|Composition||Rosuvastatin 10 / 5mg+ Vitamin D3 1000 IU Tablets|
|Mechanism of Action||
Rosuvastatin is a selective and competitive inhibitor of HMG-coareductase, the rate-limiting enzyme in cholesterol synthesis. It increases the number of hepatic LDL receptors on the cell surface, enhancing uptake and catabolism of LDL. It also decreases apolipoprotein B, triglycerides and increases HDL.
Vit. D3: may have anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant & mood-modulatory activities. Along with parathyroid hormone & calcitonin, regulate serum calcium conc.
Absorption: Incompletely absorbed from the GI tract. Time to peak plasma concentration: Approx 5 hr. Absolute bioavailability: Approx 20%.
Distribution: Volume of distribution: 134 L. Plasma protein binding: Approx 90%.
Metabolism: Limited metabolism via CYP2C9 isoenzyme.
Excretion: Via faeces (approx 90%); urine (approx 5% as unchanged drug). Elimination half-life: Approx 19 hr.
Vitamin D: Onset: Slow. Duration: Relatively prolonged duration of action.
Absorption: Well absorbed from the GI tract. Presence of bile is essential for adequate intestinal absorption. Hence absorption may be decreased in patients with decreased fat absorption.
Distribution: Bound to a specific α-globulin. Can be stored in adipose & muscle tissue for long periods of time. Slowly released from storage sites & skin where it is formed in the presence of sunlight or uv light. May distribute into breast milk.
Metabolism: Hydroxylated in the liver by the enzyme vitamin D 25-hydroxylase to form 25-hydroxycholecalciferol (calcifediol). Further hydroxylated in the kidneys by the enzyme vitamin D1-hydroxylase to form the active metabolites 1,25-dihydroxycholecalciferol (calcitriol). Further metabolism also occurs in the kidneys, including the formation of the 1,24,25-trihydroxy derivatives.
Excretion: Mainly in the bile & faeces with only small amounts appearing in urine.
Rosuvastatin: Headache, dizziness, constipation, nausea, vomiting, abdominal pain, myalgia, chest pain, peripheral oedema, depression, insomnia, rash, paraesthesia, asthenia, abnormal LFT, elevated serum transaminase levels. Potentially Fatal: Severe rhabdomyolysis w/ acute renal failure. Hepatitis, pancreatitis. Rare: Stevens-Johnson syndrome, anaphylaxis, toxic epidermal necrolysis.
Vitamin D3 :Hyperphosphataemia or hypercalcaemia (in excessive intake). Associated effects of hypercalcaemia include hypercalciuria, ectopic calcification, & renal & CV damage.
Rosuvastatin: Patients w/ predisposing factors for myopathy (e.g. Untreated hypothyroidism, renal impairment), history of chronic liver disease and alcoholism. Monitoring Parameters Monitor creatine kinase (CK) periodically and LFT. Discontinue treatment if there is significant or persistent increase in CK levels, serum aminotransferase levels or evidence of myopathy.
Vitamin D: Excessive intake may lead to development of hyperphosphataemia or hypercalcaemia. Infants, renal impairment or calculi, heart disease. Monitor plasma phosphate & calcium level. Pregnancy, lactation.
Rosuvastatin: Adult: PO Hyperlipidaemias; Prophylaxis of CV events in high-risk patients Initial: 5 or 10 mg/day, may increase at 4-wk intervals to 20 mg/day if needed. Max: 40 mg/day.