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One 20mg capsule contains 21.06 mg fluvastatin sodium corresponding to 20 mg fluvastatin. Excipient: Each capsule contains 5.00 mg castor oil, hydrogenated
Strength 20 mg: white opaque/orange opaque size 3 capsule, hard
As an adjunct to diet for the reduction of elevated total-C, LDL-C, apo B and TG levels in patients with primary hypercholesterolaemia and mixed dyslipidaemia (Fredrickson types IIa and IIb). Secondary prevention of coronary events after percutaneous coronary intervention in patients with coronary heart disease.
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Prior to treatment, secondary causes of hypercholesterolaemia should be excluded and patients should be placed on a low-cholesterol diet which should be continued during treatment. Fluvastatin capsules are taken in the evening, independently of food. They should be swallowed whole, not chewed, and taken with some water. • Hypercholesterolaemia: The recommended starting doses are from 20 to 40 mg, once daily. For those who do not respond to lower dose, the dose may be increased to 40 mg twice daily according to baseline LDL-C levels and therapeutic goals. • Coronary Heart Disease after percutaneous coronary intervention : The dose is 40 mg twice daily The maximum recommended daily dose is 80 mg. Any dose adjustments of fluvastatin should be made at the earliest after 4 weeks, based on the measurement of serum LDL cholesterol levels. The lipid lowering effects of fluvastatin are enhanced when combined with a bile acid-binding resin (e.g. cholestyramine), fluvastatin should be given at least 4 hours after the resin. Children and adolescents with heterozygous familial hypercholesterolaemia Prior to initiating treatment with fluvastatin in children and adolescents aged 9 years and older with heterozygous familial hypercholesterolaemia, the patient should be placed on a standard cholesterol-lowering diet. Dietary therapy should be continued during treatment. The recommended starting dose is 40mg (1 capsule fluvastatin 40mg) or 80mg (1 capsule fluvastatin 40mg twice daily). The dose of 20mg fluvastatin (1 capsule fluvastatin 20mg) may be adequate in mild cases. Starting doses should be individualised according to baseline LDL-C levels and the recommended goal of therapy to be accomplished. The use of fluvastatin in combination with nicotinic acid, cholestyramine, or fibrates in children and adolescents has not been investigated.
Geriatric population Studies in elderly patients produced no evidence that any dose adjustment of fluvastatin is required in this patient group.
Renal impairment Fluvastatin undergoes hepatic degradation and less than 6% of the administered dose is excreted in the urine. The pharmacokinetics of fluvastatin are unchanged in patients with mild to severe impairment of renal function and no dose adjustment is required in this patient group.
Hepatic impairment Fluvastatin is contraindicated in patients with active liver disease, or unexplained, persistent elevations in serum transaminases |
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- known hypersensitivity to the active substance or to any of the excipients - active liver disease or any unexplained, persistent elevation of serum transaminases, hepatic impairment - pregnancy and lactation - Myopathic disorders |
There is no data on the use of fluvastatin in patients with the rare disease known as homozygous familial hypercholesterolaemia. Consequently, fluvastatin is not currently indicated for this condition.
There has been no experience in the treatment of hyperlipoproteinaemia with severely raised triglyceride values.
Hepatic function
Fluvastatin should be used with caution in patients with a history of hepatic disease or heavy alcohol ingestion.
Since fluvastatin is eliminated primarily via the biliary route and is subject to significant pre-systemic metabolism, the potential exists for drug accumulation in patients with hepatic insufficiency.
It is recommended that liver function tests be performed before the initiation of treatment and periodically thereafter in all patients. Should an increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceed 3 times the upper limit of normal and persist, therapy should be discontinued. In very rare cases, possibly drug-related hepatitis was observed that resolved upon discontinuation of treatment.
Musculoskeletal system
During treatment with HMG-CoA reductase inhibitors, myopathies, including myositis and rhabdomyolysis, have occurred.
In patients with unexplained diffuse myalgias, muscle tenderness or weakness, and/or a marked rise in creatine kinase (CK), the possibility of myopathy, myositis or rhabdomyolysis should be considered. Patients should thus be advised to report immediately any unexplained myalgias, muscle tenderness or weakness, particularly if these symptoms are accompanied by malaise or fever.
Measuring creatine kinase
There are currently no indications that total CK or other plasma muscle enzymes should be regularly monitored in asymptomatic patients on statin therapy. If CK has to be determined, this should not be performed after any energetic activity or if there is any other plausible explanation for a rise in CK, as this would impair correct interpretation of the values.
Prior to treatment
As with all statins, fluvastatin should be used with caution in patients with a tendency to rhabdomyolysis and its complications. Under the following circumstances, CK should be determined prior to treatment with fluvastatin:
- renal insufficiency;
- hypothyroidism;
- a family history of hereditary muscle disease;
- previous history of muscular toxicity with statins or fibrates;
- alcohol abuse;
- elderly patients (> 70 years of age). The need to determine CK should be considered in the light of other risk factors for rhabdomyolysis.
The benefit versus risk ratio should be carefully considered in the above situations. Medical supervision is recommended. If, in these patients, CK values are clearly elevated prior to treatment (more than 5 times the upper limit of normal), repeat tests should be performed after 5 to 7 days to confirm the results. If significantly elevated CK values persist (at more than 5 times the upper limit of normal), treatment should not be started.
During treatment
If muscular complaints, such as pain, weakness or cramps, occur in patients undergoing fluvastatin therapy, CK values should be determined. Treatment should be discontinued if CK values are significantly increased (more than 5 times the upper limit of normal).
If severe muscular complaints occur on a daily basis, therapy withdrawal should be considered, even if CK values are less than 5 times the upper limit of normal.
If muscular symptoms subside and CK values return to normal, resumption of treatment with fluvastatin or another statin can be considered. The lowest dose should be used and treatment should be closely supervised.
The risk of myopathy is known to be increased in patients receiving immunosuppressive drugs (including ciclosporin), fibrates, nicotinic acid or erythromycin together with other HMG-CoA reductase inhibitors. Fluvastatin should be used with caution in patients receiving such concomitant medication.
Pregnancy :
Women of childbearing potential should take adequate contraceptive precautions. If a patient becomes pregnant while taking this class of drug, therapy should be discontinued.
Patients receiving Warfarin or other coumarin derivatives :
It is recommended that prothrombin times are monitored when fluvastatin therapy is initiated, discontinued or the dosage changed.
Excipient:
The presence of Castor oil may cause stomach upset and diarrhoea.
Children and adolescents with heterozygous familial hypercholesterolaemia
In patients aged <18 years, efficacy and safety have not been studied for treatment periods longer than two years. No data are available about the physical, intellectual and sexual maturation for prolonged treatment period. The long-term efficacy of fluvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
Fluvastatin has only been investigated in children of 9 years and older with heterozygous familial hypercholesterolaemia. In the case of pre-pubertal children, as experience is very limited in this group, the potential risks and benefits should be carefully evaluated before the initiation of treatment.
Interstitial lung disease
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.
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Use with caution : Fibrates Bezafibrate - An interaction study between 20mg o.d. fluvastatin and 200mg t.d.s. bezafibrate showed that mean AUC and Cmax values of fluvastatin were increased on average by about 50-60%. No effect was seen on bezafibrate pharmacokinetics. This combination should be used with caution, however, due to the increased risk of developing myopathy and/or rhabdomyolysis when HMG-CoA reductase inhibitors including fluvastatin have been combined with fibrates. Any patient complaining of myalgia should be carefully evaluated. Gemfibrozil - In an interaction study the concomitant administration of fluvastatin and gemfibrozil had no effect on the pharmacokinetics of either drug. The combination should be used with caution, however, due to reports of an increased risk of myopathy and/or rhabdomyolysis when other HMG-CoA reductase inhibitors have been combined with fibrates. Ciprofibrate - Concomitant administration of fluvastatin and ciprofibrate has no effect on the bioavailability of fluvastatin. However, the combination should be used with caution due to reports of an increased risk of myopathy and/or rhabdomyolysis when ciprofibrate is used in combination with other HMG-CoA reductase inhibitors. Nicotinic acid - Concomitant administration of fluvastatin and nicotinic acid has no effect on the bioavailability of fluvastatin. However, the combination should be used with caution due to reports of an increased risk of myopathy and/or rhabdomyolysis when nicotinic acid is used in combination with other HMG-CoA reductase inhibitors. Erythromycin - There are reports of an increased risk of myopathy and/or rhabdomyolysis when other HMG-CoA reductase inhibitors have been combined with erythromycin. The results from an interaction study with a small number of healthy volunteers suggested that erythromycin and fluvastatin were not metabolised by the same isoenzyme, however caution should be exercised when these two drugs are given in combination in view of the interaction seen with other HMG-CoA reductase inhibitors. Ciclosporin - In an interaction study concomitant administration of fluvastatin and ciclosporin resulted in an increase in the bioavailability of fluvastatin by a factor of 1.9. The combination should be used with caution due to the theoretical potential for an increased risk of myopathy and/or rhabdomyolysis. No effect was seen on ciclosporin levels. Warfarin and other coumarin derivatives - Co-administration of fluvastatin with warfarin may commonly cause significant increases in prothrombin time. This has resulted very rarely in serious haemorrhage. Bile-acid sequestering agents - The lipid lowering effects of fluvastatin are enhanced when combined with a bile acid-binding resin (e.g. cholestyramine), fluvastatin should be given at least 4 hours after the resin. Other substrates or inhibitors of CYP2C9 - Co-administration may result in elevated plasma levels of fluvastatin with a consequent potential increased risk of myopathy. Caution should be exercised when other substrates or inhibitors of CYP2C9 are prescribed to patients using fluvastatin. Phenytoin - Co-administration of fluvastatin increased the mean Cmax and the mean AUC of phenytoin. Patients on phenytoin should be carefully monitored when fluvastatin therapy is initiated or when the dose is increased, due to the increased risk of developing phenytoin toxicity or myopathy and/or rhabdomyloysis. Rifampicin - Administration of fluvastatin to subjects pre-treated with rifampicin resulted in a reduction of the bioavailability of fluvastatin. Although at present there is no clinical evidence that fluvastatin efficacy in lowering lipid levels is altered, for patients undertaking long-term rifampicin therapy (e.g. treatment of tuberculosis), appropriate adjustment of fluvastatin dosage may be warranted to ensure a satisfactory reduction in lipid levels. Itraconazole - No interactions have been seen with itraconazole. Nevertheless patients should be closely monitored. Antipyrine - Administration of fluvastatin does not influence the metabolism and excretion of antipyrine. As antipyrine is a model for drugs metabolised by the microsomal hepatic enzyme systems, interactions with other drugs metabolised by these systems are not expected. Propranolol - Concomitant administration of fluvastatin with propranolol has no effect on the bioavailability of fluvastatin. Digoxin - Concomitant administration of fluvastatin with digoxin has no effect on digoxin plasma concentrations. Cimetidine/ranitidine/omeprazole - Concomitant administration of fluvastatin with cimetidine, ranitidine or omeprazole results in an increase in the bioavailability of fluvastatin, which, however, is of no clinical relevance. Oral antidiabetics such as glibenclamide - Co-administration may result in increase in oral antidiabetics levels without incidence in glycemia control. Other concomitant therapy - In clinical studies in which fluvastatin was used concomitantly with angiotensin converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, salicylic acid, H2-blockers and non-steroidal anti-inflammatory drugs (NSAIDs), no clinically significant adverse interactions occurred. Colchicines - There is no information concerning the pharmacokinetic interaction between both Fluvastine and colchicines. However, when both are administered concomitantly, it has been reported incidental cases of miotoxicity, including muscular pain, weakness and rhabdomyolysis. |
Frequency estimate: Very common (
1/10), common (1/100, <1/10), uncommon (1/1000, <1/100), rare (1/10,000, <1/1000); very rare (<1/10,000)
The most commonly reported adverse drug reactions are minor gastrointestinal symptoms, insomnia and headache.
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Blood and lymphatic system disorders |
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Very rare: |
Thrombocytopenia |
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Psychiatric disorders |
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Common: |
Insomnia. |
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Nervous system disorders |
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Common: |
Headache. |
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Very rare: |
Paraesthesia, dysaesthesia, hypoaesthesia and peripheral neuropathy also known to be associated with the underlying hyperlipidemic disorders. |
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Vascular disorders |
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Very rare: |
Vasculitis. |
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Gastrointestinal disorders |
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Common: |
Dyspepsia, abdominal pain, nausea. |
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Very rare : |
Pancreatitis |
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Hepatobiliary disorders |
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Very rare: |
Hepatitis. |
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Skin and subcutaneous tissue disorders |
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Rare: |
Hypersensitivity reactions such as rash, urticaria. |
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Very rare: |
Other skin reactions (e.g. eczema, dermatitis, bullous exanthema), face oedema, angioedema |
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Musculoskeletal and connective tissue disorders |
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Rare: |
Myalgia, muscle weakness, myopathy. |
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Very rare: |
Rhabdomyolysis, myositis, lupus erythematosus-like reactions. |
Biochemical abnormalities:
- Increase of AST and/or ALT levels
- Increase of CK levels
Children and adolescents with heterozygous familial hypercholesterolaemia
The safety profile of fluvastatin in children and adolescents heterozygous familial hypercholesterolaemia assessed in 114 patients aged 9-17 years treated in two open non-comparative clinical trials was similar to the one observed in adults. In both clinical trials no effect was observed on growth and sexual maturation. The ability of the trials to detect any effect of treatment in this area was however low.
The following adverse events have been reported with some statins:
• Sleep disturbances, including insomnia and nightmares
• Memory loss
• Sexual dysfunction
• Depression
• Exceptional cases of interstitial lung disease, especially with long term therapy.
Winthrop Pharmaceuticals UK Ltd
POM – Prescription Only Medicine
Published Friday 20 February 2009
Published Friday 20 February 2009
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Published Wednesday 18 February 2009
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Published Tuesday 10 February 2009
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Published Friday 06 February 2009
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