Chemical formula: C₂₄H₃₆O₅ Molecular mass: 404.54 g/mol PubChem compound: 53232
Lovastatin interacts in the following cases:
Grapefruit juice contains one or more ingredients that inhibit cytochrome P450 3A4 and may therefore increase the plasma concentrations of medicinal products metabolized via cytochrome P450 3A4. The effect of typical consumption (one 250 ml glass daily) is minimal (34% increase in active plasma HMG-CoA reductase inhibitory activity as measured by the area under the concentration-time curve) and of no clinical relevance. However, very high quantities of grapefruit juice (more than a litre a day) significantly increase the inhibitory activity of HMG-CoA reductase during lovastatin therapy and such quantities should therefore be avoided.
In patients with severe renal failure (creatinine clearance <30 ml/min) dosages over 20 mg/day should be carefully considered, and, if necessary, should be commenced with caution
When lovastatin and coumarin derivatives are used concurrently, prothrombin time may be prolonged in some patients. In patients receiving anticoagulant therapy, prothrombin time should be determined before starting lovastatin therapy and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, it can be determined at the intervals usually recommended for patients receiving coumarin therapy. If the dose of lovastatin is changed, the same procedures should be repeated. Lovastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not receiving anticoagulant therapy.
The risk of myopathy is also increased by the following lipid-lowering drugs that are not potent inhibitors of CYP3A4, but which can cause myopathy when given alone: gemfibrozil, other fibrates, niacin (nicotinic acid), at lipid-lowering doses (≥1 g/day).
Co-administration of lovastatin and gemfibrozil led to a considerable increase in the concentration of the active metabolite in plasma in healthy volunteers compared with coadministration of lovastatin and placebo.
Fertility was impaired in dogs with dosages from 20 mg/kg/day, but a fertility study in rats proved negative.
The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol particularly with higher doses of lovastatin.
The risk of myopathy may be increased when fusidic acid is used concomitantly with a closely related member of the HMG-CoA reductase inhibitor class.
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.
Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above 10X the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.
Lovastatin is contraindicated during pregnancy.
Safety in pregnant women has not been established. No controlled clinical trials with lovastatin have been carried out in pregnant women. There have been rare reports of congenital abnormalities following intrauterine exposure to HMG-CoA reductase inhibitors. In an analysis of approximately 200 prospectively followed pregnancies in women who were treated with lovastatin or another closely related HMG-CoA reductase inhibitor, the incidence of congenital abnormalities was compared with the incidence in the population in general. The number of pregnancies was statistically adequate to exclude a 2.5-fold or greater increase in congenital abnormalities in relation to the general incidence.
Even though there are no signs of a difference in the incidence of congenital abnormalities in children born to patients who take lovastatin or another closely related HMG-CoA reductase inhibitor and the incidence in the population in general, treatment of the mother with lovastatin can reduce the fetal level of mevalonate, which is a precursor stage in cholesterol biosynthesis. Arteriosclerosis is a chronic process, and withdrawal of lipid-lowering agents during pregnancy probably has no noteworthy influence on the result of long-term treatment of primary hypercholesterolaemia. Lovastatin should therefore not be used in pregnant women, women who are trying to become pregnant, or if pregnancy is suspected. Treatment with lovastatin should be suspended during pregnancy or until it is established that the women is not pregnant.
It is not known whether lovastatin or its metabolites are excreted into breast milk. As many drugs are excreted into breast milk, and as there is a potential risk of serious undesirable effects, women taking lovastatin should not breast-feed.
Lovastatin has no or negligible influence on the ability to drive and use machines. However, when driving vehicles or operating machines, it should be taken into account that dizziness has been reported rarely in post-marketing experiences.
Lovastatin is generally well tolerated; the adverse reactions of lovastatin have for the most part been mild and transient.
The frequency of adverse reactions can be ranged as follows: 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), not known (cannot be estimated from the available data).
The following list shows the adverse effects based on data derived from clinical studies and from post-marketing experience.
Rare: Hypersensitivity syndrome associated with one or more of the following symptoms: anaphylaxis, angioedema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, leucopenia, eosinophilia, haemolytic anaemia, positive antinuclear antibodies (ANA), increased sedimentation rate, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, flushes, chills, dyspnoea and malaise.
Common: Digestive disorders.
Rare: Anorexia.
Uncommon: Insomnia, sleeping difficulties.
Rare: Psychological disturbances including restlessness/anxiety.
Not known: Depression.
Common: Vertigo, cephalagia.
Uncommon: Dysgeusia.
Rare: Peripheral neuropathy, in particular if used for a long period of term, paraesthesia.
Memory impairment.
Common: Blurred vision
Common: Flatulence, diarrhoea, constipation, nausea, dyspepsia, abdominal pains.
Rare: Vomiting.
Rare: Hepatitis, cholestatic jaundice.
Common: Rash.
Uncommon: Pruritus, xerostomia.
Rare: Hair loss, toxic epidermal necrolysis and erythema multiforme including Stevens-Johnson syndrome
Common: Muscle cramps and myalgia.
Rare: Myopathia and rhabdomyolysis, erectile dysfunction
Uncommon: Tiredness
Rare: Marked and persistent increases in serum transaminase concentrations. Other irregularities in liver function tests, including elevated alkaline phosphatase and bilirubin have been reported. Increases in the serum concentration of CK (which may be attributed to the non-cardiac fraction of CK) have been seen. These have usually been slight and transient; marked increases have only occurred in rare cases.
In the 48-week expanded clinical evaluation of lovastatin (EXCEL study) comparing lovastatin to placebo, the adverse experiences reported were similar to those of the initial studies, and the incidence on drug and placebo was not statistically different.
The following additional adverse events have been reported with some statins:
In a 48-week controlled study in adolescent boys with heterozygous familial hypercholesterolemia (n=132) and a 24-week controlled study in girls who were at least 1 year post-menarche with heterozygous familial hypercholesterolemia (n=54), the safety and tolerability profile of the groups treated with lovastatin (10 to 40 mg daily) was generally similar to that of the groups treated with placebo.
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