Ezetimibe and Simvastatin

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Overview

What is Ezetimibe and Simvastatin?

Ezetimibe and simvastatin tablets contain ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and simvastatin, an HMG-CoA reductase inhibitor.

The chemical name of ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The molecular formula is CHFNO and its molecular weight is 409.4.

Ezetimibe, USP is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is:

Simvastatin, USP an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMG-CoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1-[1α,3α,7β,8β(2*,4*),-8aβ]]. The molecular formula of simvastatin is CHO and its molecular weight is 418.57.

Simvastatin, USP is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol. Its structural formula is:

Ezetimibe and simvastatin is available for oral use as tablets containing 10 mg of ezetimibe USP, and 10 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/10 mg), 20 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/20 mg), 40 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/40 mg), or 80 mg of simvastatin, USP (ezetimibe and simvastatin tablets 10 mg/80 mg). Each tablet contains the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, citric acid anhydrous, croscarmellose sodium, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and propyl gallate.

What does Ezetimibe and Simvastatin look like?

What are the available doses of Ezetimibe and Simvastatin?

• Ezetimibe and simvastatin tablets 10 mg/10 mg are light tan, slightly speckled, round, unscored, biconvex tablets debossed with on one side and on opposite side.

• Ezetimibe and simvastatin tablets 10 mg/20 mg are light tan, slightly speckled, round, unscored, biconvex tablets debossed with on one side and on opposite side.

• Ezetimibe and simvastatin tablets 10 mg/40 mg are light tan, slightly speckled, round, unscored, biconvex tablets debossed with on one side and on opposite side.

• Ezetimibe and simvastatin tablets 10 mg/80 mg are light tan, slightly speckled, capsule shaped, unscored, biconvex tablets debossed with on one side and on opposite side.

What should I talk to my health care provider before I take Ezetimibe and Simvastatin?

How should I use Ezetimibe and Simvastatin?

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate.

The usual dosage range is 10 mg/10 mg/day to 10 mg/40 mg/day. The recommended usual starting dose is 10 mg/10 mg/day or 10 mg/20 mg/day. Ezetimibe and simvastatin should be taken as a single daily dose in the evening, with or without food. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10 mg/40 mg/day in the absence of moderate to severe renal impairment (estimated glomerular filtration rate less than 60 mL/min/1.73 m). After initiation or titration of ezetimibe and simvastatin, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed.

What interacts with Ezetimibe and Simvastatin?

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What are the warnings of Ezetimibe and Simvastatin?

Sorry No Records found

What are the precautions of Ezetimibe and Simvastatin?

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What are the side effects of Ezetimibe and Simvastatin?

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What should I look out for while using Ezetimibe and Simvastatin?

Ezetimibe and simvastatin tablets are contraindicated in the following conditions:

What might happen if I take too much Ezetimibe and Simvastatin?

Ezetimibe

and

S

imvastatin

No specific treatment of overdosage with ezetimibe and simvastatin can be recommended. In the event of an overdose, symptomatic and supportive measures should be employed.

Ezetimibe

In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hyperlipidemia for up to 56 days, was generally well tolerated.

A few cases of overdosage have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious.

Simvastatin

Significant lethality was observed in mice after a single oral dose of 9 g/m. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.

A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.

The dialyzability of simvastatin and its metabolites in man is not known at present.

How should I store and handle Ezetimibe and Simvastatin?

Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.Ezetimibe and simvastatin tablets are supplied as follows:10 mg/10 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 10 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-565-30), and 90 (NDC 45963-565-08). 10 mg/20 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 20 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-566-30), and 90 (NDC 45963-566-08). 10 mg/40 mg – Each light tan, slightly speckled, round, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 40 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-567-30), and 90 (NDC 45963-567-08). 10 mg/80 mg – Each light tan, slightly speckled, capsule shaped, unscored, biconvex tablet debossed with on one side and on opposite side contains 10 mg of ezetimibe, USP and 80 mg of simvastatin, USP. Tablets are supplied in bottles of 30 (NDC 45963-568-30), and 90 (NDC 45963-568-08).Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Keep container tightly closed. Dispense in a tight, light-resistant container as defined in the USP.

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Clinical Information

Chemical Structure

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Clinical Pharmacology

Ezetimibe

and

S

imvastatin

Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin contains ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe and simvastatin reduces elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and increases HDL-C through dual inhibition of cholesterol absorption and synthesis.

Ezetimibe

Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. In a 2-week clinical study in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production.

Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of statins .

Simvastatin

Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces very-low-density lipoproteins (VLDL) and TG and increases HDL-C.

Non-Clinical Toxicology

Ezetimibe and simvastatin tablets are contraindicated in the following conditions:

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above ten times 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 elevated plasma levels of simvastatin and simvastatin acid. Predisposing factors for myopathy include advanced age (greater than or equal to 65 years), female gender, uncontrolled hypothyroidism, and renal impairment.

The risk of myopathy, including rhabdomyolysis, is dose related.

In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] greater than 10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK greater than 40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.

The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared

with

other

statin

therapies

with

similar

or

greater

LDL-C-lowering

efficacy

and compared with lower doses of simvastatin. Therefore, the

10 mg/

80-mg dose of

ezetimibe

and simvastatin

should be used only in patients who have been taking

ezetimibe

and simvastatin

10 mg/

80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity

. If, however, a patient who is currently tolerating the

10 mg/

80-mg dose of

ezetimibe

and simvastatin

needs to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction. Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately

.

In the Study of Heart and Renal Protection (SHARP), 9270 patients with chronic kidney disease were allocated to receive ezetimibe and simvastatin 10 mg/20 mg daily (n=4650) or placebo (n=4620). During a median follow-up period of 4.9 years, the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] greater than 10 times upper limit of normal [ULN]) was 0.2% for ezetimibe and simvastatin and 0.1% for placebo: the incidence of rhabdomyolysis (defined as myopathy with a CK greater than 40 times ULN) was 0.09% for ezetimibe and simvastatin and 0.02% for placebo.

In postmarketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe. However, rhabdomyolysis has been reported with ezetimibe monotherapy and with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibric acid derivatives. Ezetimibe and simvastatin and a fenofibrate, if taking concomitantly, should both be immediately discontinued if myopathy is diagnosed or suspected.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.

All patients starting therapy with

ezetimibe

and simvastatin

or whose dose of

ezetimibe

and simvastatin

is being increased should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing

ezetimibe

and simvastatin

.

Ezetimibe

and simvastatin

therapy should be discontinued immediately if myopathy is diagnosed or suspected.

Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients taking ezetimibe and simvastatin merit closer monitoring.

Ezetimibe and simvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Ezetimibe and simvastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.

Drug Interactions

The risk of myopathy and rhabdomyolysis is increased by elevated plasma levels of simvastatin and simvastatin acid. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, and voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, cobicistat-containing products, or grapefruit juice Combination of these drugs with ezetimibe and simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with ezetimibe and simvastatin must be suspended during the course of treatment

The combined use of ezetimibe and simvastatin with gemfibrozil, cyclosporine, or danazol is contraindicated .

Caution should be used when prescribing fenofibrates with ezetimibe and simvastatin, as these agents can cause myopathy when given alone and the risk is increased when they are coadministered .

Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing ezetimibe and simvastatin with colchicine .

The benefits of the combined use of ezetimibe and simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (fenofibrates, greater than or equal to 1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine .

Cases of myopathy, including rhabdomyolysis, have been observed with simvastatin coadministered with lipid-modifying doses (greater than or equal to 1 g/day niacin) of niacin-containing products. In an ongoing, double-blind, randomized cardiovascular outcomes trial, an independent safety monitoring committee identified that the incidence of myopathy is higher in Chinese compared with non-Chinese patients taking simvastatin 40 mg or ezetimibe and simvastatin 10 mg/40 mg coadministered with lipid-modifying doses of a niacin-containing product. Caution should be used when treating Chinese patients with ezetimibe and simvastatin in doses exceeding 10 mg/20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive ezetimibe and simvastatin 10 mg/80 mg coadministered with lipid-modifying doses of niacin-containing products. It is unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients .

Prescribing recommendations for interacting agents are summarized in Table 1 .

The following serious adverse reactions are discussed in greater detail in other sections of the label:

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Review

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Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

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Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).

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