed dose combination 
Pravafenix contains pravastatin and fenofibrate. Additional adverse reactions associated with the use 
of medicinal products containing pravastatin or fenofibrate observed in clinical trials and post-
marketing experience that may potentially occur with Pravafenix are listed below. Frequency 
categories are based on information available from pravastatin and fenofibrate Summary of Product 
characteristics available in the EU. 
 
System Organ Class Adverse reaction 

(fenofibrate) 
Adverse reaction 

(Pravastatin) 
Frequency 

Blood and lymphatic 
system disorders 

Haemoglobin decreased, 
White blood cell count 
decreased 

 Rare 

Nervous system 
disorders 

Fatigue and vertigo  Rare 

 Peripheral polyneuropathy Very Rare 

Eye disorders  
 

 Vision disturbance (including 
blurred vision and diplopia)  

Uncommon 

Vascular disorders Thromboembolism 
(pulmonary embolism, deep 
vein thrombosis)* 

 Uncommon 

Respiratory, thoracic 
and mediastinal 
disorders 

Intersticial pneumopathies  Not known 

Hepatobiliary disorders Cholelithiasis  Uncommon 

 Jaundice, fulminant hepatic 
necrosis, hepatitis 

Very rare 

Jaundice, complications of 
cholelithiasis (e.g 
cholecystitis, cholangitis, 
biliary colic, etc). 

 Not known 

Skin and subcutaneous 
tissue disorders 

 Skin rash, Scalp/hair abnormality 
(including alopecia)  

Uncommon 

 Dermatomyositis Very rare 
Alopecia, photosensitivity 
reactions 

 Rare 

 Lichenoid eruption Not known 
Musculoskeletal, 
connective tissue and 
bone disorders 

Muscle disorder (e.g. 
myositis, muscular 
weakness) 

 Uncommon 

 Rhabdomyolysis, which can be 
associated with acute renal failure 

Very rare 



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secondary to myoglobinuria, 
myopathy (see section 4.4); 
myositis, polymyositis. Isolated 
cases of tendon disorders, 
sometimes complicated by 
rupture. Erythematous lupus like 
syndrome. 

Rhabdomyolysis Immune-mediated necrotizing 
myopathy (see section 4.4). 

Not known 

Renal and urinary 
disorders:  

 Abnormal urination (including 
dysuria, frequency, nocturia) 

Uncommon 

Reproductive system 
and breast disorders 

Sexual dysfunction Sexual dysfunction  Uncommon 

General disorders:   Fatigue  Uncommon 
Investigations Blood urea increased  Rare 
* In the FIELD-study (fenofibrate study), a randomised placebo-controlled trial performed in 9,795 
patients with type 2 diabetes mellitus, a statistically significant increase in pancreatitis cases was 
observed in patients receiving fenofibrate versus patients receiving placebo (0.8% versus 0.5%; p = 
0.031). In the same study, a statistically significant increase was reported in the incidence of 
pulmonary embolism (0.7% in the placebo group versus 1.1% in the fenofibrate group; p = 0.022) and 
a statistically non-significant increase in deep vein thromboses (placebo: 1.0 % [48/4,900 patients] 
versus fenofibrate 1.4% [67/4,895 patients]; p = 0.074). 
 
The following adverse events have been reported with some statins: 
- Nightmares 
- Memory loss 
- Depression 
- Exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4). 
- Diabetes Mellitus: Frequency will depend on the presence or absence of risk factors (fasting blood 

glucose ≥ 5.6 mmol/L, BMI>30kg/m2, raised triglycerides, history of hypertension). 
 
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 
 
In the event of an overdose, symptomatic and supportive measures should be employed. 
 
Pravastatin 
Reported cases of overdose were asymptomatic and did not give rise to abnormal laboratory tests. No 
specific antidote is known. If overdose is suspected, treat symptomatically and institute appropriate 
supportive measures as required.  
 
Fenofibrate 
No specific antidote is known. If an overdose is suspected, treat symptomatically and institute 
appropriate supportive measures as required. Fenofibrate cannot be eliminated by haemodialysis.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 

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Pharmacotherapeutic group: Lipid modifying agents, HMG CoA reductase inhibitors in combination 
with other lipid modifying agents, ATC code: C10BA03 
 
Pharmacodynamic effects 
 
Pravafenix contains fenofibrate and pravastatin, which have different modes of action and show 
additive effects in terms of reduction of serum lipid. The following statements reflect the 
pharmacodynamic/pharmacokinetic properties of the individual active substances of Pravafenix. 
 
Fenofibrate 
Fenofibrate is a fibric acid derivative whose lipid modifying effects reported in humans are mediated 
via activation of Peroxisome Proliferator Activated Receptor type alpha (PPARα). Studies with 
fenofibrate on lipoprotein fractions show decreases in levels of LDL and VLDL cholesterol. HDL 
cholesterol levels are frequently increased. LDL and VLDL triglycerides are reduced. The overall 
effect is a decrease in the ratio of low and very low-density lipoproteins to high-density lipoproteins. 
 
The lipid-lowering properties of fenofibrate seen in clinical practice have been explained in vivo in 
transgenic mice and in human hepatocyte cultures by activation of Peroxisome Proliferator Activated 
Receptor type α (PPARα). Through this mechanism, fenofibrate increases lipolysis and elimination of 
triglyceride rich particles from plasma by activating lipoprotein lipase and reducing production of 
Apoprotein C-III. Activation of PPARα also induces an increase in the synthesis of Apoproteins A-I, 
A-II and of HDL cholesterol.  
 
There is evidence that treatment with fibrates may reduce coronary heart disease events but they have 
not been shown to decrease all cause mortality in the primary or secondary prevention of 
cardiovascular disease.  
 
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial was a randomized 
placebo-controlled study of 5,518 patients with type 2 diabetes mellitus treated with fenofibrate in 
addition to simvastatin. Fenofibrate plus simvastatin therapy did not show any significant differences 
compared to simvastatin monotherapy in the composite primary outcome of non-fatal myocardial 
infarction, non-fatal stroke, and cardiovascular death (hazard ratio [HR] 0.92, 95% CI 0.79-1.08, p = 
0.32 ; absolute risk reduction: 0.74%). In the pre-specified subgroup of dyslipidaemic patients, defined 
as those in the lowest tertile of HDL-C (≤34 mg/dl or 0.88 mmol/L) and highest tertile of TG (≥204 
mg/dl or 2.3 mmol/L) at baseline, fenofibrate plus simvastatin therapy demonstrated a 31% relative 
reduction compared to simvastatin monotherapy for the composite primary outcome (hazard ratio 
[HR] 0.69, 95% CI 0.49-0.97, p = 0.03 ; absolute risk reduction: 4.95%). Another prespecified 
subgroup analysis identified a statistically significant treatment-by-gender interaction (p = 0.01) 
indicating a possible treatment benefit of combination therapy in men (p=0.037) but a potentially 
higher risk for the primary outcome in women treated with combination therapy compared to 
simvastatin monotherapy (p=0.069). This was not observed in the aforementioned subgroup of patients 
with dyslipidaemia but there was also no clear evidence of benefit in dyslipidaemic women treated 
with fenofibrate plus simvastatin, and a possible harmful effect in this subgroup could not be 
excluded. 
 
Plasma uric acid levels are increased in approximately 20% of hyperlipidaemic patients, particularly in 
those with type IV disease. Fenofibrate has a uricosuric effect and is therefore of additional benefit in 
such patients.  
 
Pravastatin 
Pravastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 
reductase, the enzyme catalysing the early rate-limiting step in cholesterol biosynthesis, and produces 
its lipid-lowering effect in two ways. Firstly, with the reversible and specific competitive inhibition of 
HMG-CoA reductase, it effects modest reduction in the synthesis of intracellular cholesterol. This 
results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated 
catabolism and clearance of circulating LDL-cholesterol. 



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Secondly, pravastatin inhibits LDL production by inhibiting the hepatic synthesis of VLDL-
cholesterol, the LDL-cholesterol precursor. 
 
In both healthy subjects and patients with hypercholesterolaemia, pravastatin lowers the following 
lipid values: total cholesterol, LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides; 
while HDL-cholesterol and apolipoprotein A are elevated. 
 
Pravafenix 
The respective effects of pravastatin and fenofibrate are complementary. Pravastatin is more effective 
in reducing LDL-C and total cholesterol but presents only modest effects on TG and HDL-C while 
fenofibrate is very effective in decreasing TG and increasing HDL-C, but with few effects on LDL-C.  
 Additionally, fibrates have the properties to modify the size and density of LDL-C particles to make 
them less atherogenic. 
Fibrates and statins in combination have also been shown to synergistically increase the transcriptional 
activities of PPARα receptors. 
 
Clinical efficacy and safety  
 
Four multicenter studies with either Pravafenix 40 mg/160 mg or Pravastatin 40 mg or Simvastatin 
20 mg were conducted: 3 studies included a 12 week randomized, double-blind, active controlled 
period with an open-label extension phase and one was a 24-week open-label study.  
In total, these studies enrolled 1,637 patients who have not had an adequate response to treatment with 
pravastatin 40 mg monotherapy or simvastatin 20 mg in Europe and in the USA.  
 
In the pivotal European multicenter 64-week clinical trial including 12 week randomised, double-
blind, double-dummy, 2-arm, parallel study period, 248 high vascular risk patients with mixed 
dyslipidaemia were randomised to one of the two treatment groups: Pravafenix 40 mg/160 mg or 
pravastatin 40 mg. Only patients who had not met their NCEP ATP III target LDL-C and Triglyceride 
goals (LDL >100 mg/dl and TG >150 mg/dl) after 8 weeks on pravastatin 40 mg (1 tablet, once daily) 
were randomized. Patients receiving Pravafenix 40 mg/160 mg were compared to those receiving 
pravastatin 40 mg: Pravafenix significantly lowered non-HDL-C, LDL-C, TG and significantly 
increased HDL-C to a greater extent than pravastatin 40 mg (table). 
 

Mean percent changes from baseline to week 12 
for patients treated with Pravafenix  40 mg/160 mg or Pravastatin 40 mg once daily 

 

 

Pravafenix  
40 mg/160 mg 

Na = 120 
PRAVASTATIN 40 mg 

Na = 119 
Pravafenix  versus 
PRAVASTATIN 

Mean (%)± SEb Mean (%)± SEb p-valuec 
Non-HDL-C 
(mg/dl) -14.1 ± 1.78 -6.1 ± 1.79 0.0018 

LDL-C (mg/dl) -11.7 ± 1.75 -5.9 ± 1.76 0.019 
HDL-C (mg/dl) +6.5 ± 1.12 +2.3 ± 1.13 0.0089 
TG (mg/dl) -22.6 ± 4.37 -2.0 ± 4.39 0.0010 
TC (mg/dl) -9.9 ± 1.37 -4.4 ± 1.38 0.006 
Apo A1 (g/L) +5.5 ± 0.99 +2.8 ± 0.97 0.058 
Apo B (g/L) -12.6 ± 1.57 -3.8 ± 1.53 <0.0001 
Apo B/Apo A1 -16.3 ± 1.66 -6.0 ± 1.61 <0.0001 
Fibrinogen (g/L) -8.8 ± 1.80 +1.4 ± 1.75 <0.0001 
Hs-CRP (mg/L) -1.1 ± 0.61 +0.6 ± 0.70 0.003 



13 
 

a Number of patients 
b Mean percent change (least square mean ± standard error) between baseline measured after 8 
weeks on Pravastatin 40 mg and 12 additional weeks with Pravafenix  40 mg/160 mg or 
Pravastatin 40 mg 
c Pairwise p-value is significant if <0.05 
 
The effects of Pravafenix 40 mg/160 mg were confirmed in a similar multicenter, 64-week trial 
including a 12 week randomized, double-blind phase in a study performed in the USA and comparing 
Pravafenix 40 mg/160 mg to Fenofibrate 160 mg monotherapy and Pravastatin 40 mg monotherapy in 
patients with mixed dyslipidaemia. The incremental benefit of Pravafenix 40 mg/160 mg on main lipid 
parameters versus Pravastatin 40 mg and Fenofibrate 160 mg monotherapy was also established. 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Pravafenix in all subsets of the paediatric population in disorders of lipoprotein metabolism and other 
hyperlipidaemias (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
No clinically significant pharmacokinetic interaction was seen when fenofibrate was coadministered 
with pravastatin. 
 
Absorption 
 
Pravafenix is bioequivalent to coadministered fenofibrate and pravastatin in a single dose study. 
However in a multiple dose study, the results showed that the product is not bioequivalent because its 
bioavailability after multiple dosing is a 20% lower for the fenofibrate component of the combination. 
This is due to the fat content of the meal.  
Therefore the fixed dose combination (Pravafenix) could not be considered interchangeable with the 
free co-administration of fenofibrate and pravastatin mono-component drug products. 
 
A pharmacokinetic study after a single dose administration of Pravafenix has been performed in fed 
and fasting condition. The results of this study show that food has effect on the rate and extent of 
absorption in the fixed dose combination. The bioavailability of fenofibric acid is lower in fasting 
conditions after a single dose administration of the Fenofibrate-Pravastatin 160/40 mg combination. 
The decreased in AUCt, AUC∞ and Cmax of fenofibric acid (point estimate) is of 30.94%, 10.9% and 
68.71% respectively.  

The bioavailability of pravastatin is higher after a single dose administration of the test product 
Fenofibrate/Pravastatin 160/40 mg in fasting conditions than after a single dose of the product in fed 
conditions. The increase in AUC∞, AUCt, and Cmax is of 111.88%, 114.06%, and 115.28% 
respectively. In line with several formulations for fenofibrate, the fixed combination is recommended 
to be taken with food because the bioavailability of fenofibrate is increased when administered with 
food and the lipid-lowering efficacy of pravastatin is not altered.  

 
Pravastatin  
 
Pravastatin is administered orally in the active form. It is rapidly absorbed; peak serum levels are 
achieved 1 to 1.5 hours after ingestion. On average, 34% of the orally administered dose is absorbed, 
with an absolute bioavailability of 17%.  
 
The presence of food in the gastrointestinal tract leads to a reduction in the bioavailability, but the 
cholesterol-lowering effect of pravastatin is identical whether taken with or without food. 
 



14 
 

After absorption, 66% of pravastatin undergoes a first-pass extraction through the liver, which is the 
primary site of its action and the primary site of cholesterol synthesis and clearance of LDL-
cholesterol. In vitro studies demonstrated that pravastatin is transported into hepatocytes and with 
substantially less intake in other cells. In view of this substantial first pass through the liver, plasma 
concentrations of pravastatin have only a limited value in predicting the lipid-lowering effect. 
The plasma concentrations are proportional to the doses administered. 
 
Fenofibrate 
 
Maximum plasma concentrations (Cmax) occur within 4 to 5 hours after oral administration. Plasma 
concentrations are stable during continuous treatment in any given individual. 
The absorption of fenofibrate is increased when administered with food. The food effect increases with 
the fat content: the larger the lipid content the larger the bioavailability of fenofibrate. 
 
Distribution 
 
Pravastatin  
About 50% of circulating pravastatin is bound to plasma proteins. The volume of distribution is about 
0.5 l/kg. A small quantity of pravastatin passes into the human breast milk. 
 
Fenofibrate 
Fenofibric acid is strongly bound to plasma albumin (more than 99%). 
 
Biotransformation and elimination 
 
Pravastatin 
Pravastatin is not significantly metabolised by cytochrome P450 nor does it appear to be a substrate or 
an inhibitor of P-glycoprotein but rather a substrate of other transport proteins. 
Following oral administration, 20% of the initial dose is eliminated in the urine and 70% in the faeces. 
Plasma elimination half-life of oral pravastatin is 1.5 to 2 hours. 
After intravenous administration, 47% of the dose is eliminated by the renal excretion and 53% by 
biliary excretion and biotransformation. The major degradation product of pravastatin is the 3-α-
hydroxy isomeric metabolite. This metabolite has one-tenth to one-fortieth the HMG-CoA reductase 
inhibitor activity of the parent compound. 
The systemic clearance of pravastatin is 0.81 l/h/kg and the renal clearance is 0.38 l/h/kg indicating 
tubular secretion. 
 
Fenofibrate 
No unchanged fenofibrate can be detected in the plasma where the principal metabolite is fenofibric 
acid. The drug is excreted mainly in the urine. Practically all the drug is eliminated within 6 days. 
Fenofibrate is mainly excreted in the form of fenofibric acid and its glucuronide conjugate. In elderly 
patients, the fenofibric acid apparent total plasma clearance is not modified. The plasma elimination 
half-life of fenofibric acid is approximately 20 hours. 
 
Kinetic studies following the administration of a single dose and continuous treatment have 
demonstrated that the drug does not accumulate. Fenofibric acid is not eliminated by haemodialysis. 
 
5.3 Preclinical safety data 
 
The safety of concomitant administration of pravastatin and fenofibrate was assessed in rats. 
Toxicological findings in these co-administration studies were consistent with those seen with 
pravastatin and fenofibrate administered individually.  
 
Pravastatin 



15 
 

Based on conventional studies of safety pharmacology, repeated dose toxicity and toxicity on 
reproduction, there are no other risks for the patient than those expected due to the pharmacological 
mechanism of action.  
Repeated dose studies indicate that pravastatin may induce varying degrees of hepatotoxicity and 
myopathy; in general, substantive effects on these tissues were only evident at doses 50 or more times 
the maximum human mg/kg dose. In vitro and in vivo genetic toxicology studies have shown no 
evidence of mutagenic potential. In mice, a 2-year carcinogenicity study with pravastatin demonstrates 
at doses of 250 and 500 mg/kg/day (> 310 times the maximum human mg/kg dose), statistically 
significant increases in the incidence of hepatocellular carcinomas in males and females, and lung 
adenomas in females only. In rats a 2-year carcinogenicity study demonstrates at a dose of 
100 mg/kg/day (125 times the maximum human mg/kg/dose) a statistically significant increase in the 
incidence of hepatocellular carcinomas in males only. 
 
Fenofibrate 
Chronic toxicity studies have yielded no relevant information about specific toxicity of fenofibrate.  
Studies on mutagenicity of fenofibrate have been negative.  In rats and mice, liver tumours have been 
found at high dosages, which are attributable to peroxisome proliferation. These changes are specific 
to small rodents and have not been observed in other animal species. This is of no relevance to 
therapeutic use in man.  
Studies in mice, rats and rabbits did not reveal any teratogenic effect. Embryotoxic effects were 
observed at doses in the range of maternal toxicity. Prolongation of the gestation period and 
difficulties during delivery were observed at high doses. No sign of any effect on fertility has been 
detected. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
Lactose monohydrate 
Cellulose microcrystalline 
Ascorbyl palmitate 
Povidone K29-32 
Sodium starch glycolate 
Magnesium stearate 
Talc 
Triacetin 
Sodium hydrogen carbonate 
Lauroyl macrogolglycerides Type 1500 
Hydroxypropylcellulose 
Macrogol 20 000 
 
Capsule shell 
Gelatine 
Indigo carmine 
Black iron oxide 
Titanium dioxide 
Yellow iron oxide 
 
6.2 Incompatibilities 
 
Not applicable 
 
6.3 Shelf life 
 



16 
 

Polyamide-Aluminium-PVC/aluminium blister 
2 years. 
 
HDPE bottle 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Polyamide-Aluminium-PVC/aluminium blister packs containing 30, 60 and 90 hard capsules. 
Opaque white HDPE bottles containing 14, 30, 60 and 90 hard capsules. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Laboratoires SMB s.a. 
Rue de la Pastorale, 26-28 
B-1080 Brussels 
Belgium 
Tel. +32 (2) 411 48 28 
Fax. +32 (2) 411 28 28 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/679/001-007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 14 April 2011 
Date of latest renewal: 14 January 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 



17 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



18 
 

 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release: 
 
SMB Technology s.a. 
rue du Parc Industriel 39 
B-6900 Marche en Famenne 
Belgium 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 



19 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III  
LABELLING AND PACKAGE LEAFLET 



20 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
pravastatin/fenofibrate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 40 mg of pravastatin sodium and 160 mg of fenofibrate  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 hard capsules 
60 hard capsules 
90 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



22 
 

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 
 
Laboratoires SMB s.a. 
rue de la Pastorale, 26-28 
B-1080 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/679/001 30 hard capsules 
EU/1/11/679/002 60 hard capsules 
EU/1/11/679/003 90 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Pravafenix 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN  



23 
 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
Pravastatin/Fenofibrate  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
SMB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



24 
 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BOTTLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
pravastatin/fenofibrate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 40 mg of pravastatin sodium and 160 mg of fenofibrate. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 hard capsules 
30 hard capsules 
60 hard capsules 
90 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



25 
 

 
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 
 
Laboratoires SMB s.a. 
rue de la Pastorale, 26-28 
B-1080 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/679/007 14 hard capsules 
EU/1/11/679/004 30 hard capsules 
EU/1/11/679/005 60 hard capsules 
EU/1/11/679/006 90 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Pravafenix 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN  
NN  
 



26 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE FOR 14 AND 30 HARD CAPSULES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
Pravastatin/Fenofibrate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 40 mg of pravastatin sodium and 160 mg of fenofibrate. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 hard capsules 
30 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



27 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Laboratoires SMB s.a. 
rue de la Pastorale, 26-28 
B-1080 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/679/007 14 hard capsules 
EU/1/11/679/004 30 hard capsules 
 
 
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 
 
 



28 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLES FOR 60 AND 90 HARD CAPSULES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Pravafenix 40 mg/160 mg hard capsules 
Pravastatin/Fenofibrate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 40 mg of pravastatin sodium and 160 mg of fenofibrate. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 hard capsules 
90 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



29 
 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Laboratoires SMB s.a. 
rue de la Pastorale, 26-28 
B-1080 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/679/005 60 hard capsules 
EU/1/11/679/006 90 hard capsules 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



30 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



31 
 

Package leaflet: Information for the user 
 

Pravafenix 40 mg/160 mg hard capsules 
Pravastatin/Fenofibrate 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Pravafenix is and what it is used for 
2. What you need to know before you take Pravafenix 
3. How to take Pravafenix 
4. Possible side effects 
5. How to store Pravafenix 
6. Contents of the pack and other information 
 
 
1. What Pravafenix is and what it is used for 
 
Pravafenix contains two active substances: pravastatin and fenofibrate. Both are cholesterol/lipid 
modifying medicines.  
 
Pravafenix is used in addition to low fat diet in adults 
- To lower the level of your ‘bad’ cholesterol (LDL cholesterol). It does this by lowering the level 

of total cholesterol, and fatty substances called triglycerides in the blood.  
- To raise the level of your ‘good’ cholesterol (HDL cholesterol). 
 
What should I know about cholesterol and triglycerides? 
Cholesterol is one of several fats found in your blood. Your total cholesterol is made up mainly of 
LDL and HDL cholesterol.  
 
LDL cholesterol is often called ‘bad’ cholesterol because it can build up in the walls of your arteries 
and form plaque. Over time, this plaque build-up can lead to a clogging of your arteries. This clogging 
can slow or block blood flow to vital organs such as the heart and brain. When the blood flow is 
blocked, the result can be a heart attack or stroke.  
 
HDL cholesterol is often called ‘good’ cholesterol because it helps keep the ‘bad’ cholesterol from 
building up in the arteries and because it protects against heart disease.  
 
Triglycerides are another fat in your blood. They may raise your risk of having heart problems.  
 
In most people, there are no signs of cholesterol problems at first. Your doctor can measure your 
cholesterol with a simple blood test. Visit your doctor regularly to keep track of your cholesterol level.  
 
Pravafenix is used if you are an adult with an elevated risk for heart disease and need to improve 
cholesterol and triglycerides fat levels in your blood when your ‘bad’ cholesterol levels are being 
adequately controlled with pravastatin alone (a statin, a cholesterol-lowering medicine). 
 
 
2. What you need to know before you take Pravafenix 
 



32 
 

Do not take Pravafenix 
- if you are allergic to fenofibrate, pravastatin, or any of the other ingredients of this medicine 

(listed in section 6). 
- if you suffer from liver disease.  
- if you are under 18 years old. 
- if you suffer from kidney disease. 
- if you have had photoallergy (allergic reaction caused by sunlight or exposure to UV light) or 

phototoxic reactions (damage to skin caused by exposure to sunlight or UV light) during treatment 
with fibrates (lipid-modifying medicines) or ketoprofen (an anti-inflammatory medicine that can 
be used orally or on the skin for muscle and bone disorders, and orally for gout or period pain) 

- if you suffer from gallbladder disease. 
- if you suffer from pancreatitis (inflammation of the pancreas leading to abdominal pain) 
- if you are pregnant or breast-feeding. 
- if you have a history of muscle problems (e.g. myopathy or rhabdomyolysis) during treatment 

with cholesterol-controlling medicines called ‘statins’ (such as simvastatin, atorvastatin, 
pravastatin or rosuvastatin) or fibrates (such as fenofibrate and bezafibrate). 
 

 
Do not take Pravafenix if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before taking Pravafenix. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Pravafenix. 
 
Before you take Pravafenix you should tell your doctor if you have or have had any medical problems. 
- Tell your doctor about all your medical conditions including allergies. 
- Tell your doctor if you drink large amounts of alcohol (if you drink more than the recommended 

daily amount; ask your doctor or pharmacist if you are unsure)  or have ever had liver disease. See 
also below section “Taking Pravafenix with food and drink”. 

- Your doctor should do a blood test before you start taking Pravafenix. This is to check how well 
your liver and your kidneys are working. 

- Your doctor may also want you to have blood tests to check how well your liver is working after 
you start taking Pravafenix. 

 
Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness. 
This is because, on rare occasions, muscle problems can be serious, including muscle breakdown 
resulting in kidney damage, and very rarely deaths have occurred. 
 
Also tell your doctor or pharmacist if you have a muscle weakness that is constant.  
Additional tests and medicines may be needed to diagnose and treat this. 
 
The risk of muscle breakdown is greater in certain patients. Tell your doctor if any of the following 
applies to you: 
- Liver or kidney problems 
- Thyroid problems 
- You are more than 70 years old 
- You have ever had muscle problems during a treatment with cholesterol-lowering medicines such     

as a statin or fibrate 
- You are taking or have taken in the last 7 days a medicine called fusidic acid, (a medicine for 

bacterial infection) orally or by injection. The combination of fusidic acid and Pravafenix can lead 
to serious muscle problems (rhabdomyolysis).  

- You or your close family members have a hereditary muscle disorder 
- You have alcohol problems (regularly drinking large amounts of alcohol) 
 
Check with your doctor or pharmacist before taking Pravafenix if you have severe respiratory failure, 
e.g. you have breathing problems including, persistent non-productive cough, deterioration in general 
health like fatigue (tiredness), weight loss and/or shortness of breath or fever. 



33 
 

If you feel any of these symptoms you should stop taking Pravafenix and inform your doctor. 
 
While you are on this medicine your doctor will monitor you closely if you have diabetes or are at risk 
of developing diabetes. You are likely to be at risk of developing diabetes if you have high levels of 
sugars and fats in your blood, are overweight and have high blood pressure. 
 
Children and adolescents 
Do not take Pravafenix if you are under 18 years old 
 
Other medicines and Pravafenix 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. It is important that you inform your doctor if you are already being treated with any of the 
following: 
- Bile acid resins such as colestyramine/colestipol (a medicine for lowering cholesterol), because it 

affects the way Pravafenix works. 
- Ciclosporin (a medicine often used in organ transplant patients). 
- Medicines to prevent blood clots, such as warfarin, fluindione, phenprocoumon or acenocoumarol 

(anticoagulants)  
- An antibiotic such as erythromycin, clarithromycin to treat infections caused by bacteria. 
- Fusidic acid: If you need to take oral fusidic acid to treat a bacterial infection you will need to 

temporarily stop using this medicine. Your doctor will tell you when it is safe to restart 
Pravafenix. Taking Pravafenix with fusidic acid may rarely lead to muscle weakness, tenderness 
or pain (rhabdomyolysis). See more information regarding rhabdomyolysis in section 4.  

- Glecaprevir/pibrentasvir (used to treat hepatitis C virus infection) because it can increase some 
adverse events including muscle problems.  

 
Pravafenix with food, drink and alcohol 
- Always take Pravafenix with food as Pravafenix is less well absorbed from an empty stomach. 
- You should always keep your alcohol intake to a minimum. If you are concerned about how much 

alcohol you can drink while you are taking this medicine, you should discuss this with your 
doctor.  

If you are not sure about this, please follow your doctor’s advice. 
 
Pregnancy and breast-feeding 
Do not take Pravafenix if you are pregnant or trying to get pregnant or think you may be pregnant. 
If you plan to become pregnant or become pregnant, inform your doctor immediately. The medicine 
must be discontinued because of the potential risk to the foetus. 
 
Do not take Pravafenix if you are breast-feeding. 
 
Driving and using machines 
Pravafenix does not usually affect your ability to drive or use machines. If you experience any 
dizziness, blurred or double vision during treatment, make sure you are fit to drive and use machines 
before attempting to do so. 
 
Pravafenix contains lactose 
Pravafenix contains a sugar called lactose. If you have been told by your doctor that you have 
intolerance to some sugars, contact your doctor before taking this medicine. 
 
 
3. How to take Pravafenix 
 
Always take Pravafenix exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. 
- Before starting taking Pravafenix, you should be on a diet to lower your cholesterol. 
- You should keep to this diet while taking Pravafenix 
 



34 
 

The usual dose is one capsule taken daily during the evening meal. Swallow the capsule with water. It 
is important to take the capsule with food, as it won’t work as well if your stomach is empty. 
 
When your doctor has prescribed Pravafenix along with colestyramine or any other bile acid binding 
resins (medicines for lowering cholesterol), take Pravafenix 1 hour before, or 4 to 6 hours after the 
resin. This is because colestyramine or other bile acid binding resins frequently reduce the absorption 
of medicines when taken too closely together and so may impede the absorption of Pravafenix. If you 
take indigestion remedies (used to neutralise acid in your stomach), take Pravafenix 1 hour after. 
 
If you take more Pravafenix than you should 
Please contact your doctor or pharmacist 
 
If you forget to take Pravafenix 
Do not take a double dose to make up for a forgotten dose, just take your normal amount of Pravafenix 
at the usual time the next day. 
 
If you stop taking Pravafenix 
Do not stop taking Pravafenix without first discussing it with your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
The following two side effects are important and will require immediate action.  
Tell your doctor straight away if you have any unexplained muscular pain or cramps, tenderness, or 
weakness. This is because on very rare occasions (may affect up to 1 in 10,000 people), muscle 
problems can be serious, including muscle breakdown resulting in kidney damage, and very rarely 
deaths have occurred. 
Sudden severe allergic reactions including swelling of the face, lip, tongue or wind pipe which can 
cause great difficulty in breathing. This is a very rare reaction which can be serious if it occurs. You 
should tell your doctor immediately if it happens. 
 
Other Side effects 
 
Common side effects (may affect up to 1 in 10 people) 
• Digestive effects: gastric or intestinal disorders (abdominal pain, nausea, vomiting, diarrhoea and 

flatulence, constipation, dry mouth, upper abdominal pain with bloating (dyspepsia), burping 
(eructation)). 

• Effects on liver: raised serum transaminases. 
 
Uncommon side effects (may affect up to 1 in 100 people) 
• Abnormal heartbeat (palpitations), formation of blood clots in veins (deep vein thrombosis) and 

blockage of the lung arteries by blood clots (pulmonary embolism) 
• Rashes, skin rash, itching, hives or reactions to sunlight or exposure to UV light (photosensitivity 

reactions), scalp/hair abnormality (including hair loss) 
• Effects on nervous system: dizziness (sensation of unsteadiness), headache, sleep disturbances 

(including difficulty sleeping and nightmares), pins and needles sensation (paresthesia). 
• Muscle and joint pain (myalgia, arthralgia), back pain, alterations in some laboratory blood tests 

for muscle function. 
• Problems with sight such as blurred or double vision. 
• Kidney problems (increased or decreased levels of certain enzymes within the body seen in a test) 

bladder problems (painful or frequent urination, having to pass water at night), sexual dysfunction. 
• Tiredness, weakness, influenza-like illness. 



35 
 

• Hypersensitivity. 
• Increased blood cholesterol, increased blood triglycerides, increased LDL, increased gamma-

glutamyl transferase (various liver enzymes), liver pain (upper right abdominal pain with or 
without pain in the back), increased weight. 

• Obesity. 
• Muscle inflammation (myositis), muscular cramps and weakness. 
 
Rare side effects (may affect up to 1 in 1,000 people) 
• Decrease in haemoglobin (oxygen-carrying pigment in blood) and leukocytes (white blood cells). 
 
Very rare side effects (may affect up to 1 in 10,000 people) 
• Inflammation of the liver (hepatitis), symptoms of which may be mild yellowing of the skin and 

whites of the eyes (jaundice), abdominal pain and itching. 
• Muscle breakdown (rhabdomyolysis), some cases of tendon problems, sometimes complicated by 

rupture. 
• A condition characterised by an inflammation of the muscles and the skin (dermatomyositis). 
• Skin rash, possibly with pain in the joints (Erythematous lupus like syndrome). 
• Tingling and numbness (peripheral polyneuropathy). 
 
Side effects of unknown frequency (frequency cannot be estimated from the available data) 
• Muscle weakness that is constant 
• Skin rash (lichenoid eruption) 
 
Possible side effects reported with some statins (same type of cholesterol-lowering medicines as 
pravastatin) 
• Memory loss 
• Depression 
• Breathing problems including persistent cough/or shortness of breath or fever. 
• Diabetes. This is more likely if you have high levels of sugars and fats in your blood, are 

overweight and have high blood pressure. Your doctor will monitor you while you are taking this 
medicine. 

 
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 Pravafenix 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the blister/bottle after 
EXP. The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Pravafenix contains 
 

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


36 
 

• The active substances are fenofibrate and pravastatin. Each hard capsule contains 40 mg 
pravastatin sodium and 160 mg fenofibrate.  

• The other ingredients are:  
- capsule content: lactose monohydrate, cellulose microcrystalline, ascorbyl palmitate, 

povidone, sodium starch glycolate, magnesium stearate, talc, triacetin, sodium hydrogen 
carbonate, lauroyl macrogolglycerides, hydroxypropylcellulose, macrogol 20 000. 

- capsule shell: gelatine, indigo carmine (E132), black iron oxide (E172), titanium dioxide 
(E171), yellow iron oxide (E172). 

 
What Pravafenix looks like and contents of the pack 
 
The capsules are hard gelatine capsule with olive cap and light green body containing a waxy white 
beige mass and a tablet. The capsules are supplied in Polyamide-Aluminium-PVC/aluminium blister 
packs containing 30, 60 or 90 capsules, and in opaque white plastic bottles containing either 14, 30, 60 
or 90 capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder     Manufacturer 
 
Laboratoires SMB s.a.      SMB Technology s.a. 
Rue de la Pastorale, 26-28     Rue du Parc Industriel 39 
B-1080 Brussels       B-6900 Marche en Famenne 
Belgium        Belgium 
 
For any information over this medicine, please contact the local representative of the Marketing 
Authorisation Holder:  
 
België/Belgique/Belgien 
Laboratoires SMB S.A. 
Tél/Tel: + 32.2.411.48.28. 

Lietuva 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

България 
Synapsis Bulgaria Ltd 
Teл.: + 359.2.444.24.94 
 

Luxembourg/Luxemburg 
Laboratoires SMB S.A. 
Tél/Tel: + 32.2.411.48.28. 
 

Česká republika 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Magyarország 
Laboratoires SMB S.A. 
Tel.: + 32.2.411.48.28. 
 

Danmark 
Laboratoires SMB S.A. 
Tlf: + 32.2.411.48.28. 
 

Malta 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Deutschland 
Galephar Pharma GmbH  
Tel: +49 7164 66 26 
 

Nederland 
Galephar B.V. 
Tel: +31 71 562 15 02 
 

Eesti 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Norge 
Laboratoires SMB S.A. 
Tlf: + 32.2.411.48.28. 
 

Ελλάδα 
Meditrina Pharmaceuticals Ltd  
Τηλ: +30 210 67 26 260 
 

Österreich 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

España Polska 



37 
 

Lacer S.A. 
Tel: +34 934 46 53 00 
 

Laboratoires SMB S.A. 
Tel.: + 32.2.411.48.28. 
 

France 
Laboratoires SMB S.A. 
Tél: + 32.2.411.48.28. 
 

Portugal 
Technimede Sociedade  
Técnico-Medicinal S.A. 
Tel: +351 21 041 41 00 
 

Hrvatska  
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

România 
Solartium Group S.r.l. 
Tel: +40 21 211 71 83 
 

Ireland 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Slovenija 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Ísland 
Laboratoires SMB S.A. 
Sími: + 32.2.411.48.28. 
 

Slovenská republika 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Italia 
Abiogen Pharma S.p.A. 
Tel: +39 050 3154 101 
 

Suomi/Finland 
Laboratoires SMB S.A. 
Puh/Tel: + 32.2.411.48.28. 
 

Κύπρος 
Synapsis Trading Limited  
Τηλ: +30 210 67 26 260 
 

Sverige 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

Latvija 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

United Kingdom 
Laboratoires SMB S.A. 
Tel: + 32.2.411.48.28. 
 

 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency website: 
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