Pravastatin and Fenofibrate interacts in the following cases:
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.
The use of pravastatin/fenofibrate 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.
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), pravastatin/fenofibrate is contraindicated during pregnancy.
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.
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. The potential risk for humans is unknown.
No studies in lactating animals have been conducted with pravastatin/fenofibrate. Therefore, taking into account the contra indication of pravastatin during lactation, pravastatin/fenofibrate is contraindicated during breastfeeding.
A small amount of pravastatin is excreted in human breast milk; therefore pravastatin is contraindicated during breastfeeding.
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.
No effect on fertility in reproductive toxicity studies have been observed with both fenofibrate and pravastatin.
There are no data on fertility from the combined use of fenofibrate and pravastatin.
Pravastatin/fenofibrate combination 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.
The most commonly reported adverse reactions (ADRs) during pravastatin/fenofibrate therapy are increased transaminase and gastrointestinal disorders.
In clinical trials, over 1,566 patients received pravastatin/fenofibrate. 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 |
Marked and persistent increases of creatine phosphokinase (CK) have been reported infrequently. In clinical studies, the incidence of important elevations in creatine phosphokinase (CK ≥3 times the ULN, <5 times the ULN) was 1.92% for patients treated with pravastatin/fenofibrate. 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 pravastatin/fenofibrate. Clinically important elevation (CK ≥10 times the ULN without muscular symptoms) was seen in 0.06% of the patients treated with pravastatin/fenofibrate.
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 pravastatin/fenofibrate. Clinically important elevations in serum transaminases (ALT and/or AST ≥5 times the ULN) were seen in 0.38% of the patients treated with pravastatin/fenofibrate.
Additional adverse reactions associated with the use of medicinal products containing pravastatin or fenofibrate observed in clinical trials and postmarketing experience that may potentially occur with pravastatin/fenofibrate 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 | ||
| Myasthenia gravis | Not known | ||
| Eye disorders | Vision disturbance (including blurred vision and diplopia) | Uncommon | |
| Ocular myasthenia | Not known | ||
| 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 secondary to myoglobinuria, myopathy; myositis, polymyositis. Isolated cases of tendon disorders, sometimes complicated by rupture. Erythematous lupus like syndrome. | Very rare | ||
| Rhabdomyolysis | Immune-mediated necrotizing myopathy. | 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:
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.
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