Pitavastatin

Substance from the group of statins.

Mode of action: competitive, reversible inhibition of HMG-CoA reductase, the rate-determining key enzyme in cholesterol synthesis; reduction of endogenous cholesterol synthesis and lowering of total cholesterol and LDL cholesterol levels.

Relatively new substance, first approved in 2011.

HWZ: 5.7-8.9 hours, best efficacy in the evening, corresponding to the circadian maximum of cholesterol synthesis at night or early in the morning.

Statin with broad spectrum of activity (dose-dependent) max. possible LDL reduction dose-dependent: 33 to 54 %

Adapted indication for liver dysfunction and renal function impairment according to severity! Generally high dosage, i.e. avoid 4 mg!

Rapid absorption, high bioavailability at approx. 60%,

Plasma protein binding approx. 99%,

Only minimal metabolization via Cyt P 450 (CYP2C9 and CYP2C8).

Is actively transported by various hepatic transporters, including OATP1B1 and OATP1B3, into the hepatocytes (the site of action and the site of metabolism) (in particular, WW is also possible through this).

Genetic polymorphism: AUC in plasma variable with about factor 4 between highest and lowest value; SLCO1B1 (the gene coding for OATP1B1) probably main cause; causative for interindividual variability in potency and risk for severe NW.

Not a substrate of p-glycoprotein.

Elimination unchanged via the bile into the intestine, long duration of action due to strong enterohepatic circulation.

Only very low elimination unchanged via the kidneys (approx. 5%).

For further details see technical info!

Indication according to guidelines on the basis of and in combination with lifestyle measures (dietary changes, exercise, weight reduction, smoking cessation if necessary) (Mach F et al 2020).

Hypercholesterolemia, dyslipidemia.

Primary prevention: for increased risk of cardiovascular disease (≥10% SCORE2/SCORE2-OP).

Secondary prevention: with pre-existing cardiovascular disease or a history of a serious vascular event.

Heterozygous familial hypercholesterolemia (FH).

From 6 years of age.

In children, observe age-dependent maximum doses, treatment and monitoring only by a specialist (guideline).

Cholesterol and other intermediate products of cholesterol biosynthesis are essential in embryonic and fetal development and necessary for the synthesis of steroids and cell membranes!

Statins are therefore contraindicated during pregnancy and breastfeeding.

The potential risk of damage justifies a break in therapy.

Women and young girls of childbearing age need effective contraception (note interactions!)

For further information see specialist information!

In case of unexpected pregnancy during treatment, see Embryotox Charité

Frequent:

• myopathic complaints (differentiation of non-specific complaints from SAMS and nocebo effect), headache, dizziness, Ùnausea, gastrointestinal complaints;

More frequently also:

• Slight, reversible increase in liver enzymes, note: signs of cholestasis or liver damage (jaundice, brown coloration of urine);
• Increased risk of diabetes mellitus or deterioration of blood glucose control (risk especially in obesity, metabolic syndrome, prediabetes);

Very rare:

• Myositis, severe myopathy with rhabdomyolysis and renal failure;
• Hepatotoxic liver damage;

Very rare or isolated cases:

• Interstitial lung disease with long-term use.
• Myasthenia gravis, ocular myasthenia or worsening.
• During or after treatment with some statins, immune-mediated necrotizing myopathy (IMNM) has been reported; clinical characteristics of IMNM are persistent proximal muscle weakness and elevated serum creatine kinase levels that persist despite discontinuation of treatment with statins.
• Only indicated with caution in the case of a pre-existing predisposition or factors favoring rhabdomyolysis;
• In particular in the case of: impaired renal function, hypothyroidism, hereditary muscle diseases in the patient's own or family history (note possible contraindication!), muscular-toxic symptoms under fibrates or other statins in the patient's history (strict individual indication, if necessary, alternatives!), liver diseases in the patient's own or family history (note possible contraindication!). alternatives!), history of liver disease or alcohol abuse, elderly patients (over 70 years) with other risk factors that predispose to rhabdomyolysis (generally strict individual risk-benefit assessment, do not start treatment if CK≥5 times the upper normal value!) Determine the CK values before starting treatment (initial value as reference)!

Enzyme systems/carriers and selection of substances with potential for interaction (inhibition), enhancement of effect and risk of serious adverse effects with concomitant treatment with pitavastatin

P-gp (ABCB1)

Amiodarone, azithromycin, captopril, carvedilol, quinidine, cimetidine, clarithromycin, colchicine, conivaptan, ciclosporin, diltiazem, dronedarone (potent), erythromycin, itraconazole, nicardipine, protease inhibitors (HIV), ranolazine, ticagrelor, verapamil

OATP1B1

Carbamazepine, clarithromycin, ciclosporin, erythromycin, gemfibrozil, protease inhibitors (HIV), roxithromycin, sacubitril

only low potential for WW due to Cyt P 450 but pitavastatin is actively transported into hepatocytes by several hepatic transporters (also by organic anion transporting polypeptide, OATP), therefore:

not cyclosporine (contraindicated!),

not together with erythromycin or macrolide antibiotics (pause for the duration of treatment)

Fusidic acid (pause for the duration of treatment plus 7 days!),

no gemfibrozil and other fibrates, no niacin (risk of severe myopathy/rhabdomyolysis),

Rifampicin,

For further information and for substances that can be used with dose restrictions, see specialist information.

This information is only a selection! Further interactions must be clarified individually in each case! (for further information, see specialist information or databases on drug interactions).

It should also be noted that statins can alter the effect of concomitant medication and this can also result in additional incompatibilities!

Interaction studies have only been carried out in adults.

Especially in special patient groups with polypharmacotherapy, the risk of side effects is increased!

Pitavastatin (^Livazo®, generic) 1 mg, 2 mg, 4 mg; approved from 6 years of age.

1. Mach F et al (2020). 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) European Heart Journal 41:111-188.