Pravafenix

Pravafenix is a medicine that contains the active substances pravastatin and fenofibrate. It is available as green and olive capsules containing 40 mg pravastatin and 160 mg fenofibrate.

Pravafenix is used in adults at high risk of heart disease whose ‘low-density-lipoprotein’ (LDL or ‘bad’) cholesterol is already being controlled with pravastatin alone but who still need to improve their cholesterol levels and to reduce their levels of triglycerides (a type of fat).

The medicine can only be obtained with a prescription.

Because pravastatin and fenofibrate have been used in medicines for a number of years, the company presented information from the scientific literature in addition to results from its own studies.

The company carried out one main study, in which Pravafenix was compared with pravastatin alone in 248 patients at high risk of heart disease who had abnormal levels of cholesterol and triglyceride fats. The main measure of effectiveness was the reduction in the level of cholesterol after 12 weeks (excluding HDL or ‘good’ cholesterol).

In the main study Pravafenix was shown to be more effective than pravastatin alone in reducing non-HDL-cholesterol levels. Non-HDL-cholesterol levels were reduced on average by around 14% in patients taking Pravafenix compared with 6% in patients taking pravastatin alone.

The most common side effects with Pravafenix (seen in between 1 and 10 patients in 100) are abdominal distension (bloating), abdominal pain (stomach ache), constipation, diarrhoea, dry mouth, dyspepsia (heartburn), eructation (belching), flatulence (gas), nausea (feeling sick), abdominal discomfort, vomiting and raised blood levels of liver enzymes. For the full list of all side effects reported with Pravafenix, see the package leaflet.

Pravafenix should not be used in people who may be hypersensitive (allergic) to the active substances or any of the other ingredients. Pravafenix must not be used in patients aged below 18 years or in patients with severe liver problems, moderate to severe kidney problems, photo-allergy or phototoxic reactions (allergic reaction or skin damage due to light exposure) during treatment with fibrates or ketoprofen. It must also not be used in patients with gall-bladder disease, chronic or acute pancreatitis (inflammation of the pancreas) or a history of myopathy (muscle disorders) or rhabdomyolysis (breakdown of muscle fibres) following treatment with a statin or a fibrate. It must not be given to women who are pregnant or breastfeeding.

The CHMP looked at newly published data on the benefits of the combination of statins and fenofibrate. The Committee also noted that the benefits of Pravafenix were mainly in patients who had high levels of triglyceride fats and low levels of HDL cholesterol. The Committee therefore decided that Pravafenix’s benefits are greater than its risks in this group of patients and recommended that it be given marketing authorisation.

Pravafenix received a marketing authorisation valid throughout EU on 14 April 2011.

Pravafenix can only be obtained with a prescription. It is available as capsules to be taken by mouth once a day with food, during the evening meal. Before starting treatment with Pravafenix, the doctor should first investigate all possible causes of the patient’s abnormal cholesterol and triglyceride blood levels and recommend a suitable diet.

The patient’s blood should be monitored regularly to see how the medicine is working. The doctor should stop treatment if an adequate response does not occur within three months.

The active substances in Pravafenix, pravastatin and fenofibrate, work in different ways and their actions have a complementary effect.

Pravastatin belongs to a group of medicines called statins. It reduces total blood cholesterol by blocking the action of the HMG-CoA reductase, an enzyme (protein) in the liver involved in the production of cholesterol. As the liver needs cholesterol to produce bile, the reduced blood cholesterol level causes the liver cells to produce receptors that draw LDL cholesterol from the blood, reducing its level even further.

Fenofibrate attaches to the peroxisome proliferator‑activated receptor alpha (PPAR alpha), which is involved in breaking down fat from the diet, especially triglycerides. When the receptors are activated, the breakdown of fats is accelerated, and this helps clear the blood of cholesterol and triglycerides.

Because pravastatin and fenofibrate have been used in clinical practice for a long time, the company presented information from the scientific literature. Additionally, a main study showed that Pravafenix is more effective than pravastatin alone in reducing blood levels of non-HDL cholesterol.

The main study involved 248 patients at high risk of heart disease who had abnormal levels of cholesterol and triglycerides in the blood. Patients were either treated with Pravafenix or pravastatin alone. After 12 weeks of treatment, non-HDL cholesterol was reduced by an average of around 14% in patients taking Pravafenix, compared with an average of around 6% in patients taking pravastatin alone.

An additional study confirmed the effectiveness of Pravafenix compared with other statin medicines given alone in patients treated by different doctors such as family doctors, cardiologists or endocrinologists.

For the complete list of side effects and restrictions with Pravafenix, see the package leaflet.

The most common side effects with Pravafenix (which may affect up to 1 in 10 people) include abdominal distension (bloating), abdominal (belly) pain, constipation, diarrhoea, dry mouth, dyspepsia (heartburn), eructation (belching), flatulence (gas), nausea (feeling sick), abdominal discomfort, vomiting and raised blood levels of liver enzymes.

Pravafenix must not be used in patients aged less than 18 years or in patients with severe liver problems, moderate to severe kidney problems, photo allergy or phototoxic reactions (allergic reaction or skin damage due to light exposure) during treatment with fibrates or ketoprofen medicines. It must also not be used in patients with gall bladder disease, chronic or acute pancreatitis (inflammation of the pancreas) or a history of myopathy (muscle disorders) or rhabdomyolysis (breakdown of muscle fibres) following treatment with a statin or fibrate medicine. It must not be taken by women who are pregnant or breastfeeding.

Data from the scientific literature and from two studies show that Pravafenix, which combines a statin and fenofibrate, is more effective than a statin alone to reduce LDL cholesterol in patients who have high levels of triglycerides and low levels of HDL cholesterol. Regarding safety, side effects with Pravafenix were considered acceptable for the patients in which it is used.

The European Medicines Agency therefore decided that Pravafenix’s benefits are greater than its risks and it can be authorised for use in the EU.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pravafenix have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pravafenix are continuously monitored. Suspected side effects reported with Pravafenix are carefully evaluated and any necessary action taken to protect patients.