ROSZET

ROSZET- rosuvastatin calcium and ezetimibe tablet
Althera Pharmaceuticals LLC

1 INDICATIONS AND USAGE

ROSZET is indicated in adults:

• As an adjunct to diet in patients with primary non-familial hyperlipidemia to reduce low-density lipoprotein cholesterol (LDL-C).
• Alone or as an adjunct to other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage and Administration Information

• Swallow ROSZET tablets whole at any time of day, with or without food. Do not crush, dissolve, or chew tablets.
• The dosage range is 5 mg/10 mg to 40 mg/10 mg once daily.
• The recommended dose of ROSZET depends on a patient’s indication for usage, LDL-C, and individual risk for cardiovascular events.
• The starting dosage for patients switching to ROSZET from co-administration of a statin and ezetimibe is based on an equivalent dose of rosuvastatin and 10 mg of ezetimibe.
• Assess LDL-C when clinically appropriate, as early as 2 weeks after initiating ROSZET, and adjust the dosage if necessary.

2.2 Recommended Dosage in Asian Patients

Initiate ROSZET at 5 mg/10 mg daily due to increased rosuvastatin plasma concentrations. Consider the risk/benefit when treating Asian patients not adequately controlled at doses up to 20 mg/10 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.3)].

2.3 Recommended Dosage in Patients with Renal Impairment

In patients with severe renal impairment (CL_cr less than 30 mL/min/1.73 m²) not on hemodialysis, the recommended starting dosage is 5 mg/10 mg once daily and should not exceed 10 mg/10 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.

2.4 Dosage and Administration Modifications Due to Drug Interactions

• In patients taking a bile acid sequestrant, administer ROSZET at least 2 hours before or 4 hours after the bile acid sequestrant [see Drug Interactions (7.2)].
• When taking ROSZET with an aluminum and magnesium hydroxide combination antacid, administer ROSZET at least 2 hours before the antacid [see Drug Interactions (7.2)].
• Concomitant use of ROSZET with the following drugs requires dosage modifications of ROSZET [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

Darolutamide
Do not exceed ROSZET 5 mg/10 mg once daily.

Regorafenib
Do not exceed ROSZET 10 mg/10 mg once daily.

Antiviral MedicationsConcomitant use of sofosbuvir/velpatasvir/voxilaprevir and ledipasvir/sofosbuvir with ROSZET is not recommended.

In patients taking simeprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, atazanavir/ritonavir, and lopinavir/ritonavir initiate ROSZET at 5 mg/10 mg once daily. Do not exceed ROSZET 10 mg/10 mg once daily.

No dose adjustment is needed for concomitant use with fosamprenavir/ritonavir or tipranavir/ritonavir.

3 DOSAGE FORMS AND STRENGTHS

ROSZET tablets are available as follows:

Strength	Contents	Description
5 mg/10 mg	rosuvastatin 5 mg/ezetimibe 10 mg	round pink biconvex tablets with “5” embossed on one side
10 mg/10 mg	rosuvastatin 10 mg/ezetimibe 10 mg	round pink biconvex tablets with “AL” embossed on one side
20 mg/10 mg	rosuvastatin 20 mg/ezetimibe 10 mg	round pink biconvex tablets with “II” embossed on one side
40 mg/10 mg	rosuvastatin 40 mg/ezetimibe 10 mg	round pink biconvex tablets with “77” embossed on one side

4 CONTRAINDICATIONS

ROSZET is contraindicated in patients with:

• Acute liver failure or decompensated cirrhosis.
• Hypersensitivity to rosuvastatin, ezetimibe, or any excipients in ROSZET. Hypersensitivity reactions including anaphylaxis, angioedema, and erythema multiforme have been reported [see Adverse Reactions (6)].

5 WARNINGS AND PRECAUTIONS

5.1 Myopathy and Rhabdomyolysis

ROSZET may cause myopathy (muscle pain, tenderness, or weakness with creatine kinase [CK] above ten times the upper limit of normal) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin.

Risk Factors for Myopathy
Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs including other lipid-lowering therapies, and higher ROSZET dosage; Asian patients on ROSZET may be at higher risk for myopathy [see Drug Interactions (7.1) and Use in Specific Populations (8.8)]. The myopathy risk is greater in patients taking ROSZET 40 mg/10 mg daily compared with lower ROSZET dosages.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis
The concomitant use of ROSZET with cyclosporine or gemfibrozil is not recommended. ROSZET dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [see Dosage and Administration (2.4)]. Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions (7.1)].

Discontinue ROSZET if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if ROSZET is discontinued. Temporarily discontinue ROSZET in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the ROSZET dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

5.2 Immune-Mediated Necrotizing Myopathy

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; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Consider risk of IMNM carefully prior to initiation of a different statin. If therapy is initiated with a different statin, monitor for signs and symptoms of IMNM.