Choleste

Choleste Uses, Dosage, Side Effects, Food Interaction and all others data.

Choleste is a preparation of Choleste which acts as a Cholesterol lowering agent. The main mechanism of reduction of low density lipoprotein (LDL) cholesterol is that following inhibition of HMG-CoA reductase activity, the LDL receptor density on the liver cells is increased and this leads to an increased removal of LDL cholesterol from the plasma and increased catabolism of LDL cholesterol. In addition, there is a reduction in the very low- density lipoprotein (VLDL) cholesterol and reduced formation of LDL from VLDL. Choleste is extensively metabolised in the liver; which is also the main site of action of the drug.

Choleste is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.

Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with 11,12

Skeletal Muscle Effects

Trade Name Choleste
Availability Prescription only
Generic Simvastatin
Simvastatin Other Names Simvastatin, Simvastatina, Simvastatine, Simvastatinum
Related Drugs Nexletol, Nexlizet, Zetia, Praluent, Repatha, atorvastatin, Xarelto, rosuvastatin, Lipitor, Brilinta
Type
Formula C25H38O5
Weight Average: 418.5662
Monoisotopic: 418.271924326
Protein binding

Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.

Groups Approved
Therapeutic Class Other Anti-anginal & Anti-ischaemic drugs, Statins
Manufacturer
Available Country South Africa
Last Updated: September 19, 2023 at 7:00 am
Choleste
Choleste

Uses

Primary hypercholesterolemia (type IIa and IIb) in patients who have not responded adequately to diet and other appropriate measures. Coronary heart disease and elevated plasma cholesterol level.

Choleste is also used to associated treatment for these conditions: Cardiovascular Events, Diabetes Mellitus, Heterozygous Familial Hypercholesterolemia, High Cholesterol, Homozygous Familial Hypercholesterolemia, Mixed Hyperlipidemia, History of coronary heart disease cardiovascular event, History of stroke or other cerebrovascular disease cardiovascular event

How Choleste works

Choleste is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Choleste acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Choleste also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL.

At therapeutic doses, the HMG-CoA enzyme is not completely blocked by simvastatin activity, thereby allowing biologically necessary amounts of mevalonate to remain available. As mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with simvastatin would also not be expected to cause any accumulation of potentially toxic sterols. In addition, HMG-CoA is metabolized readily back to acetyl-CoA, which participates in many biosynthetic processes in the body.

In vitro and in vivo animal studies also demonstrate that simvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.

Statins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.

Dosage

Choleste dosage

The patient should be placed on a standard cholesterol lowering diet before receiving Choleste and should continue on this during treatment with Choleste. The usual starting dose is 10 mg/day given as a single dose in the evening. Adjustment of dosage, if required, should be made at intervals of not less than four weeks, to a maximum of 40 mg daily given as a single dose in the evening. If LDL-cholesterol levels fall below 2 mmol/L or total plasma cholesterol levels fall below 3.5 mmol/L consideration should be given to reducing the dose of Choleste. In hypercholesterolemia, the recommended starting dose is 5-10 mg once a day in the evening and the recommended dosing range is 5-40 mg per day as a single dose in the evening. In patients with coronary heart disease and hypercholesterolemia, the starting dose should be 20 mg once a day in the evening. Because Choleste does not undergo significant renal excretion, modification of dosage should not be necessary in patients with renal insufficiency. Safety and effectiveness in children and adolescents have not been established.

Side Effects

Choleste is generally well tolerated. Headache, fatigue, insomnia, gastrointestinal effects like nausea, constipation or diarrhoea, flatulence, dyspepsia, abdominal cramps and muscular effects like myalgia, myositis and myopathy have been reported. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been associated with Choleste therapy. Hepatitis, pancreatitis, rash, Angio-oedema have also been reported. No potentially life threatening effects have been reported.

Precaution

  • If there is a history of liver disease
  • Who take high alcohol
  • Liver function test should be done before and during treatment
  • If serum transaminase rises three times the upper limit of normal, treatment should be discontinued
  • Avoid pregnancy during and for one month after treatment

Interaction

Digoxin: Concomitant administration of Choleste and Digoxin in normal volunteers resulted in a slight elevation (less than 0.3 µgm/ml) in drug concentrations in plasma compared to concomitant administration of placebo and Digoxin.

Coumarin derivatives: Slightly enhance the anticoagulant effect of Warfarin (mean changes in p rothrombin time less than two seconds) in normal volunteers maintained in a state of low therapeutic anticoagulation.

Others: In clinical studies, Choleste was used concomitantly with ACE inhibitors, beta-blockers, calcium channel blockers, diuretics and NSAIDs without evidence of clinically significant adverse interactions.

Food Interaction

  • Avoid grapefruit products. Co-administration with grapefruit products may increase the risk for adverse effects such as myalgia.

[Major] GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

When a single 60 mg dose of simvastatin was coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold.

Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold, respectively.

The interaction has also been reported with lovastatin, which has a similar metabolic profile to simvastatin.

Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity.

Myopathy manifested as muscle pain and

Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

Coadministration with green tea may increase the plasma concentrations of simvastatin.

The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1B1- and

The interaction was suspected in a 61-year-old man who experienced muscle intolerance during treatment with simvastatin while drinking an average of 3 cups of green tea daily.

He also experienced similar muscle intolerance (leg cramps without creatine phosphokinase elevation) during treatments with atorvastatin and rosuvastatin while drinking green tea.

Pharmacokinetic studies performed during his usual green tea intake demonstrated an approximately two-fold higher exposure to simvastatin lactone (the administered form of simvastatin) than that observed after stopping green tea intake for a month.

He was also able to tolerate simvastatin after discontinuing green tea consumption.

The authors of the report subsequently conducted two independent studies to assess the effect of different green tea preparations on simvastatin pharmacokinetics.

One study was conducted in 12 Italian subjects and the other in 12 Japanese subjects.

In the Italian study, administration of a single 20 mg dose of simvastatin following pretreatment with 200 mL of a hot green tea standardized infusion 3 times daily for 14 days (estimated daily intake of 335 mg total catechins and 173 mg epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea) was found to have no significant effect on mean peak plasma concentration (Cmax) or systemic exposure (AUC) of simvastatin lactone and simvastatin acid relative to administration with water.

However, green tea increased simvastatin lactone AUC (0-6h) by about two-fold in 3 of the study subjects.

In the Japanese study, administration of a single 10 mg dose of simvastatin following pretreatment with 350 mL of a commercial green tea beverage twice daily for 14 days (estimated daily intake of 638 mg total catechins and 322 mg EGCG) did not affect mean simvastatin lactone Cmax or AUC to a statistically significant extent compared to administration with water, but increased mean simvastatin acid Cmax and AUC by 42% and 22%, respectively.

Similar to the first study, green tea increased simvastatin lactone AUC (0-6h) by two- to three-fold in 4 of the study subjects.

Although not studied, the interaction may also occur with lovastatin due to its similar metabolic profile to simvastatin.

MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice.

Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals.

All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and

Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided.

Caution may be advisable when coadministered with green tea or green tea extracts.

Dosing reduction of the statin and

Choleste Alcohol interaction

[Moderate]

Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury.

Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins.

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.

Active liver disease or unexplained transaminase elevations are contraindications to statin use.



Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

Volume of Distribution

Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.

Elimination Route

Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours post-dose. While the recommended therapeutic dose range is 10 to 40 mg/day, there was no substantial deviation from linearity of AUC with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before a test meal.

In a pharmacokinetic study of 17 healthy Chinese volunteers, the major PK parameters were as follows: Tmax 1.44 hours, Cmax 9.83 ug/L, t1/2 4.85 hours, and AUC 40.32ug·h/L.

Choleste undergoes extensive first-pass extraction in the liver, the target organ for the inhibition of HMG-CoA reductase and the primary site of action. This tissue selectivity (and consequent low systemic exposure) of orally administered simvastatin has been shown to be far greater than that observed when the drug is administered as the enzymatically active form, i.e. as the open hydroxyacid.

In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. However, because simvastatin undergoes extensive first-pass metabolism, the bioavailability of the drug in the systemic system is low. In a single-dose study in nine healthy subjects, it was estimated that less than 5% of an oral dose of simvastatin reached the general circulation in the form of active inhibitors.

Genetic differences in the OATP1B1 (Organic-Anion-Transporting Polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact simvastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) showed that simvastatin plasma concentrations were increased on average 3.2-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals. The 521CC genotype is also associated with a marked increase in the risk of developing myopathy, likely secondary to increased systemic exposure. Other statin drugs impacted by this polymorphism include rosuvastatin, pitavastatin, atorvastatin, lovastatin, and pravastatin.

For patients known to have the above-mentioned c.521CC OATP1B1 genotype, a maximum daily dose of 20mg of simvastatin is recommended to avoid adverse effects from the increased exposure to the drug, such as muscle pain and risk of rhabdomyolysis.

Evidence has also been obtained with other statins such as rosuvastatin that concurrent use of statins and inhibitors of Breast Cancer Resistance Protein (BCRP) such as elbasvir and grazoprevir increased the plasma concentration of these statins. Further evidence is needed, however a dose adjustment of simvastatin may be necessary. Other statin drugs impacted by this polymorphism include fluvastatin and atorvastatin.

Half Life

4.85 hours

Elimination Route

Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.

Pregnancy & Breastfeeding use

Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Contraindication

Choleste should not be used in-

  • Active liver disease
  • Pregnant and breast feeding mother
  • Women of child bearing age unless they have been adequately protected by contraception
  • Hypersensitivity to any component of the preparation
  • Patients with the homozygous familial hypercholesterolemia who have a complete absence of LDL receptors

Acute Overdose

There are no data available on overdose. No antidote is available. General measures should be adopted and liver function should be monitored.

Storage Condition

Store in a cool, dry place, Away from light keep out of reach of children.

Innovators Monograph

You find simplified version here Choleste

Choleste contains Simvastatin see full prescribing information from innovator Choleste Monograph, Choleste MSDS, Choleste FDA label

FAQ

What is Choleste used for?

Choleste is used to lower cholesterol if you've been diagnosed with high blood cholesterol. It's also taken to prevent heart disease, including heart attacks and strokes.

How safe is Choleste?

Choleste seems to be a very safe medicine. It's unusual to have any side effects. Keep taking Choleste even if you feel well, as you will still be getting the benefits. Most people with high cholesterol don't have any symptoms.

How does Choleste work?

Choleste works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

What are the common side effects of Choleste?

Common side effects of Choleste include:

  • CPK elevation (greater than 3x ULN)
  • Constipation
  • Upper respiratory infection
  • Gas (flatulence)
  • Transaminases increased (greater than 3x ULN)
  • Headache
  • Muscle pain, muscle damage, or muscle weakness
  • Eczema
  • Spinning sensation (vertigo)
  • Abdominal pain

Is Choleste safe during pregnancy?

Choleste are not recommended for pregnant women.

Is Choleste safe during breastfeeding?

Choleste should not be used during breastfeeding.

Can I drink alcohol with Choleste?

Yes, you can drink alcohol while taking Choleste. However, drinking a lot of alcohol may increase the chances of you getting muscle and liver side effects.

Can I drive after talking Choleste?

Yes, you can drive or cycle while taking Choleste.

What should I avoid while taking Choleste?

Drinking large amounts of grapefruit juice (more than 1 quart each day) while taking this medicine may increase your risk of muscle injury and could result in kidney problems.

When is the best time to take Choleste?

Choleste is probably best taken at night because concentrations of total cholesterol and of low density lipoprotein are significantly greater when it is taken in the morning.

Does Choleste cause weight gain?

Choleste may causes weight gain also with other side effects.

How long should I take Choleste?

Usually, treatment with a statin such as Choleste is for life. The benefits will only continue for as long as you take it.

Can statins make me tired?

People taking statins reported increased levels of general fatigue and tiredness.

Who should I take Choleste

Take Choleste exactly as prescribed. Follow all directions on your prescription label. Never take this medicine in larger amounts, or for longer than prescribed. Taking too much of this medication may cause serious or life-threatening side effects.

What happens if I miss a dose of Choleste?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

How long can I safely take Choleste?

Choleste treatment with a statin such as Choleste is for life. The benefits will only continue for as long as you take it. If you stop taking Choleste without starting a different treatment, your cholesterol level may rise again.

What happens when I stop taking Choleste?

Choleste decrease mortality rates in patients with high cholesterol. They will help you live longer. Stopping your statin has been linked to increased risk for cardiovascular events and death in patients with coronary artery disease.

How long should I take Choleste?

Choleste should takethree to five hours of oral administration.Choleste may take one to two weeks of regular dosing before improvements in your cholesterol level are seen, and up to four weeks before the maximal cholesterol-lowering effects of rosuvastatin are apparent.

Can I take overdose of Choleste?

Overdose of Choleste is not considered to be life threatening, but to be safe, get help. You can also call a poison help hotline for directions on what to do.

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