Razel D

Uses

Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun.

Vitamin D with calcium is used to treat or prevent bone loss (osteoporosis). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth.

Primary hypercholesterolemia (type IIa including heterozygous familial hypercholesterolemia), mixed dyslipidemia (type IIb), or homozygous familial hypercholesterolemia in patients who have not responded adequately to diet and other appropriate measures; prevention of cardiovascular events in patients at high risk of a first cardiovascular event.

Razel D is also used to associated treatment for these conditions: Calcium and Vitamin D Deficiencies, Deficiency of Vitamin D3, Deficiency, Vitamin A, Deficiency, Vitamin D, Fracture Bone, Hip Fracture, Hypoparathyroidism, Hypophosphatemia, Familial, Menopause, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Vertebral Fractures, Vitamin D Resistant Rickets, Vitamin Deficiency, Severe Bone Resorption, Spine fracture, Calcium supplementation, Nutritional supplementation, Vitamin D Supplementation, Vitamin supplementationAtherosclerosis, Atherosclerotic Cardiovascular Diseases, Cardiovascular Disease (CVD), Cardiovascular Events, Dysbetalipoproteinemia, Heterozygous Familial Hypercholesterolemia, High Blood Pressure (Hypertension), High Cholesterol, Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Hypertriglyceridemias, Major Adverse Cardiovascular Events, Mixed Dyslipidemias, Postoperative Thromboembolism, Primary Hypercholesterolemia, Primary Hyperlipidemia, Cardiovascular Primary Prevention, Lipid-Lowering Therapy

How Razel D works

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight .

Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease . Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone . Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus . This enhanced mobilization of skeletal calcium leads towards porotic bone conditions .

Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet . At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation . This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma .

In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively . Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts . Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels . Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys .

Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements . When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome . It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency . In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions .

Rosuvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL.

In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.

Statins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.

Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration. The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts. Rosuvastatin increases the bioavailability of nitric oxide by upregulating NOS and by increasing the stability of NOS through post-transcriptional polyadenylation. It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.

Dosage

Razel D dosage

Oral solution: Colecalciferol (Vitamin D3) is recommended 5-10 mcg or 1-2ml (200-400 IU)/day or as directed by the physician.

Chewable tablet: Cholecalciferol (Vitamin D3) is recommended 100 IU (1 tablet) daily, or as directed by physician. Take the medicine with food or within 1 hour after a meal. Place the tablet in mouth swallow after chewing.

Injection:

• Treatment of Cholecalciferol deficiency: 40,000 lU/week for 7 weeks, followed by maintenance therapy (1400-2000 lU/day). Follow-up 25 (OH) D measurements should be made approximately 3 to 4 months after initiating maintenance therapy to confirm that the target level has been achieved.
• Prevention of Vitamin D deficiency: 20,000 lU/Month.
• Treatment of Vitamin D deficiency:12-18 years: 20,000 IU, once every 2 weeks for 6 weeks. Prevention of Vitamin D deficiency, 12-18 years: 20,000 IU, once every 6 weeks.

Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment. The dose should be individualized according to the goal of therapy and patient response, using current consensus guidelines.

Treatment of hypercholesterolemia: Patient of Asian origin or with risk factors for myopathy or rhabdomyolysis: initially 5 mg once daily increased if necessary to max. 20 mg daily.

Prevention of cardiovascular events: Patient of Asian origin or with risk factors for myopathy or rhabdomyolysis: initially 5 mg once daily increased if necessary to max. 20 mg daily.

Pediatric Use (Hyperlipidemia including familial hypercholesterolemia):

• Child younger than 6 years: not recommended.
• Child 6–9 years: initially 5 mg daily, increased if necessary at intervals of at least 4 weeks to usual max. 10 mg once daily.
• Child 10–18 years: initially 5 mg daily, increased if necessary at intervals of at least 4 weeks to usual max. 20 mg once daily.

[Reduced dose required with concomitant atazanavir, darunavir, ezetimibe, fibrate, itraconazole, lopinavir, or tipranavir]

Use in the elderly (>70 years): A start dose of 5 mg is recommended. No dose adjustment necessary.

Renal insufficiency:Initially 5mg once daily (do not exceed 20 mg daily) if eGFR is 30-60 mL/minute/1.73 m2. Avoid if eGFR is less than 30 mL/minute/1.73 m2

Hepatic impairment:

• Child-Pugh scores of <7: no increase in systemic exposure to rosuvastatin.
• Child-Pugh scores of 8 and 9: increased systemic exposure has been observed. In these patients an assessment of renalfunction should be considered.
• Child-Pugh scores >9: no study.

Rosuvastatin is contraindicated in patients withactive liver disease.

Race: Increased systemic exposure has been seen in Asian subjects. The recommended starting dose is 5 mg for patients of Asian ancestry. The 40 mg dose is contraindicated in these patients.

Genetic polymorphisms: Specific types of genetic polymorphisms are known that can lead to increased rosuvastatin exposure. For patients who are known to have such specific types of polymorphisms, a lower daily dose of Rosuvastatin is recommended.

Dosage in patients with pre-disposing factors to myopathy: The recommended starting dose is 5 mg in patients with predisposing factors to myopathy. The 40 mg dose is contraindicated in some of these patients.

Rosuvastatin may be given at any time of day, with or without food

Side Effects

Generally all nutritional supplements are considered to be safe and well tolerable. However, few side-effects can generally occur including hypercalcaemia syndrome or Calcium intoxication (depending on the severity and duration of hypercalcaemia), occasional acute symptoms include anorexia, headache, nausea, vomiting, abdominal pain or stomach ache and constipation with the administration of Colecaciferol.

Common or very common: Proteinuria.

Rare: Hepatitis, jaundice.

Very rare: Gynecomastia, hematuria, hepati failure, interstitial lung disease, lupus erythematosus-like reactions, pancreatitis.

Frequency not known: Alopecia, altered liver function tests, amnesia, arthralgia, asthenia, depression, dizziness, edema, fatigue, gastrointestinal disturbances, headache, hypersensitivity reactions, hyperglycemia -may be associated with the development of diabetes mellitus (particularly in those already at risk of the condition), myalgia, myopathy, myositis, paresthesia, peripheral neuropathy, pruritus, rash, rhabdomyolysis, sexual dysfunction, sleep disturbance, Stevens-Johnson syndrome, thrombocytopenia, urticaria, visual disturbance.

Muscle effects: The risk of myopathy, myositis, and rhabdomyolysis associated with statin use is rare. Although myalgia has been reported commonly in patients receiving statins, muscle toxicity truly attributable to statin use is rare. Muscle toxicity can occur with all statins, however the likelihood increases with higher doses If muscular symptoms or raised creatine kinase occur during treatment, other possible causes (e.g. rigorous physical activity, hypothyroidism, infection, recent trauma, and drug or alcohol addiction) should be excluded before statin therapy is implicated, particularly if statin treatment has previously been tolerated for more than 3 months. When a statin is suspected to be the cause of myopathy, and creatine kinase concentration is markedly elevated (more than 5 times upper limit of normal), or if muscular symptoms are severe, treatment should be discontinued. If symptoms resolve and creatine kinase concentrations return to normal, the statin should be reintroduced at a lower dose and the patient monitored closely; an alternative statin should be prescribed if unacceptable side-effects are experienced with a particular statin. Statins should not be discontinued in the event of small, asymptomatic elevations of creatine kinase. Routine monitoring of creatine kinase is unnecessary in asymptomatic patients.Statins should not be discontinued if there is an increase in the blood-glucose concentration or HbA1C as the benefits continue to outweigh the risks.

Interstitial lung disease: If patients develop symptoms such as dyspnoea, cough, and weight loss, they should seek medical attention.

Toxicity

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae . Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia . Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures .

Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established . Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus, and other effects . Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures .

Vitamin D is deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of Vitamin D3 in excess of 10 µg daily should not be administered daily to nursing women.

Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered. Pharmacokinetic studies show an approximately two-fold increase in peak plasma concentration and AUC in Asian patients (Philippino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian descent) compared to Caucasian patients.

Precaution

People with the following conditions should exercise caution when considering taking vitamin D supplements: High blood Calcium or Phosphorus level, Heart problems, Kidney disease.

Vitamin D must be taken with adequate amounts of both Calcium and Magnesium supplementation. When Calcium level is low (due to insufficient vitamin D and calcium intake), the body activates the parathyroid gland, which produces PTH (parathyroid hormone). This hormone kick starts vitamin D hormone production and assists removal of Calcium from the bones to be used in more important functions such as neutralizing body acidity.

Hypothyroidism should be managed adequately before starting treatment with a statin. Statins should be used with caution in those with a history of liver disease or with a high alcohol intake. There is little information available on a rational approach to liver-function monitoring; however, a NICE guideline1 suggests that liver enzymes should be measured before treatment, and repeated within 3 months and at 12 months of starting treatment, unless indicated at other times by signs or symptoms suggestive of hepatotoxicity. Those with serum transaminases that are raised, but less than 3 times the upper limit of the reference range, should not be routinely excluded from statin therapy. Those with serum transaminases of more than 3 times the upper limit of the reference range should discontinue statin therapy.

Statins should be used with caution in those with risk factors for myopathy or rhabdomyolysis; patients should be advised to report unexplained muscle pain. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption should not take this medicine.

Interaction

Cholecalciferol is known to interact with Carbamazepine, Dactinomycin, Diuretics, Fosphenytoin, Miconazole, Phenobarbital, Phenytoin, Primidone

Cyclosporine: Cyclosporine increased rosuvastatin exposure (AUC) 7-fold. Therefore, in patients taking cyclosporine, the dose of Rosuvastatin should not exceed 5 mg once daily.

Gemfibrozil: Gemfibrozil significantly increased rosuvastatin exposure. Due to an observed increased risk of myopathy/rhabdomyolysis, combination therapy with Rosuvastatin and gemfibrozil should be avoided. If used together, the dose of Rosuvastatin should not exceed 10 mg once daily.

Protease Inhibitors: Coadministration of rosuvastatin with certain protease inhibitors has differing effects on rosuvastatin exposure. Simeprevir, which is a hepatitis C virus (HCV) protease inhibitor, or combinations of atazanavir/ritonavir or lopinavir/ritonavir, which are HIV-1 protease inhibitors, increase rosuvastatin exposure (AUC) up to threefold. For these protease inhibitors, the dose of Rosuvastatin should not exceed 10 mg once daily. The combinations of fosamprenavir / ritonavir or tipranavir / ritonavir, which are HIV 1 protease inhibitors, produce little or no change in rosuvastatin exposure. Caution should be exercised when rosuvastatin is coadministered with protease inhibitors.

Coumarin Anticoagulants: Rosuvastatin significantly increased INR in patients receiving coumarin anticoagulants. Therefore, caution should be exercised when coumarin anticoagulants are given in conjunction with Rosuvastatin. In patients taking coumarin anticoagulants and Rosuvastatin concomitantly, INR should be determined before starting Rosuvastatin and frequently enough during early therapy to ensure that no significant alteration of INR occurs.

Niacin: The risk of skeletal muscle effects may be enhanced when Rosuvastatin is used in combination with lipid-modifying doses (>1 g/day) of niacin; caution should be used when prescribing with Rosuvastatin.

Fenofibrate: When Rosuvastatin was coadministered with fenofibrate, no clinically significant increase in the AUC of rosuvastatin or fenofibrate was observed. Because it is known that the risk of myopathy during treatment with statins is increased with concomitant use of fenofibrates, caution should be used when prescribing fenofibrates with Rosuvastatin.

Colchicine: Cases of myopathy, including rhabdomyolysis, have been reported with statins, including rosuvastatin, coadministered with colchicine, and caution should be exercised when prescribing Rosuvastatin with colchicine

Volume of Distribution

Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L .

Rosuvastatin undergoes first-pass extraction in the liver, which is the primary site of cholesterol synthesis and LDL-C clearance. The mean volume of distribution at steady-state of rosuvastatin is approximately 134 litres.

Elimination Route

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal . Moreover, bile is necessary for absorption as well .

In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol .

In a study of healthy white male volunteers, the absolute oral bioavailability of rosuvastatin was found to be approximately 20% while absorption was estimated to be 50%, which is consistent with a substantial first-pass effect after oral dosing. Another study in healthy volunteers found that the peak plasma concentration (Cmax) of rosuvastatin was 6.06ng/mL and was reached at a median of 5 hours following oral dosing. Both Cmax and AUC increased in approximate proportion to dose. Neither food nor evening versus morning administration was shown to have an effect on the AUC of rosuvastatin. Many statins are known to interact with hepatic uptake transporters and thus reach high concentrations at their site of action in the liver.

Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein that plays an important role in the absorption of rosuvastatin, particularly as CYP3A4 has minimal involvement in its metabolism. Evidence from pharmacogenetic studies of c.421C>A single nucleotide polymorphisms (SNPs) in the gene for BCRP has demonstrated that individuals with the 421AA genotype have reduced functional activity and 2.4-fold higher AUC and Cmax values for rosuvastatin compared to study individuals with the control 421CC genotype. This has important implications for the variation in response to the drug in terms of efficacy and toxicity, particularly as the BCRP c.421C>A polymorphism occurs more frequently in Asian populations than in Caucasians. Other statin drugs impacted by this polymorphism include fluvastatin and atorvastatin.

Genetic differences in the OATP1B1 (organic-anion-transporting polypeptide 1B1) hepatic transporter have also been shown to impact rosuvastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C SNP showed that rosuvastatin AUC was increased 1.62-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals. Other statin drugs impacted by this polymorphism include simvastatin, pitavastatin, atorvastatin, and pravastatin.

For patients known to have the above-mentioned c.421AA BCRP or c.521CC OATP1B1 genotypes, a maximum daily dose of 20mg of rosuvastatin is recommended to avoid adverse effects from the increased exposure to the drug, such as muscle pain and risk of rhabdomyolysis.

Half Life

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days .

Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals .

The elimination half-life (t½) of rosuvastatin is approximately 19 hours and does not increase with increasing doses.

Clearance

Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day .

Elimination Route

It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces .

Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.

A study in healthy adult male volunteers found that approximately 90% of the rosuvastatin dose was recovered in feces within 72 hours after dose, while the remaining 10% was recovered in urine. The drug was completely excreted from the body after 10 days of dosing. They also found that approximately 76.8% of the excreted dose was unchanged from the parent compound, with the remaining dose recovered as the metabolites n-desmethyl rosuvastatin and rosuvastatin-5S-lactone.

Renal tubular secretion is responsible for >90% of total renal clearance, and is believed to be mediated primarily by the uptake transporter OAT3 (Organic anion transporter 1), while OAT1 had minimal involvement.

Pregnancy & Breastfeeding use

There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses. Colecalciferol should be used during pregnancy only if the benefits outweigh the potential risk to the fetus.

It should be assumed that exogenous Colecalciferol passes into the breast milk. In view of the potential for hypercalcaemia in the mother and for adverse reactions from Colecalciferol in nursing infants, mothers may breastfeed while taking Colecalciferol, provided that the serum Calcium levels of the mother and infant are monitored.

Pregnancy Category X. Teratogenic effects. Rosuvastatin is contraindicated in pregnancy and lactation. Women of child bearing potential should use appropriate contraceptive measures. If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.

Rosuvastatin is excreted in the milk of rats. There are no data with respect to excretion in milk in humans

Contraindication

Colecalciferol is contraindicated in all diseases associated with hypercalcaemia. It is also contraindicated in patients with known hypersensitivity to Colecalciferol (or medicines of the same class) and any of the constituent excipients. Colecalciferol is contraindicated if there is evidence of vitamin D toxicity.

Rosuvastatin is contraindicated:

• In patients with hypersensitivity to rosuvastatin or to any of the excipients.
• In patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN).
• In patients with severe renal impairment (creatinine clearance < mL/minute/1.73m2).
• In patients with myopathy.
• In patients receiving concomitant cyclosporine.
• During pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.

Special Warning

Age and sex: There was no clinically relevant effect of age or sex on the pharmacokinetics of Rosuvastatin in adults.

Race: Pharmacokinetic studies show an increase in exposure in Asian subjects compared with Caucasians.

Severe renal impairment (not on hemodialysis): Starting dose is 5 mg, not to exceed 10 mg

Use in the elderly: Patients > 70 years: A start dose of 5 mg is recommended. No dose adjustment necessary.

Renal insufficiency: Initially 5mg once daily (do not exceed 20mg daily) if eGFR is 30–60 mL/ minute/ 1.73 m2. Avoid if eGFR is less than 30 mL /minute/ 1.73 m2.

Genetic polymorphisms: Specific types of genetic polymorphisms are known that can lead to increased rosuvastatin exposure. For patients who are known to have such specific types of polymorphisms, a lower daily dose of Rosuvastatin is recommended.

Dosage in patients with pre-disposing factors to myopathy: The recommended starting dose is 5 mg in patients with predisposing factors to myopathy. The 40 mg dose is contraindicated in some of these patients.

Acute Overdose

Symptoms: anorexia, headache, vomiting, constipation, dystrophy (weakness, loss of weight), sensory disturbances, possibly fever with thirst, polyuria, dehydration, apathy, arrested growth and urinary tract infections. Hypercalcaemia ensues, with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.

Treatment: Immediate gastric lavage or induction of vomiting to prevent further absorption. Liquid paraffin should be administered to promote faecal excretion. Repeated serum calcium determinations are advisable. If elevated calcium levels persist in the serum, phosphates and corticosteroids may be administered and measures instituted to bring about adequate diuresis.

There is no specific treatment in the event of overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Haemodialysis is unlikely to be of benefit.

Storage Condition

Keep out of the reach of children. Store below 30° C. Keep in the original package in a cool & dry place in order to protect from light and moisture.

Innovators Monograph

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