Rosuzet Special Precautions

As with other HMG-CoA reductase inhibitors, effects on skeletal muscle, e.g. myalgia, myopathy and, rarely, rhabdomyolysis, have been reported in patients treated with rosuvastatin. As with other HMG-CoA reductase inhibitors, the reporting rate for rhabdomyolysis in post-marketing use is higher at the highest marketed dose. Patients who develop any signs or symptoms suggestive of myopathy should have their CK levels measured. Ezetimibe + Rosuvastatin (ROSUZET) therapy should be discontinued if CK levels are markedly elevated (> 10 x ULN) or if myopathy is diagnosed or suspected. There have been very rare reports of an immune-mediated necrotising myopathy clinically characterized by persistent proximal muscle weakness and elevated serum creatine kinase during treatment or following discontinuation of statins, including rosuvastatin. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required.
In rosuvastatin trials there was no evidence of increased skeletal muscle effects when rosuvastatin was dosed with any concomitant therapy. However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with ciclosporin, fibric acid derivatives (including gemfibrozil), nicotinic acid, azole antifungals and macrolide antibiotics.
Ezetimibe + Rosuvastatin (ROSUZET) should be prescribed with caution in patients with pre-disposing factors for myopathy, such as, renal impairment, advanced age and hypothyroidism, or situations where an increase in plasma levels may occur (see Rosuvastatin under INTERACTIONS).
Ezetimibe + Rosuvastatin (ROSUZET) should be temporarily withheld in any patient with an acute serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
Reports of myopathy and/or rhabdomyolysis have been observed with HMG-CoA reductase inhibitors coadministered with daptomycin. Caution should be used when prescribing HMG-CoA reductase inhibitors with daptomycin, as either agent can cause myopathy and/or rhabdomyolysis when given alone. Consideration should be given to suspending Ezetimibe + Rosuvastatin (ROSUZET) temporarily in patients taking daptomycin [see Rosuvastatin under INTERACTIONS].
Liver Enzyme Abnormalities: In controlled coadministration trials in patients receiving ezetimibe with a statin, consecutive transaminase elevations (≥3X the upper limit of normal [ULN]) have been observed. (See ADVERSE REACTIONS).
In the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), 18,144 patients with CHD were randomized to receive ezetimibe/simvastatin 10/40 mg daily (n=9067) or simvastatin 40 mg daily (n=9077). During a median follow-up of 6.0 years, the incidence of consecutive elevations of transaminases (≥3 X ULN) was 2.5% for ezetimibe/simvastatin and 2.3% for simvastatin.
In a controlled clinical study in which over 9000 patients with chronic kidney disease were randomized to receive Ezetimibe (EZETROL) Tablet 10 mg combined with simvastatin 20 mg daily (n=4650) or placebo (n=4620) (median follow-up period of 4.9 years), the incidence of consecutive elevations of transaminases (≥3 X ULN) was 0.7% for Ezetimibe (EZETROL) Tablet combined with simvastatin and 0.6% for placebo.
Ezetimibe + Rosuvastatin (ROSUZET) should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.
Hepatic Impairment: Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic impairment, Ezetimibe + Rosuvastatin (ROSUZET) is not recommended in these patients.
Gemfibrozil: Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with Ezetimibe + Rosuvastatin (ROSUZET) and gemfibrozil should be avoided (see INTERACTIONS). If used together, the dose of Ezetimibe + Rosuvastatin (ROSUZET) should not exceed 10/10 mg once daily.
Fenofibrate: If cholelithiasis is suspected in a patient receiving Ezetimibe + Rosuvastatin (ROSUZET) and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered [see the product labeling for fenofibrate and fenofibric acid].
Other Fibrates: The coadministration of ezetimibe with fibrates other than fenofibrate has not been studied. Therefore, coadministration of Ezetimibe + Rosuvastatin (ROSUZET) and fibrates (other than fenofibrate) is not recommended (see INTERACTIONS).
Anticoagulants: If Ezetimibe + Rosuvastatin (ROSUZET) is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalized Ratio (INR) should be appropriately monitored (see INTERACTIONS).
Diabetes Mellitus: As with other HMG-CoA reductase inhibitors, increases in HbA1c and serum glucose levels have been observed in patients treated with rosuvastatin, and in some instances these increases may exceed the threshold for the diagnosis of diabetes mellitus, primarily in patients already at high risk for developing diabetes (see ADVERSE REACTIONS and PHARMACOLOGY under Actions).
Race: Pharmacokinetic studies show an increase in rosuvastatin exposure in Asian subjects compared with Caucasians (see Race under DOSAGE & ADMINISTRATION and PHARMACOLOGY: Pharmacokinetics under Actions).
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Pharmacology testing revealed no evidence of a sedative effect of rosuvastatin. From the safety profile, rosuvastatin is not expected to adversely affect the ability to drive or use machines.
Use in Children: There are insufficient data for the safe and effective use of Ezetimibe + Rosuvastatin (ROSUZET) in pediatric patients.