Formulary
Simvastatin: Indications, Dosing, Side Effects and Interactions
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the liver.
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Simvastatin: Indications, Dosing, Side Effects and Interactions
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the liver.
Drug action
Statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the liver.
Indications and dose
**Primary hypercholesterolaemia, or combined (mixed) hyperlipidaemia in patients who have not responded adequately to diet and other appropriate measures**
- **Adult** (By Mouth): 10-20 mg once daily, dose to be taken at night, then increased if necessary up to 80 mg once daily, dose to be taken at night, adjusted at intervals of at least 4 weeks; 80 mg dose only for those with severe hypercholesterolaemia and at high risk of cardiovascular complications.
**Homozygous familial hypercholesterolaemia in patients who have not responded adequately to diet and other appropriate measures**
- **Adult** (By Mouth): Initially 40 mg once daily, dose to be taken at night, then increased if necessary up to 80 mg once daily, dose to be taken at night, adjusted at intervals of at least 4 weeks; 80 mg dose only for those with severe hypercholesterolaemia and at high risk of cardiovascular complications.
**Prevention of cardiovascular events in patients with atherosclerotic cardiovascular disease or diabetes mellitus**
- **Adult** (By Mouth): Initially 20-40 mg once daily, dose to be taken at night, then increased if necessary up to 80 mg once daily, dose to be taken at night, adjusted at intervals of at least 4 weeks; 80 mg dose only for those with severe hypercholesterolaemia and at high risk of cardiovascular complications.
**Hyperlipidaemia including familial hypercholesterolaemia for simvastatin**
- **Child 5-9 years** (By mouth): Initially 10 mg once daily, dose to be taken at night, then increased if necessary up to 20 mg once daily, dose to be taken at night, increased at intervals of at least 4 weeks.
- **Child 10-17 years** (By mouth): Initially 10 mg once daily, dose to be taken at night, then increased if necessary up to 40 mg once daily, dose to be taken at night, increased at intervals of at least 4 weeks.
Cautions
Risk factors for muscle toxicity, including myopathy or rhabdomyolysis Cautions, further information Muscle effects Muscle toxicity can occur with all statins, however the likelihood increases with higher doses and in certain patients. Statins should be used with caution in patients at increased risk of muscle toxicity. This includes the elderly, those with a personal or family history of muscular disorders, history of muscular toxicity or unexplained persistent muscle pain, history of liver disease, a high alcohol intake, known genetic polymorphisms-consult product literature, renal impairment, hypothyroidism, or those who undertake strenuous exercise. M See also Monitoring requirements . Hypothyroidism Hypothyroidism should be managed adequately before starting treatment with a statin.
Side effects
Common or very common Arthralgia; asthenia; constipation; diarrhoea; dizziness; flatulence; gastrointestinal discomfort; headache; muscle complaints; nausea; sleep disorders; thrombocytopenia Uncommon Alopecia; hepatic disorders; memory loss; pancreatitis; paraesthesia; sexual dysfunction; skin reactions; vomiting Rare or very rare Lupus-like syndrome; myopathy; peripheral neuropathy; tendon disorders Frequency not known Depression; diabetes mellitus (in those at risk); interstitial lung disease; neuromuscular dysfunction Side-effects, further information Muscle effects Although myalgia has been reported commonly in patients receiving statins, muscle toxicity truly attributable to statin use is rare. The risk of myopathy, myositis, and rhabdomyolysis associated with statin use is also rare. If muscle pain, weakness, or cramps occur during treatment, creatine kinase concentrations should be measured; if the concentration is more than 5 times the ULN (in the absence of strenuous exercise), treatment should be discontinued. If muscular symptoms are severe and cause daily discomfort, treatment discontinuation should be considered, even if creatine kinase concentrations are less than 5 times the ULN. If symptoms resolve and creatine kinase concentrations return to normal, the statin can be reintroduced, or introduction of an alternative statin can be considered, at the lowest dose and the patient monitored closely. Diabetes Statins should not be discontinued if there is an increase in the blood-glucose concentration 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. Side-effects For simvastatin Rare or very rare Acute kidney injury; anaemia Frequency not known Cognitive impairment
Interactions
**Severe interactions:**
- In a different study, a renal transplant patient with severe renal impairment who was receiving ciclosporin and multiple other medications demonstrated a 12-fold greater exposure to total ezetimibe...
- No clinically significant pharmacokinetic interactions have been observed between ezetimibe and drugs known to be metabolised by cytochromes P450 1A2, 2D6, 2C8, 2C9, and 3A4, or N-acetyltransferase.
- Anticoagulants: Concomitant administration of ezetimibe (10 mg once daily) had no significant effect on bioavailability of warfarin and prothrombin time in a study of twelve healthy adult males.
- In patients taking coumarin anticoagulants, prothrombin time should be determined before starting INEGY and frequently enough during early therapy to ensure that no significant alteration of...
**Other interactions (60):**
- OATP1B) pathways may increase simvastatin and simvastatin acid plasma concentrations and may lead to an increased risk of myopathy/rhabdomyolysis.
- Consult the prescribing information of all concomitantly used drugs to obtain further information about their potential interactions with simvastatin and/or the potential for enzyme or transporter...
- Pharmacodynamic interactions Interactions with lipid-lowering medicinal products that can cause myopathy when given alone The risk of myopathy, including rhabdomyolysis, is increased during...
- Additionally, there is a pharmacokinetic interaction of simvastatin with gemfibrozil resulting in increased simvastatin plasma levels (see below Pharmacokinetic interactions and sections 4.3 and 4.4).
- Rare cases of myopathy/rhabdomyolysis have been associated with simvastatin co-administered with lipid-modifying doses ( 1 g/day) of niacin (see section 4.4).
- Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis.
Pregnancy
Statins should be avoided in pregnancy (discontinue 3 months before attempting to conceive) as congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development.
Breast feeding
Manufacturer advises avoid-no information available.
Hepatic impairment
In general, manufacturers advise caution (risk of increased exposure); avoid in active disease or unexplained persistent elevations in serum transaminases.
Renal impairment
Dose adjustments Doses above 10 mg daily should be used with caution if creatinine clearance less than 30 mL/minute, M see Prescribing in renal impairment .
Medicinal forms
Solution,Tablet,Suspension
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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