Rosuvastatin/Crestor

Rosuvastatin is one of the most potent statins available in the UK, capable of producing LDL cholesterol reductions of 45 to 55 per cent at high doses, placing it firmly in the high intensity statin category recommended by NICE for most adults requiring cardiovascular risk reduction. Rosuvastatin tablets, available under the brand name Crestor and as generic products, are a prescription-only statin used in adults and children for cholesterol lowering and prevention of cardiovascular events. A prescription can only be issued following a clinical consultation.

Rosuvastatin tablets are an oral prescription medicine containing rosuvastatin calcium as the active ingredient. Rosuvastatin belongs to the statin class of lipid-lowering medicines and is classified as a high intensity statin at doses of 20 mg and above per NICE guideline NG238. Crestor is the originator brand manufactured by AstraZeneca; generic rosuvastatin is also widely available.

Rosuvastatin is licensed in the UK for the following indications: treatment of primary hypercholesterolaemia, mixed dyslipidaemia, and familial hypercholesterolaemia in adults and children; prevention of cardiovascular events in adults at elevated cardiovascular risk. The cardiovascular prevention indication is supported by evidence from the JUPITER trial, which demonstrated that rosuvastatin reduced cardiovascular events in patients with elevated CRP (a marker of inflammation) but near-normal LDL cholesterol. Rosuvastatin is also licensed specifically for homozygous familial hypercholesterolaemia alongside dietary measures and other lipid lowering treatments.

Rosuvastatin is available in four strengths: 5 mg, 10 mg, 20 mg, and 40 mg. The 5 mg strength is used as a starting dose in specific patient groups. The 40 mg strength is the maximum dose and is restricted to patients whose LDL has not been adequately controlled on lower doses.

Rosuvastatin lowers cholesterol through the same fundamental mechanism as all statins, HMG-CoA reductase inhibition, but achieves greater LDL reduction per milligram than most other statins in the class.

HMG-CoA Reductase Inhibition. Rosuvastatin selectively and competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. By reducing the liver's internal production of cholesterol, rosuvastatin causes liver cells to upregulate LDL receptors, capturing more LDL cholesterol from the bloodstream. The result is a significant fall in plasma LDL cholesterol. Rosuvastatin also reduces triglycerides and raises HDL cholesterol.

High Potency and CYP2C9 Metabolism. Rosuvastatin is a hydrophilic statin that achieves high potency partly because it has a strong binding affinity for HMG-CoA reductase. It is metabolised minimally and primarily by CYP2C9, unlike simvastatin and atorvastatin which are mainly CYP3A4 substrates. This means grapefruit juice does not significantly affect rosuvastatin levels. However, rosuvastatin is affected by certain CYP2C9 inhibitors and by medicines that affect OATP1B1 and OATP1B3 transporters such as ciclosporin.

At the 20 mg and 40 mg doses, rosuvastatin is classified as a high intensity statin per NICE guideline NG238, expected to reduce LDL cholesterol by 40 per cent or more from baseline. The 10 mg dose achieves somewhat less LDL reduction and may be considered medium intensity in some patients. NICE recommends high intensity statins for most adults eligible for cardiovascular risk reduction therapy.

Always take rosuvastatin exactly as your prescriber instructs. Read the Patient Information Leaflet supplied with your medicine before starting treatment.

• Take rosuvastatin once daily, at any time of day, with or without food.
• Swallow the tablet whole with a glass of water.
• Grapefruit juice does not significantly affect rosuvastatin and does not need to be avoided.
• Antacids containing aluminium and magnesium hydroxide should be taken at least two hours after rosuvastatin.

If you miss a dose, take it as soon as you remember. If you only remember the following day, skip the missed dose and continue as normal. Do not take two doses on the same day. Do not stop taking rosuvastatin without speaking to your prescriber first.

Your prescriber will arrange lipid level monitoring before starting and typically four to twelve weeks after. Liver function may also be checked.

Rosuvastatin is available in four strengths, each suited to different clinical scenarios and patient groups.

Rosuvastatin 5 mg Tablets: A cautious starting dose used in specific patient groups: patients of East Asian origin (Chinese, Japanese, Korean, Vietnamese, Filipino, and Indian patients), who have higher rosuvastatin plasma concentrations than Caucasian patients; patients with predisposing factors for myopathy such as personal or family history of muscle problems, kidney impairment, or hypothyroidism; and patients aged 70 and over as a starting dose. For all other adults, the standard starting dose is 5 mg or 10 mg.

Rosuvastatin 10 mg Tablets: The recommended starting dose for most adults without the risk factors listed above. Lipid response is reviewed after four to twelve weeks to determine whether a dose increase is needed.

Rosuvastatin 20 mg Tablets: A high intensity statin dose per NICE NG238, expected to reduce LDL cholesterol by 40 per cent or more. Used when the 10 mg starting dose has not achieved the target LDL reduction.

Rosuvastatin 40 mg Tablets: The maximum dose, used only in patients whose LDL cholesterol has not been adequately controlled at 20 mg. The SmPC specifies that the 40 mg dose should only be prescribed under specialist supervision. All dose decisions are made by your prescriber.

Like all statins, rosuvastatin can cause side effects.

Common Side Effects (may affect up to 1 in 10 people):

• Muscle aches, pains, or weakness (myalgia). Contact your prescriber promptly if you experience unexplained muscle pain, particularly if severe or accompanied by dark urine.
• Headache.
• Gastrointestinal effects including abdominal pain, nausea, constipation, and diarrhoea.
• Dizziness.

Uncommon Side Effects (may affect up to 1 in 100 people):

• Raised liver enzymes on blood tests, usually asymptomatic.
• Raised creatine kinase, a marker of muscle involvement.
• Proteinuria (protein in the urine), monitored particularly at the 40 mg dose.
• A small increase in the risk of type 2 diabetes, associated with the statin class.

Serious Side Effects — Seek Urgent Medical Attention: Go to your nearest accident and emergency department or call 999 immediately if you experience severe muscle pain, weakness, or cramps, particularly with dark, tea coloured urine (rhabdomyolysis, risk higher at the 40 mg dose); signs of significant liver problems such as yellowing of the skin or eyes, severe abdominal pain, or very dark urine; or signs of a severe allergic reaction such as sudden swelling of the face, lips, tongue, or throat.

Rosuvastatin tablets may be suitable if:

• You are an adult with primary hypercholesterolaemia, mixed dyslipidaemia, or familial hypercholesterolaemia requiring LDL reduction.
• You have elevated cardiovascular risk and your prescriber has recommended statin therapy for prevention of cardiovascular events.
• You have homozygous familial hypercholesterolaemia under specialist supervision.
• You are already prescribed rosuvastatin and require a repeat prescription through an online prescribing service.

Rosuvastatin tablets are not suitable or require dose adjustment if:

• You are of Asian ancestry (e.g. Chinese, Japanese, Korean, Vietnamese, Filipino, and Indian). Increased plasma concentrations of rosuvastatin have been observed in these populations, so the recommended starting dose is 5 mg. The 40 mg dose is generally contraindicated or not recommended, and doses above 20 mg should be used with caution depending on the product SmPC and clinical judgement.
• You are pregnant or planning to become pregnant. Rosuvastatin is contraindicated in pregnancy.
• You are breastfeeding.
• You have active liver disease or persistently elevated liver enzymes of unknown cause.
• You have severe kidney impairment. Rosuvastatin 40 mg is contraindicated in severe kidney impairment.
• You have severe liver impairment.
• You have myopathy or risk factors for myopathy.
• You have a known allergy or hypersensitivity to rosuvastatin or any excipient listed in the SmPC.

Important Drug Interactions: Ciclosporin significantly increases rosuvastatin blood levels via OATP transporter inhibition — contraindicated or dose-limited per SmPC. Gemfibrozil is contraindicated, causing up to a sevenfold increase in rosuvastatin levels. Certain HIV antivirals (lopinavir/ritonavir, atazanavir/ritonavir) significantly increase rosuvastatin levels — dose limitation or avoidance required. Warfarin's anticoagulant effect may be modestly enhanced — INR monitoring advisable. Antacids (aluminium and magnesium hydroxide) reduce absorption — take rosuvastatin at least two hours before. Fibrates other than gemfibrozil increase myopathy risk.

Rosuvastatin is a Prescription Only Medicine. The clinical consultation is the essential first step. A prescription will only be issued if a registered prescriber concludes, based on their individual assessment of your circumstances, that rosuvastatin is clinically appropriate for you.

During your online consultation with Pharmacy Planet, a registered prescriber will review your cholesterol and lipid levels, cardiovascular risk assessment, ethnic background (relevant to starting dose per the SmPC), current medicines, kidney and liver function where available, and other relevant medical history. The prescriber will determine the appropriate strength and confirm that the 40 mg dose restriction does not apply inappropriately to your situation.

Not all consultations will result in a prescription. The prescriber may request blood test results, recommend a different statin, or advise that a full cardiovascular risk assessment by your GP is needed before proceeding.