Chemical formula: C₂₅H₂₄FNO₄ Molecular mass: 421.461 g/mol PubChem compound: 5282452
Pitavastatin interacts in the following cases:
No dosage adjustment is required in mild renal impairment but pitavastatin should be used with caution. Data with 4 mg dose are limited in all grades of impaired renal function. Therefore 4 mg dose should ONLY be used with close monitoring after graded dose titration. In those with severe renal impairment 4 mg dose is not recommended.
The use of fibrates alone is occasionally associated with myopathy. Co-administration of fibrates with statins has been associated with increased myopathy and rhabdomyolysis. Pitavastatin should be administered with caution when used concomitantly with fibrates. In pharmacokinetic studies co-administration of pitavastatin with gemfibrozil resulted in a 1.4-fold increase in pitavastatin AUC; with fenofibrate AUC, increased 1.2-fold.
Co-administration of protease inhibitors with pitavastatin at the same time may result in minor changes in pitavastatin AUC.
Co-administration of a single dose of ciclosporin with pitavastatin at steady state resulted in a 4.6-fold increase in pitavastatin AUC. The effect of steady state ciclosporin on steady state pitavastatin is not known. Pitavastatin is contraindicated in patients being treated with ciclosporin.
Co-administration of erythromycin with pitavastatin resulted in a 2.8-fold increase in pitavastatin AUC. A temporary suspension of pitavastatin is recommended for the duration of treatment with erythromycin or other macrolide antibiotics.
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, pitavastatin treatment should be discontinued throughout the duration of the fusidic acid treatment.
Pitavastatin 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. 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 pitavastatin and fusidic acid should only be considered on a case by case basis and under close medical supervision.
Co-administration of rifampicin with pitavastatin at the same time resulted in a 1.3-fold increase in pitavastatin AUC due to reduced hepatic uptake.
Interaction studies with pitavastatin and niacin have not been conducted. The use of niacin alone has been associated with myopathy and rhabdomyolysis when used as a monotherapy. Thus pitavastatin should be administered with caution when used concomitantly with niacin.
The steady-state pharmacokinetics and pharmacodynamics (INR and PT) of warfarin in healthy volunteers was unaffected by the co-administration of pitavastatin 4 mg daily. However, as for other statins, patients receiving warfarin should have their prothrombin time or INR monitored when pitavastatin is added to their therapy.
Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. 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, statin therapy should be discontinued.
In common with other HMG-CoA reductase inhibitors (statins), there is the potential for myalgia, myopathy and, rarely, rhabdomyolysis to develop. Patients should be asked to report any muscle symptoms. Creatine kinase (CK) levels should be measured in any patient reporting muscle pain, muscle tenderness or weakness especially if accompanied by malaise or fever.
Creatine kinase should not be measured following strenuous exercise or in the presence of any other plausible cause of CK increase which may confound interpretation of the result. When elevated CK concentrations (>5x ULN) are noted, a confirmatory test should be performed within 5 to 7 days.
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.
Pitavastatin is contraindicated during pregnancy. Women of childbearing potential must take appropriate contraceptive precautions during treatment with pitavastatin. Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the fetus, the potential risk for inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. Animal studies show evidence of reproductive toxicity, but no teratogenic potential. If the patient is planning to become pregnant, treatment should be stopped at least one month prior to conception. If a patient becomes pregnant during use of pitavastatin, treatment must be discontinued immediately.
Pitavastatin is contraindicated during breastfeeding. Pitavastatin is excreted in rat milk. It is not known whether it is excreted in human milk.
No current data.
There is no pattern of adverse events that suggests that patients taking pitavastatin will have any impairment of ability to drive and use hazardous machinery, but it should be taken into account that there have been reports of dizziness and somnolence during treatment with pitavastatin.
In controlled clinical trials, at the recommended doses, less than 4% of pitavastatin treated patients were withdrawn due to adverse events. The most commonly reported pitavastatin related adverse reaction in controlled clinical trials was myalgia.
Adverse reactions and frequencies observed in worldwide controlled clinical trials and extension studies, at the recommended doses, are listed below by system organ class. Frequencies are defined as: 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) and not known.
Uncommon: Anaemia
Uncommon: Anorexia
Uncommon: Insomnia
Common: Headache
Uncommon: Dizziness, Dysgeusia, Somnolence
Rare: Visual acuity reduced
Uncommon: Tinnitus
Common: Constipation, Diarrhoea, Dyspepsia, Nausea
Uncommon: Abdominal Pain, Dry Mouth, Vomiting
Rare: Glossodynia, pancreatitis acute
Uncommon: Transaminases (aspartate aminotransferase, alanine aminotransferase) increased
Rare: Jaundice cholestatic
Uncommon: Pruritus, Rash
Rare: Urticaria, Erythema
Common: Myalgia, Arthralgia
Uncommon: Muscle spasms
Frequency unknown: Immune-mediated necrotising myopathy
Uncommon: Pollakiuria
Uncommon: Asthenia, Malaise, Fatigue, Peripheral Oedema
Elevated blood creatinine kinase of >3 times the upper limit of normal (ULN) occurred in 49 out of 2800 (1.8%) patients receiving pitavastatin in the controlled clinical trials. Levels of ≥10 times ULN with concurrent muscle symptoms were rare and only observed in one patient out of 2406 treated with 4mg pitavastatin (0.04%) in the clinical trial programme.
The clinical safety database includes safety data for 142 paediatric patients who received pitavastatin among which 87 patients were in the age range of 6 to 11, and 55 patients were in the age range of 12 to 17. In total, 91 patients received pitavastatin for 1 year with 12 patients receiving pitavastatin for 2.5 years and 2 patients for 3 years. Less than 3% of pitavastatin treated patients were withdrawn due to adverse events. The most commonly reported pitavastatin related adverse reactions in the clinical programme were headache (4.9%), myalgia (2.1%) and abdominal pain (4.9%). Based on the data available, the frequency, type and severity of adverse reactions are expected to be similar in children and adolescents to adults.
A two year prospective post-marketing surveillance study was conducted in nearly 20,000 patients in Japan. The overwhelming majority of the 20,000 patients in the study were treated with 1mg or 2mg pitavastatin and not 4mg. 10.4% of patients reported adverse events for which a causal relationship to pitavastatin could not be ruled out and 7.4% of patients withdrew from therapy due to adverse events. The myalgia rate was 1.08%. The majority of adverse events were mild. Adverse event rates were higher over 2 years in patients with a history of drug allergy (20.4%), or hepatic or renal disease (13.5%).
Adverse reactions and frequencies observed in the prospective post-marketing surveillance study but not in worldwide controlled clinical trials, at the recommended doses are listed below.
Rare: Hepatic function abnormal, Liver disorder
Rare: Myopathy, Rhabdomyolysis
In the post-marketing surveillance study there were two reports of rhabdomyolysis requiring hospitalisation (0.01% of patients).
In addition there are unsolicited post-marketing reports of skeletal muscle effects including myalgia and myopathy in pitavastatin treated patients at all recommended doses. Reports of rhabdomyolysis, with and without acute renal failure, including fatal rhabdomyolysis have also been received. Unsolicited reports of the following events have also been received (the frequency is based on that observed in post-marketing studies):
Uncommon: Hypoaesthesia
Rare: Abdominal discomfort
The following adverse events have been reported with some statins:
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