Fluvastatin 20mg Capsules

One 20mg capsule contains 21.06 mg fluvastatin sodium corresponding to 20 mg fluvastatin.

Excipient:

Each capsule contains 5.00 mg castor oil, hydrogenated

For a full list of excipients, see section 6.1

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. (see section 5.1)

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. (see section 4.5)

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 (see the sections 4.3, 4.4 and 5.2).

- 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 (see section 4.2, 4.4 and 4.8)

- pregnancy and lactation (see sections 4.4 & 4.6)

- Myopathic disorders (see section 4.4)

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. (see section 4.5)

Pregnancy (see sections 4.3 & 4.6):

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 (see section 4.5):

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. (see Section 5.1).

Fluvastatin has only been investigated in children of 9 years and older with heterozygous familial hypercholesterolaemia (for details see section 5.1). 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 (see section 4.8). 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

Use with caution :

Fibrates (see Section 4.4)

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. (see section 4.4)

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. (see section 4.4)

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. (see section 4.4)

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. (see section 4.4)

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. (see section 4.2)

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.

Pregnancy: Since HMG-CoA reductase inhibitors decrease the synthesis of cholesterol and possibly of other biologically active substances derived from cholesterol, they may cause fetal harm when administered to pregnant women, therefore fluvastatin is contraindicated during pregnancy and should be administered to women of childbearing potential only when these patients are unlikely to conceive and have been informed of the potential risk. Women of childbearing potential should take adequate contraceptive precautions. If a patient becomes pregnant while taking this class of drug, therapy should be discontinued. If a patient plans to become pregnant or becomes pregnant, the doctor has to be informed immediately and fluvastatin should be discontinued because of the potential risk to the fetus. (see section 4.3 and 4.4)

Lactation: Fluvastatin is excreted in rat milk. It is not known whether fluvastatin or its metabolite are excreted in human milk. Because many medicinal products are excreted in human milk and because of the potential for serious adverse reactions, women taking fluvastatin should not breast-feed their infants. (see section 4.3).

No studies on the effects on the ability to drive and use machines have been performed.

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.

Biochemical abnormalities:

- Increase of AST and/or ALT levels (see section 4.4)

- Increase of CK levels (see section 4.4)

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 (see section 4.4)

The experience with overdoses of Fluvastatin is very limited. Should an accidental overdosage occur, administration of activated charcoal is recommended. In the case of a very recent oral intake gastric lavage may be considered. Treatment should be symptomatic.

Pharmacotherapeutic group: HMG-CoA reductase inhibitor

ATC-code: C10A A04

Fluvastatin, a fully synthetic cholesterol-lowering agent, is a competitive inhibitor of HMG-CoA reductase, which is responsible for the conversion of HMG-CoA to mevalonate, a precursor of sterols, including cholesterol. Fluvastatin exerts its main effect in the liver. The inhibition of cholesterol biosynthesis reduces the cholesterol in hepatic cells, which stimulates the synthesis of LDL receptors and thereby increases the uptake of LDL particles. The ultimate result of these mechanisms is a reduction of the plasma cholesterol concentration.

A variety of clinical studies has demonstrated that elevated levels of total cholesterol (total-C), LDL-C and apolipoprotein B (a membrane transport complex for LDL-C) promote human atherosclerosis. Similarly, decreased levels of high density lipoprotein cholesterol (HDL-C) and its transport complex, apolipoprotein A, are associated with the development of atherosclerosis. Epidemiologic investigations have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C and inversely with the level of HDL-C. In multicentre clinical trials, those pharmacologic and/or non-pharmacologic interventions that simultaneously lowered LDL-C and increased HDL-C reduced the rate of cardiovascular events (both fatal and non-fatal myocardial infarctions). The overall cholesterol profile is improved with the principal effects being the reduction of total-C and LDL-C. Fluvastatin also produces a moderate reduction in triglycerides and a moderate increase in HDL-C.

In a pooled analysis of all placebo-controlled studies, patients with primary mixed dyslipidaemia (Type IIb) defined as baseline TG levels 200 mg/dL, treatment with Fluvastatin in daily doses ranging from 20 mg to 80 mg (40 mg b.i.d.) demonstrated consistent and significant decreases in total-C, LDL-C, and apo-B, TG, and a modest increase in HDL-C.

In the Lescol Intervention Prevention Study (LIPS), the effect of fluvastatin on major adverse cardiac events (MACE) was assessed in patients with coronary heart disease who had first successful transcathether therapy (TCT). The study included male and female patients (18-80 years old) and with baseline total cholesterol levels ranging from 3.5-7.0 mmol/L.

In this randomised, double-blind, placebo-controlled trial, a total of 1677 patients were recruited (844 in fluvastatin group and 833 in placebo group). The MACE was defined as cardiac death, non fatal MI and re-intervention (including CABG, repeat TCT, or TCT of a new lesion). The dose of fluvastatin used in this study was 80 mg daily over 4 years. Although the overall composite endpoint showed significant reduction in MACE (22%) compared to placebo (p=0.013), the individual components (cardiac death, non fatal MI and re-intervention) failed to reach statistical significance. There was however a trend in favour of fluvastatin. Therapy with fluvastatin reduced the risk of cardiac death and/or myocardial infarction by 31% (p=0.065).

Children and adolescents with heterozygous familial hypercholesterolaemia

The safety and efficacy of fluvastatin in children and adolescent patients aged 9-16 years of age with heterozygous familial hypercholesterolaemia has been evaluated in 2 open label, uncontrolled clinical trials of 2 years' duration. 114 patients (66 boys and 48 girls) were treated with fluvastatin administered as either fluvastatin capsules 20mg – 40mg bid or fluvastatin 80mg extended released tablets using a dose-titration regimen based upon LDL-C response.

The first study enrolled 29 pre-pubertal boys, 9-12 years of age, who had an LDL-C level >90^th percentile for age and one parent with primary hypercholesterolaemia and either a family history of premature ischemic heart disease or tendon xanthomas. The mean baseline LDL-C was 226mg/dL equivalent to 5.8mmol/L (range: 137–354 mg/dL equivalent to 3.6–9.2mmol/L). All patients were started on fluvastatin capsules 20mg daily with dose adjustments every 6 weeks to 40mg daily then 80mg daily (40mg bid) to achieve an LDL-C goal of 96.7 to 123.7mg/dL (2.5mmol/L to 3.2 mmol/L).

The second study enrolled 85 male and female patients, 10 to 16 years of age, who had an LDL-C > 190mg/dL (equivalent to 4.9mmol/L) or LDL-C > 160mg/dL (equivalent to 4.1mmol/L) and one or more risk factors for coronary heart disease, or LCL-C > 160mg/dL (equivalent to 4.1mmol/L) and a proven LDL-receptor defect. The mean baseline LDL-C was 225mg/dL equivalent to 5.8mmol/L (range: 148–343mg/dL equivalent to 3.8–8.9mmol/L). All patients were started on fluvastatin capsules 20mg daily with dose adjustments every 6 weeks to 40mg daily then 80mg daily (fluvastatin 80mg prolonged release tablet) to achieve an LDL-C goal of < 130mg/dL (3.4 mmol/L).

In the first study, fluvastatin 20 to 80mg daily doses decreased plasma levels of total-C and LDL-C by 21% and 27%, respectively. The mean achieved LDL-C was 161 mg/dL equivalent to 4.2mmol/L (range: 74–336mg/dL equivalent 1.9–8.7mmol/L). In the second study, fluvastatin 20 to 80mg daily doses decreased plasma levels of total-C and LDL-C by 22% and 28% respectively. The mean achieved LDL-C was 159 mg/dL equivalent to 4.1mmol/L (range: 90–295mg/dL equivalent to 2.3–7.6mmol/L).

The majority of patients in both studies (83% in the first study and 89% in the second study) were titrated to the maximum daily dose of 80mg. At study endpoint, 26 to 30% of patients in both studies achieved a targeted LDL-C goal of < 130mg/dL (3.4 mmol/L).

Fluvastatin is a racemate of the two erythro enantiomers of which one exerts the harmacological activity. Fluvastatin is absorbed rapidly and completely (98%) following oral administration to fasted volunteers. In a fed state, the drug is absorbed at a reduced rate. Fluvastatin exerts its main effect in the liver, which is also the main organ for its metabolism. The absolute bioavailability assessed from systemic blood concentrations is 24%. The apparent volume of distribution (Vzf) for the drug is 330 L. More than 98% of the circulating drug is bound to plasma proteins, and this binding is unaffected by drug concentration.

The major circulating blood components are fluvastatin and the pharmacologically inactive N-desisopropyl-propionic acid metabolite. The hydroxylated metabolites have pharmacological activity but do not circulate systemically.

The hepatic metabolic pathways of fluvastatin in humans have been characterised. There are multiple, alternative cytochrome P450 (CYP450) pathways involved. However, the major pathway is mediated by CYP2C9 and this pathway is subject to potential interactions with other CYP2C9 substrates or inhibitors. In addition there are several minor pathways (e.g. CYP3A4).

Several detailed in vitro studies have addressed the inhibitory potential of fluvastatin on common CYP isoenzymes. Fluvastatin inhibited only the metabolism of compounds that are metabolized by CYP2C9.

Following administration of 3H-fluvastatin to healthy volunteers, excretion of radioactivity is about 6% in the urine and 93% in the faeces, and fluvastatin accounts for less than 2% of the total radioactivity excreted. The plasma clearance (CL/f)for fluvastatin in man is calculated to be 1.8 ± 0.8 L/min. Steady-state plasma concentrations show no evidence of fluvastatin accumulation following administration of 40 mg daily. Following oral administration of 40 mg of fluvastatin, the terminal disposition half-life for fluvastatin is 2.3 ± 0.9 hours.

Food: Although AUC and Cmax were lowered and tmax prolonged when fluvastatin was taken with food, there was no apparent difference in the lipid-lowering effect whether fluvastatin was taken with food or not.

Plasma concentrations of fluvastatin do not vary as a function of either age or gender in the general population.

Children and adolescents with heterozygous familial hypercholesterolaemia

No pharmacokinetic data in children are available.

Repeat toxicity studies with fluvastatin identified a variety of changes that are common to HMG-CoA reductase inhibitors, viz. hyperplasia and hyperkeratosis of the rodent non-glandular stomach, cataracts in dogs, myopathy in rodents, mild liver changes in most laboratory animals, with gall bladder changes in the dog, monkey and hamster, thyroid weight increases in the rat and testicular degeneration in the hamster. Fluvastatin is devoid of the CNS vascular and degenerative changes recorded in dogs with other members of this class of compounds.

Carcinogenicity studies in rats and mice revealed a low incidence of forestomach squamous papillomas in mice and rats and one carcinoma in rats at the highest dose (18 mg/kg per day escalated to 24 mg/kg per day after 1 year). The forestomach neoplasms reflect chronic hyperplasia caused by direct contact exposure to fluvastatin rather than a genotoxic effect of the drug. In addition, an increase incidence of thyroid follicular cell neoplasms in male rats given the highest dose of fluvastatin was recorded. This is consistent with species-specific findings with other HMGCoA reductase inhibitors. In contrast to other HMG-CoA reductase inhibitors, no treatment-related increases in the incidence of hepatic adenomas or carcinomas were observed.

In vitro and in vivo mutagenicity studies revealed no evidence of mutagenicity.

Reproductive toxicity studies indicated that fluvastatin had no adverse effects on fertility or reproductive performance in males or females, nor was it embryotoxic or teratogenic. Late gestational effects at high doses resulted in maternal mortality and fetal and neonatal lethality attributable to exaggerated pharmacological effects of fluvastatin during pregnancy.

Capsule content : Mannitol, Cellulose microcrystalline, Calcium lactate pentahydrate, Carmellose calcium, Calcium phosphate, Calcium hydrogen phosphate dihydrate, Castor oil hydrogenated, Magnesium stearate, silica colloidal anhydrous

Capsule shell :

Body Composition: Titanium dioxide E 171, Gelatine

Cap Composition : Red iron oxide E 172, Yellow iron oxide E 172, Titanium dioxide E 171, Gelatine

Not applicable.

18 months

Do not store above 25°C.

Blister consisting of combined aluminium forming (OPA/Alu/PVC) and aluminium lidding foil.

The 20mg capsules are contained in packs of 10, 14, 28, 30, 50, 100

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.

Winthrop Pharmaceuticals UK Ltd

One Onslow Street

Guildford Surrey GU1 4YS

United Kingdom

PL 17780/0290

01/05/2008

01/12/2009