Rosuvastatin-Ezetimibe

Rosuvastatin-Ezetimibe is a combination medication used as an adjunct to diet for primary nonfamilial hyperlipidemia to reduce LDL-C (low-density lipoprotein-cholesterol).

• Rosuvastatin-Ezetimibe is available under the following different brand names: Roszet 

Common side effects of Rosuvastatin-Ezetimibe include:

• Headache
• Nausea
• Muscle aches and pains
• Weakness
• Constipation
• Common cold and flu
• Diarrhea
• Dizziness
• Joint pain
• Stomach pain
• Runny nose and sore throat
• Tiredness
• Pain (back, hands, legs)

Serious side effects of Rosuvastatin-Ezetimibe include:

• Unexplained muscle pain, tenderness, or weakness (especially if you also have a fever);
• Upper stomach pain, and loss of appetite.
• Severe weakness or tiredness.
• Dark-colored urine; or
• Jaundice (yellowing of the skin or eyes).

Rare side effects of Rosuvastatin-Ezetimibe include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 5 mg/10 mg
• 10 mg/10 mg
• 20 mg/10 mg
• 40 mg/10 mg

Hyperlipidemia

Adult dosage

• Dosage range: Rosuvastatin-Ezetimibe 10mg/10mg to 40mg/10mg orally once a day
• Recommend this dosage depending on the indication, LDL-C, and individual risk for cardiovascular events
• Switching to rosuvastatin-Ezetimibe from coadministration of a statin and ezetimibe: Starting dose determined by rosuvastatin dose plus ezetimibe 10 mg

Homozygous Familial Hypercholesterolemia

Adult dosage

• Dosage range: Rosuvastatin-Ezetimibe 10mg/10mg to 40mg/10mg orally once a day
• Recommended dosage depends on the indication, LDL-C, and individual risk for cardiovascular events
• Switching to rosuvastatin-Ezetimibe from coadministration of a statin and ezetimibe: Starting dose determined by rosuvastatin dose plus ezetimibe 10 mg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Rosuvastatin-Ezetimibe has severe interactions with the following drugs:
  • gemfibrozil
  • red yeast rice
• Rosuvastatin-Ezetimibe has serious interactions with at least 21 other drugs.
• Rosuvastatin-Ezetimibe has moderate interactions with at least 61 other drugs.
• Rosuvastatin-Ezetimibe has minor interactions with the following drugs:
  • coenzyme Q10
  • colestipol
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • ethinylestradiol
  • fenofibrate
  • fenofibrate micronized
  • fenofibric acid
  • gemfibrozil
  • isradipine
  • mestranol
  • orlistat
  • trazodone
  • voclosporin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Acute liver failure or decompensated cirrhosis.
• Hypersensitivity to rosuvastatin, ezetimibe, or any excipients in drug product(s)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Rosuvastatin-Ezetimibe?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Rosuvastatin-Ezetimibe?”

Cautions

• Increased fasting blood glucose and glycosylated hemoglobin (HbA1c) levels are reported with statin intake; in some instances, these increases may exceed the threshold for the diagnosis of diabetes mellitus; optimize lifestyle measures, including regular exercise, maintaining healthy body weight, and making healthy food choices
• Hematuria and proteinuria were reported in clinical trials; findings were more frequent with rosuvastatin 40 mg compared to lower doses of rosuvastatin or other statins; effects are generally transient and were not associated with worsening renal function; consider dosage reduction if unexplained hematuria and proteinuria persists
• Myopathy and rhabdomyolysis
  • May cause myopathy (muscle pain, tenderness, or weakness with creatinine kinase [CK] above 10x ULN) and rhabdomyolysis
  • Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin
  • Risk factors: Age above 65 years, uncontrolled hypothyroidism, renal impairment, concurrent use with certain other drugs including other lipid-lowering therapies, higher rosuvastatin-Ezetimibe dosage, or patients of Asian descent or ethnicity
  • Discontinue if markedly elevated CK levels occur or myopathy is diagnosed or suspected; muscle symptoms and CK increases may resolve if therapy is discontinued
  • Temporarily withhold in patients with an acute, serious condition at high risk of developing renal failure secondary to rhabdomyolysis (. g, sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures)
  • Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing dosage
  • Instruct to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever
• Immune-mediated necrotizing myopathy
  • Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, reported with statin use
  • IMNM is characterized by
• Proximal muscle weakness
  • Elevated serum CK, which persists despite discontinuation of statin treatment
  • Positive anti-HMG CoA reductase antibody
  • Muscle biopsy showing necrotizing myopathy
  • Improvement with immunosuppressive agents
  • Treatment with immunosuppressive agents may be required
  • Additional neuromuscular and serologic testing may be necessary
  • Treatment with immunosuppressive agents may be required
  • Consider the risk of IMNM carefully before initiation of a different statin
  • If initiated with a different statin, monitor for signs and symptoms of IMNM
• Hepatic dysfunction
  • Increases in serum transaminases have occurred
  • In most cases, elevations appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy
  • Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury
  • Consider liver enzyme testing before initiation and thereafter, when clinically indicated.
  • Contraindicated in patients with acute liver failure or decompensated cirrhosis
  • If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue treatment
• Drug interaction overview
  • Rosuvastatin a substrate of CYP2C9 and transporters (.g, OATP1B1, BCRP)
  • Cyclosporine or gemfibrozil
  • Avoid coadministration
  • Cyclosporine increased rosuvastatin exposure 7-fold
  • In addition, ezetimibe and cyclosporine used concomitantly can increase exposure to both ezetimibe and cyclosporine
  • Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone
  • Concurrent use with cyclosporine or gemfibrozil may increase the risk of myopathy and rhabdomyolysis
• Antiviral medications
  • Avoid coadministration
  • Rosuvastatin plasma levels were significantly increased with the coadministration of many antiviral drugs, which increases the risk of myopathy and rhabdomyolysis
• Darolutamide and regorafenib
  • Reduce rosuvastatin-Ezetimibe dose
  • Darolutamide increased rosuvastatin exposure more than 5-fold and increased the risk of myopathy and rhabdomyolysis
  • Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy
• Fenofibrates and niacin
  • Consider benefits outweigh the increased risk of myopathy and rhabdomyolysis; monitor for signs and symptoms of myopathy during initiation and during up-titration of either fenofibrate, niacin, or rosuvastatin-Ezetimibe
  • Cases of myopathy and rhabdomyolysis have occurred with concomitant use of niacin with rosuvastatin
  • Fibrates may cause myopathy when given alone and may increase the risk of myopathy and rhabdomyolysis when administered with rosuvastatin-Ezetimibe use
• Antacids and bile acid sequestrants
  • Administer rosuvastatin-Ezetimibe at least 2 hr before or at least 4 hr after the bile acid sequestrant
  • Administer at least 2 hr before an aluminum and magnesium hydroxide combination antacid
  • Cholestyramine administration decreased the mean exposure of total ezetimibe by approximately 55%
  • Aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin by 50% and total ezetimibe by 4%
  • Incremental LDL-C reduction due to adding ezetimibe may be attenuated by coadministration with cholestyramine or an antacid combination
• Warfarin
  • Obtain an INR before starting and frequently after initiation, dose titration, or discontinuation to ensure that no significant alteration in INR occurs; once INR is stable, monitor INR at regularly recommended intervals
  • Rosuvastatin significantly increased INR in patients receiving vitamin K-depleting anticoagulants

Pregnancy and Lactation

• Owing to HMG-CoA reductase inhibitors decreasing cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, fetal harm may occur when administered to pregnant females; discontinue therapy as soon as pregnancy is recognized; limited published data are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage
• Contraception
  • Advise females of reproductive potential to use effective contraception during treatment
• FDA MedWatch
  • On July 20, 2021, the FDA requested to remove the contraindication against HMG-CoA reductase inhibitors in pregnant females
  • Despite the changes, most females found to be pregnant should stop therapy
• Lactation
  • There is no available information on the effects of the drug on the breastfed infant or milk production
  • Unknown whether is present in human milk; it has been shown that drugs in this class pass into human milk and atorvastatin are present in rat milk
  • Not recommended during treatment
  • FDA MedWatch
    • On July 20, 2021, the FDA requested to remove the contraindication against HMG-CoA reductase inhibitors in pregnant females
    • Breastfeeding is still not recommended if taking statins; the drug may still pass through the milk and pose a risk to breastfed children
    • For patients with lower risk, temporarily stop statin therapy until breastfeeding ends
    • Patients who are at high risk of heart attack or stroke and who require statins after delivery should not breastfeed and should use alternatives such as infant formula