Rosuvastatin+ Ezetimibe

Rosuvastatin + Ezetimibe combination lowers cholesterol through two different mechanisms of action. Rosuvastatin is a statin that reduces cholesterol production in the liver by blocking the HMG-CoA reductase enzyme. Ezetimibe is a cholesterol absorption inhibitor that blocks the absorption of dietary cholesterol from the small intestine. This dual mechanism is highly effective in lowering LDL cholesterol, especially in patients who do not respond to single therapy. It is convenient for once-daily dosing and represents a modern approach to managing high cholesterol.

• Primary Non-familial Hyperlipidemia: As an adjunct to diet to reduce LDL-C. • Homozygous Familial Hypercholesterolemia (HoFH): Alone or as an adjunct to other LDL-C-lowering therapies to reduce LDL-C.

Other lipid regulating drugs

Rosuvastatin: Rosuvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Rosuvastatin reduces LDL production and the number of LDL particles. 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, which is involved in the intestinal uptake of cholesterol and phytosterols.

Rosuvastatin + Ezetimibe combination works through two distinct mechanisms: Rosuvastatin: Blocks HMG-CoA reductase enzyme in the liver to reduce cholesterol production and increases LDL receptors to enhance LDL removal. Ezetimibe: Blocks Niemann-Pick C1-Like 1 (NPC1L1) protein in the small intestine to prevent absorption of dietary cholesterol. This dual mechanism creates a synergistic effect in lowering LDL cholesterol, which is more effective than single therapy.

• General Patients: 5/10 mg to 40/10 mg once daily; maximum dose is 40/10 mg once daily. Dose depends on the indication, LDL-C level, and cardiovascular risk. • Severe Renal Impairment (CrCl <30 mL/min) – Not on Hemodialysis: 5/10 mg once daily; maximum dose is 10/10 mg once daily. • Elderly Patients: No dosage adjustment is necessary. • Pediatric Patients: Safety and efficacy have not been established.

• Swallow the tablet whole. Do not crush, dissolve, or chew. • Can be taken with or without food. • With Bile Acid Sequestrants (e.g., Colestyramine): Administer at least 2 hours before or 4 hours after taking this medicine. • With Aluminium and Magnesium Hydroxide Antacids: Administer this medicine at least 2 hours before taking the antacid.

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

• Headache • Nausea • Myalgia (Muscle pain) • Arthralgia (Joint pain) • Dizziness • Asthenia (Weakness) • Constipation • Abdominal pain • Respiratory tract infection • Diarrhea • Sinusitis • Pain in extremity • Fatigue • Influenza • Back pain Serious Side Effects (Rare – Consult Doctor): • Myopathy and Rhabdomyolysis (muscle breakdown) • Elevated liver enzymes • Hepatic failure (rare)

Myopathy and Rhabdomyolysis: • Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher dosage. • Discontinue the medicine if markedly elevated creatine kinase (CK) levels occur or if myopathy is diagnosed or suspected. • Temporarily discontinue the medicine in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Hepatic Dysfunction: • Increases in serum transaminases may occur, and some cases may be persistent. • Rare reports of fatal and non-fatal hepatic failure have been reported. • Consider liver enzyme testing before initiating therapy and as clinically indicated thereafter.

• Active liver disease or decompensated cirrhosis. • Hypersensitivity to Rosuvastatin, Ezetimibe, or any of its components. • Women who are or may become pregnant. • Breastfeeding.

• Cyclosporine: Increases exposure. Concomitant use is not recommended. • Gemfibrozil: Increases exposure. Concomitant use is not recommended. • Antiviral drugs (e.g., Darunavir, Lopinavir/Ritonavir): Increase Rosuvastatin levels. Dose modification is recommended. • Darolutamide: Increases Rosuvastatin levels. Dose modification is recommended. • Regorafenib: Increases Rosuvastatin levels. Dose modification is recommended. • Niacin: Increases the risk of myopathy and rhabdomyolysis. Caution is required. • Fibrates (Fenofibrate): Increase the risk of myopathy and rhabdomyolysis. Caution is required. • Colchicine: Increases the risk of myopathy and rhabdomyolysis. Caution is required.

Caution is advised when consuming alcohol with this combination. Alcohol may put extra strain on the liver and increase the risk of liver problems. Grapefruit juice is safe with Rosuvastatin (compared to other statins), but consume in moderation. Avoid high-fat foods. A healthy diet (green leafy vegetables, fruits, whole grains) enhances the effectiveness of the medicine.

This combination is contraindicated during pregnancy. It can harm the developing baby. Inform your doctor if you are pregnant, planning pregnancy, or suspect pregnancy, and stop the medicine immediately. Do not use this medicine at any stage of pregnancy.

Breastfeeding is not recommended while taking this combination. Another drug in this class is known to pass into breast milk. Do not use this medicine while breastfeeding. If treatment is essential, consult your doctor for an alternative.

Safety and effectiveness have not been established in pediatric patients. Data on use in patients under 18 years is limited. Consult a pediatrician.

No dosage adjustment is necessary for elderly patients. However, patients over 65 years may have a higher risk of muscle problems, so regular monitoring is recommended.

Renal Impairment: Severe Renal Impairment (CrCl <30 mL/min/1.73 m²) – not on hemodialysis: Recommended starting dose is 5/10 mg once daily, maximum 10/10 mg once daily. Mild and Moderate Renal Impairment: No dosage adjustment recommendations. Hepatic Impairment: Acute liver failure or decompensated cirrhosis: Contraindicated. If serious hepatic injury with clinical symptoms occurs (hyperbilirubinemia or jaundice), discontinue the medicine.

There is no specific treatment in the event of overdose. Overdose may cause muscle pain, muscle weakness, nausea, diarrhea, and liver problems. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Contact a doctor immediately if you take an excessive dose.

Store below 30°C, protected from light and moisture. Keep out of reach of children. Do not use after the expiry date.