Roszet

Last reviewed on RxList: 4/1/2021
Roszet Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Roszet?

Roszet (rosuvastatin and ezetimibe) is a combination of an HMG CoA-reductase inhibitor (statin) and a dietary cholesterol absorption inhibitor indicated in adults either as an adjunct to diet in patients with primary non-familial hyperlipidemia to reduce low-density lipoprotein cholesterol (LDL¬C), or alone or as an adjunct to other LDL-C lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.

What Are Side Effects of Roszet?

Side effects of Roszet include:

Dosage for Roszet

The dosage of Roszet range is 5 mg/10 mg to 40 mg/10 mg once daily. The recommended dosage depends on the indication for usage, LDL¬C, and individual risk for cardiovascular events.

Roszet In Children

The safety and effectiveness of Roszet have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Roszet?

Roszet may interact with other medicines such as:

  • gemfibrozil,
  • cyclosporine,
  • certain antivirals,
  • darolutamide,
  • regorafenib,
  • fenofibrates,
  • niacin,
  • colchine,
  • bile acid sequestrants,
  • antacids, and
  • warfarin

Tell your doctor all medications and supplements you use.

Roszet During Pregnancy and Breastfeeding

Roszet is not recommended for use during pregnancy; it may harm a fetus. It is unknown if Roszet passes into breast milk. Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, breastfeeding is not recommended during treatment with Roszet.

Additional Information

Our Roszet (rosuvastatin and ezetimibe) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

How to Lower Your Cholesterol & Save Your Heart See Slideshow
Roszet Professional Information

SIDE EFFECTS

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

  • Myopathy and Rhabdomyolysis [see WARNINGS AND PRECAUTIONS]
  • Hepatic Dysfunction [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

Rosuvastatin

In double-blind, controlled (placebo-or active-controlled) clinical trials of rosuvastatin, 5394 patients with primary hyperlipidemia were treated for a duration of up to 12 weeks. Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 1.

Table 1: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and Greater than Placebo in Placebo-Controlled Trials

Adverse Reactions Placebo
(N=382) %
Total Rosuvastatin 5 mg-40 mg
(N=744) %
Headache 5.0 5.5
Nausea 3.1 3.4
Myalgia 1.3 2.8
Asthenia 2.6 2.7
Constipation 2.4 2.4

Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema), and pancreatitis.

In a double-blind, placebo-controlled trial with mean treatment duration of 1.7 years, 981 participants were treated with rosuvastatin 40 mg (n=700) or placebo (n=281). The most common adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.

Table 2: Adverse Reactions Occurring in ≥2% of Patients Treated with Rosuvastatin and Greater than Placebo

Adverse Reactions Placebo
(N=281) %
Rosuvastatin 40 mg
(N=700) %
Myalgia 12.1 12.7
Arthralgia 7.1 10.1
Headache 5.3 6.4
Dizziness 2.8 4.0
Increased CPK 0.7 2.6
Abdominal pain 1.8 2.4
ALT >3x ULN1 0.7 2.2
1 Frequency recorded as abnormal laboratory value.

In a double-blind, placebo-controlled trial with mean treatment duration of 2 years, 17,802 participants were treated with rosuvastatin 20 mg (n=8901) or placebo (n=8901). There was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with a HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated versus placebo-treated patients.

Laboratory Tests

The following laboratory abnormalities have been reported in clinical studies of rosuvastatin: dipstick-positive proteinuria and microscopic hematuria; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities.

Ezetimibe Monotherapy

In 10 double-blind, placebo-controlled clinical trials, 2396 patients with primary hyperlipidemia (50% women, 90% Caucasians, 5% Blacks, 3% Hispanics, 2% Asians) and elevated LDL-C were treated with ezetimibe for a median treatment duration of 12 weeks. Adverse reactions reported in ≥2% of patients treated with ezetimibe and at an incidence greater than placebo are shown in Table 3.

Table 3: Adverse Reactions Occurring in ≥2% of Patients Treated with Ezetimibe and Greaterthan Placebo in Placebo-Controlled Trials

Adverse Reactions Placebo
(N=1159) %
Ezetimibe
(N=2396) %
Upper respiratory tract infection 2.5 4.3
Diarrhea 3.7 4.1
Arthralgia 2.2 3.0
Sinusitis 2.2 2.8
Pain in extremity 2.5 2.7
Fatigue 1.5 2.4
Influenza 1.5 2.0

The incidence of consecutive elevations (≥3x ULN) in hepatic transaminase levels was similar between ezetimibe (0.5%) and placebo (0.3%).

Ezetimibe Combination With Statins

In 28 double-blind, controlled (placebo-or active-controlled) clinical trials, 11,308 patients with primary hyperlipidemia (48% women, 85% Caucasians, 7% Blacks, 4% Hispanics, 3% Asians) and elevated LDL-C were treated with ezetimibe concurrently with or added to ongoing statin therapy for a median treatment duration of 8 weeks. Clinical adverse reactions reported in ≥2% of patients treated with ezetimibe + statin and at an incidence greater than statin are shown in Table 4.

Table 4: Adverse Reactions Occurring in ≥2% of Patients Treated with Ezetimibe Coadministered with a Statin and at an Incidence Greater than Statin

Adverse Reactions All Statins1
(N=9361) %
Ezetimibe + All Statins1
(N=2396) %
Nasopharyngitis 3.3 3.7
Myalgia 2.7 3.2
Upper respiratory tract infection 2.8 2.9
Arthralgia 2.4 2.6
Diarrhea 2.2 2.5
Back pain 2.3 2.4
Influenza 2.1 2.2
Pain in extremity 1.9 2.1
Fatigue 1.6 2.0
1 All Statins = all doses of statins

The incidence of consecutive increased transaminases (≥3x ULN) was higher in patients receiving ezetimibe administered with statins (1.3%) than in patients treated with statins alone (0.4%). These elevations in transaminases were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of rosuvastatin and ezetimibe. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Rosuvastatin

Arthralgia, fatal and non-fatal hepatic failure, hepatitis, jaundice, thrombocytopenia, depression, sleep disorders (including insomnia and nightmares), peripheral neuropathy, interstitial lung disease and gynecomastia. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use. There have been rare post marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Ezetimibe

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria; erythema multiforme; arthralgia; myalgia; elevated creatine phosphokinase; myopathy/rhabdomyolysis; elevations in liver transaminases; hepatitis; abdominal pain; thrombocytopenia; pancreatitis; nausea; dizziness; paresthesia; depression; headache; cholelithiasis; cholecystitis.

DRUG INTERACTIONS

Drug Interactions That Increase The Risk Of Myopathy And Rhabdomyolysis With ROSZET

Rosuvastatin is a substrate of CYP2C9 and transporters (such as OATP1B1, BCRP). Rosuvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP2C9 and transporters. Table 5 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with ROSZET and instructions for preventing or managing them [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Table 5: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with ROSZET

Cyclosporine or Gemfibrozil
Clinical Impact: 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. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with ROSZET.
Intervention: Avoid concomitant use of cyclosporine or gemfibrozil with ROSZET.
Anti-Viral Medications
Clinical Impact: Rosuvastatin plasma levels were significantly increased with concomitant administration of many anti-viral drugs, which increases the risk of myopathy and rhabdomyolysis.
Intervention: Avoid concomitant use of sofosbuvir/velpatasvir/voxilaprevir and ledipasvir/sofosbuvir with ROSZET.
In patients taking simeprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, atazanavir/ritonavir, and lopinavir/ritonavir initiate with a dose of ROSZET 5 mg/10mg once daily, and do not exceed a dose of ROSZET 10 mg/10 mg once daily [see DOSAGE AND ADMINISTRATION].
No dose adjustment is needed for concomitant use with fosamprenavir/ritonavir or tipranavir/ritonavir.
Monitor all patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward titration of either drug.
Darolutamide
Clinical Impact: Darolutamide increased rosuvastatin exposure more than 5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use.
Intervention: In patients taking darolutamide, do not exceed a dose of ROSZET 5 mg/10 mg once daily [see DOSAGE AND ADMINISTRATION].
Regorafenib
Clinical Impact: Regorafenib increased rosuvastatin exposure and may increase the risk of myopathy.
Intervention: In patients taking regorafenib, do not exceed a dose of ROSZET 10 mg/10 mg once daily [see DOSAGE AND ADMINISTRATION].
Fenofibrates (e.g., fenofibrate and fenofibric acid)
Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with ROSZET.
Intervention: Consider if the benefit of using fibrates concomitantly with ROSZET outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.
Niacin
Clinical Impact: Cases of myopathy and rhabdomyolysis have occurred with concomitant use of niacin with rosuvastatin.
Intervention: Consider if the benefit of using niacin concomitantly with ROSZET outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.
Colchicine
Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with ROSZET
Intervention: Consider if the benefit of using colchicine concomitantly with ROSZET outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.

Drug Interactions That Decrease The Efficacy Of ROSZET

Table 6 presents drug interactions that may decrease the efficacy of ROSZET and instructions for preventing or managing them.

Table 6: Drug Interactions that Decrease the Efficacy of ROSZET

Bile Acid Sequestrants
Clinical Impact: Concomitant cholestyramine administration decreased the mean exposure of total ezetimibe approximately 55%. The incremental LDL-C reduction due to adding ezetimibe may be attenuated by coadminstration with cholestyramine. [see CLINICAL PHARMACOLOGY].
Intervention: In patients taking a bile acid sequestrant, administer ROSZET at least 2 hours before or at least 4 hours after the bile acid sequestrant [see DOSAGE AND ADMINISTRATION].
Antacid
Clinical Impact: Concomitant aluminum and magnesium hydroxide combination antacid administration decreased the mean exposure of rosuvastatin 50% and total ezetimibe 4%. The incremental LDL-C reduction due to adding ROSZET may be attenuated by coadministration with antacid. [see CLINICAL PHARMACOLOGY].
Intervention: In patients taking antacid, administer ROSZET 2 hours after the antacid [see DOSAGE AND ADMINISTRATION].

ROSZET Effects On Other Drugs

Table 7 presents ROSZET's effect on other drugs and instructions for preventing or managing them.

Table 7: ROSZET Effects on Other Drugs

Warfarin
Clinical Impact: Rosuvastatin significantly increased the INR in patients receiving coumarin anticoagulants [see CLINICAL PHARMACOLOGY].
Intervention: In patients taking warfarin, obtain an INR before starting ROSZET and frequently enough after initiation, dose titration or discontinuation to ensure that no significant alteration in INR occurs. Once the INR is stable, monitor INR at regularly recommended intervals.

Read the entire FDA prescribing information for Roszet (Rosuvastatin and Ezetimibe Tablets)

QUESTION

What is cholesterol? See Answer

© Roszet Patient Information is supplied by Cerner Multum, Inc. and Roszet Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors