HMG-CoA reductase inhibitors (statins)
Updated · Methodology
First line
Prescribed for primary prevention in patients with elevated cardiovascular risk. Dose 20–40 mg in the evening. The 80 mg dose is no longer recommended – restricted it in 2011 due to increased myopathy and rhabdomyolysis risk. New patients do not start at 80 mg; it is retained only for those who have taken it for over 12 months without adverse effects.
Sources
ICD-10: E78.5 · ICD-11: 5C80
First line
Simvastatin demonstrated efficacy in landmark RCTs – 4S (30% reduction in all-cause mortality) and HPS (24% reduction in vascular events). These trials laid the evidence foundation for the entire statin class. In current practice, atorvastatin and rosuvastatin are preferred due to more potent reduction and fewer interactions. Simvastatin remains a reasonable choice at doses up to 40 mg.
Sources
ICD-10: I25 · ICD-11: BA5Z
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Simvastatin is a moderate-potency statin, one of the most prescribed statins worldwide. It is prescribed for hyperlipidemia and for primary/secondary CV prevention ( 2019). In healthy adults, simvastatin is occasionally prescribed for general vascular protection or anti-aging, citing older meta-analyses. In people without confirmed CV risk factors, clinical studies do not justify prophylactic use. Simvastatin interacts with CYP3A4 more strongly than other statins (combinations with clarithromycin, erythromycin, itraconazole, and large amounts of grapefruit juice are prohibited due to rhabdomyolysis risk). In 2011 the limited the maximum simvastatin dose to 40 mg/day due to dose-dependent muscle toxicity risk. If simvastatin was prescribed at normal lipid levels, consider seeking a second opinion.
A prodrug – converted in the liver to an active β-hydroxy acid metabolite that competitively inhibits HMG-CoA reductase. Reduces hepatic cholesterol synthesis, upregulates receptors, and increases LDL clearance from plasma. Metabolized by CYP3A4 – considerably more sensitive to CYP3A4 inhibitors than atorvastatin. The restricted the 80 mg dose in 2011 due to elevated myopathy risk. Maximum dose is 20 mg with amlodipine and ranolazine, and 20 mg with amiodarone/verapamil/diltiazem; combination with azoles/macrolides/cyclosporine/gemfibrozil is contraindicated.
AEMPS summary of product characteristics (section 4.6): simvastatin is contraindicated in pregnancy; its safety in pregnant women has not been established and no controlled clinical studies have been done. Congenital anomalies after intrauterine exposure to HMG-CoA reductase inhibitors have been reported rarely, but in an analysis of about 200 prospectively followed pregnancies exposed in the first trimester to simvastatin or a closely related HMG-CoA reductase inhibitor, the rate of anomalies was comparable to that in the general population, a number large enough to exclude an increase of 2.5-fold or more. Maternal simvastatin may lower fetal levels of mevalonate, a precursor of cholesterol synthesis, while stopping lipid-lowering drugs during pregnancy should usually have little effect on the long-term risk of primary hypercholesterolaemia. Simvastatin is not used in women who are pregnant, trying to conceive or suspect they are pregnant, and treatment is stopped for the whole pregnancy or until pregnancy has been ruled out.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Grapefruit juice blocks CYP3A4 in the gut wall, and far more simvastatin reaches the blood. According to the Zocor SmPC, more than a litre of juice a day raised simvastatin acid exposure 7-fold. A single 240 ml glass in the morning with an evening dose raised it 1.9-fold, so spacing the two apart does not help. Excess statin damages muscle: pain and weakness in the thighs and shoulders, dark urine, raised creatine kinase. The SmPC says to avoid grapefruit juice throughout treatment. Pravastatin, rosuvastatin, fluvastatin and pitavastatin barely depend on this enzyme.
Source: AEMPS: Ficha técnica de Zocor 20 mg comprimidos recubiertos con película (simvastatina) (2026)
26 pairs found. Sorted from critical to minor.
Mechanism
Atazanavir inhibits CYP3A4. Simvastatin rises 10+ fold – fatal rhabdomyolysis.
Symptoms
Myalgia, dark urine within 5-10 days.
Management
Combination contraindicated. Switch to pravastatin or rosuvastatin.
Sources
Mechanism
Cyclosporine blocks two simvastatin clearance routes: the OATP1B1 transporter (uptake into hepatocytes) and CYP3A4. Active simvastatin levels rise 5- to 8-fold. The Zocor label specifically lists cyclosporine as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
The combination is not prescribed. For transplant patients needing a statin, use pravastatin up to 20 mg/day or fluvastatin (minimal interaction with cyclosporine). Check creatine kinase every 4–6 weeks.
Sources
Mechanism
Simvastatin clearance is 98% dependent on hepatic CYP3A4. Clarithromycin is a potent inhibitor of this enzyme; simvastatin plasma concentrations rise 10-fold or more. The lists this combination as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups, dark urine, elevated creatine kinase on lab work. Severe cases progress to rhabdomyolysis with acute kidney injury. First signs appear within 3–7 days of concurrent dosing.
Management
The combination is not prescribed. Hold simvastatin for the duration of clarithromycin therapy or switch the patient to pravastatin or rosuvastatin – these statins use a different metabolic pathway and do not interact. If simvastatin cannot be paused, replace the antibiotic: azithromycin or a non-macrolide class based on susceptibility.
Sources
Mechanism
Cobicistat is a strong CYP3A4 inhibitor. Simvastatin rises 30-fold with fatal rhabdomyolysis risk. Tybost Section 4.3.
Symptoms
Myalgia, weakness, dark urine within 5 days.
Management
Combination contraindicated. Alternative statin: pravastatin 20–40 mg or rosuvastatin 5–10 mg.
Sources
Mechanism
Darunavir inhibits CYP3A4. Simvastatin rises 10+ fold – fatal rhabdomyolysis.
Symptoms
Myalgia, CK above 50× ULN.
Management
Combination contraindicated. Pravastatin or rosuvastatin.
Sources
Mechanism
Erythromycin inhibits CYP3A4. Simvastatin is a sensitive substrate; its concentration rises 6-fold. High rate of rhabdomyolysis with fatal cases reported. Zocor Section 4.3 – strict contraindication.
Symptoms
Muscle pain, weakness, dark urine within 7 days. Labs show sharp rise in creatine kinase and creatinine.
Management
Combination contraindicated. Hold simvastatin during erythromycin therapy. Alternative: pravastatin or rosuvastatin – neither is metabolised via CYP3A4.
Sources
Mechanism
Simvastatin enters the liver through the OATP1B1 transporter, which gemfibrozil blocks. Statin concentrations in muscle rise, and the fibrate's own myotoxic effect adds to that. The label states it plainly: in patients with an unsatisfactory lipid response to either drug alone, the benefit of combined therapy does not outweigh the risks of severe myopathy, rhabdomyolysis and acute renal failure.
Symptoms
Muscle pain and weakness, most often in the thighs and shoulders, with tenderness on pressure. Then dark tea-coloured urine, a sharp rise in creatine kinase and myoglobinuria. In a proportion of cases acute renal failure develops and ends fatally.
Management
The label prohibits this combination. When both triglyceride lowering and a statin are needed, gemfibrozil is switched to fenofibrate, which does not block OATP1B1 to the same degree and is not prohibited with simvastatin. The 2019 guidelines hold the same line: gemfibrozil is not combined with statins.
Sources
Mechanism
Itraconazole is the strongest CYP3A4 inhibitor in clinical use. Simvastatin is a sensitive substrate; its concentration rises 10–20 fold. Risk of rhabdomyolysis with acute kidney injury is the highest among statin–azole combinations.
Symptoms
Rhabdomyolysis within 3–7 days: myalgia, weakness, dark urine. CK above 50× ULN, oliguria.
Management
Combination contraindicated. Stop simvastatin one week before starting itraconazole and resume 2 weeks after the last dose. Alternative: pravastatin or rosuvastatin.
Sources
Mechanism
Simvastatin clearance is 98% via hepatic CYP3A4. Ketoconazole is one of the strongest CYP3A4 inhibitors. Simvastatin plasma levels rise 10-fold or more. The lists the combination as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
The combination is not prescribed. Hold simvastatin during ketoconazole therapy or switch to pravastatin or rosuvastatin (no CYP3A4 use). Alternative antifungals: terbinafine or echinocandins.
Sources
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Simvastatin rises 10+ fold, rhabdomyolysis risk. Noxafil Section 4.3.
Symptoms
Rhabdomyolysis within 5–10 days.
Management
Combination contraindicated. Pravastatin or rosuvastatin.
Sources
Mechanism
Simvastatin is cleared via hepatic CYP3A4. Ritonavir is the strongest available CYP3A4 inhibitor. Simvastatin plasma levels rise 30-fold or more. The lists the combination as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
The combination is not prescribed. For HIV patients on ritonavir-boosted therapy who need a statin, use low-dose pravastatin or rosuvastatin. Cap rosuvastatin at 10 mg/day with ritonavir.
Sources
Mechanism
Amiodarone inhibits CYP3A4, the enzyme that metabolises simvastatin. In a study cited in the US simvastatin label (), amiodarone 400 mg a day raised the AUC of simvastatin and its active acid form about 1.75-fold. Higher levels raise the risk of myopathy and rhabdomyolysis: in a clinical study, myopathy occurred in 6% of patients taking simvastatin 80 mg with amiodarone (simvastatin SmPC).
Symptoms
Muscle pain, tenderness or weakness with creatine kinase (CK) above 10 times the upper limit of normal. In rhabdomyolysis, urine turns dark from myoglobin and acute kidney injury may follow.
Management
The combination is not contraindicated, but the simvastatin dose is capped: no more than 20 mg a day, and higher doses with amiodarone are avoided (simvastatin SmPC). The US simvastatin and amiodarone labels () set the same limit. The amiodarone SmPC recommends a statin that is not metabolised by CYP3A4 during co-administration. Warn the patient about myopathy and ask them to report unexplained muscle pain, tenderness or weakness promptly (simvastatin SmPC).
Sources
Mechanism
Amlodipine moderately inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise by about 77%. Rhabdomyolysis has been reported at simvastatin doses of 40 mg or above.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap simvastatin at 20 mg/day when combined with amlodipine. If targets are missed, switch to pravastatin or rosuvastatin (no CYP3A4 dependence) or replace amlodipine with lisinopril or telmisartan.
Sources
Mechanism
Carbamazepine induces CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels fall 5- to 10-fold; lipid-lowering effect drops proportionally.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During carbamazepine therapy, increase simvastatin 2- to 3-fold with lipid profile and creatine kinase monitoring, or switch to pravastatin/rosuvastatin (metabolism less CYP3A4-dependent). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Sources
Mechanism
Diltiazem inhibits CYP3A4. Simvastatin concentration rises 2.7-fold. Zocor Section 7 caps simvastatin at 10 mg/day with diltiazem due to myopathy and rhabdomyolysis risk.
Symptoms
Pain in thighs and shoulder girdle, CK above 5× ULN, dark urine.
Management
Cap simvastatin at 10 mg/day. Alternative: pravastatin 40 mg or rosuvastatin 10–20 mg with comparable effect.
Sources
Mechanism
Dronedarone inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise 4-fold. Zocor 2012 caps simvastatin at 10 mg/day with dronedarone.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap simvastatin at 10 mg/day when combined. If targets are missed, switch to pravastatin or rosuvastatin (no CYP3A4 dependence).
Sources
Mechanism
Efavirenz induces CYP3A4. Simvastatin falls 60% – lipid-lowering effect lost.
Symptoms
returns to baseline.
Management
Alternative statin – pravastatin or rosuvastatin.
Mechanism
Fluconazole at 200 mg/day or above moderately inhibits CYP3A4 – the main simvastatin metabolic route. Simvastatin plasma levels rise 2- to 3-fold, with increased myopathy risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
For short fluconazole courses (up to 7 days), hold simvastatin or halve the dose. For prolonged systemic therapy, switch to pravastatin/rosuvastatin or use an alternative antifungal (echinocandins).
Sources
Mechanism
Phenytoin induces CYP3A4. Simvastatin level falls 60%, lipid-lowering effect is lost. cholesterol returns to baseline, cardiovascular risk rises.
Symptoms
returns to baseline over 4–6 weeks.
Management
Alternative statin: pravastatin or rosuvastatin (not CYP3A4-metabolised). Alternative anticonvulsant: levetiracetam.
Mechanism
Rifampicin strongly induces CYP3A4 and the OATP1B1 transporter – the routes of simvastatin activation and hepatocyte uptake. Simvastatin plasma levels fall by 87%; lipid-lowering effect practically disappears.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During anti-TB therapy, switch simvastatin to pravastatin (less induction-sensitive metabolism). Induction persists for 2 weeks after rifampicin stops – reintroduce simvastatin gradually.
Sources
Mechanism
Ticagrelor inhibits P-glycoprotein. Simvastatin rises 1.5-fold. Brilinta caps simvastatin at 40 mg/day.
Symptoms
Myalgia, rising CK.
Management
Cap simvastatin at 40 mg/day.
Sources
Mechanism
Verapamil inhibits CYP3A4 and P-glycoprotein. Simvastatin rises 2–3 fold with myopathy and rhabdomyolysis risk. Zocor Section 7 caps simvastatin at 10 mg/day with verapamil.
Symptoms
Myalgia, weakness, rising CK within 1–3 weeks.
Management
Cap simvastatin at 10 mg/day. Alternative: pravastatin or rosuvastatin.
Sources
Mechanism
Dual statin therapy – additive myopathy and rhabdomyolysis risk. Simvastatin additionally depends on CYP3A4 (by 98%), amplifying risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
The combination is not prescribed. Use one statin titrated to target. If insufficient, add ezetimibe.
Mechanism
Simvastatin is broken down by the CYP3A4 enzyme. Strong inhibitors of this enzyme, including erythromycin and clarithromycin, raise the risk of myopathy and rhabdomyolysis and are contraindicated with simvastatin (simvastatin SmPC). Azithromycin is not on this list: it is a weak inhibitor of cytochrome P450 enzymes, although inhibition of CYP3A4 cannot be fully ruled out (azithromycin SmPC). There are no data on higher simvastatin levels with azithromycin, but post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC).
Symptoms
Muscle pain, weakness, cramps or tenderness, sometimes with malaise and fever. In rhabdomyolysis, urine turns dark from myoglobin and there is a risk of acute kidney injury (statin SmPCs).
Management
Use the combination with caution: post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC). Azithromycin is not among the strong CYP3A4 inhibitors that are contraindicated with simvastatin (simvastatin SmPC). Warn patients who start simvastatin or raise its dose about the risk of myopathy and ask them to report unexplained muscle pain, tenderness or weakness at once. If these occur, measure creatine kinase (CK): stop simvastatin if CK is above 5 times the upper limit of normal (simvastatin SmPC).
Sources
Mechanism
Both drugs can damage muscle on their own: simvastatin causes myopathy and rhabdomyolysis (simvastatin SmPC), and colchicine taken long term at therapeutic doses causes neuromuscular toxicity and rhabdomyolysis (colchicine SmPC). Together the risk of myopathy rises: adding one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis, including a fatal case (US colchicine label, ). The interaction may be pharmacokinetic, pharmacodynamic or both (US colchicine label). Such cases with this combination have also been reported in patients with renal impairment (simvastatin SmPC).
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. The risk is higher in older patients and in renal impairment.
Management
Before combining, weigh the benefit against the increased risk of myopathy and rhabdomyolysis (US simvastatin and colchicine labels, ). If it is used, monitor for muscle pain, tenderness and weakness, especially at the start of treatment and when the dose of either drug is increased (US simvastatin label); creatine kinase monitoring will not necessarily prevent severe myopathy (US colchicine label). Monitor patients with renal impairment closely (simvastatin SmPC). Adjust the colchicine dose to age and renal function: in older patients and in renal impairment the total dose over a 4-day gout attack should not exceed 3 mg, in moderate renal impairment the dose may need to be halved, and in severe renal impairment colchicine is contraindicated (colchicine SmPC). If muscle toxicity appears, interrupt or stop colchicine (US colchicine label); symptoms usually resolve within one week to several months after stopping (colchicine SmPC).
Sources
Mechanism
Simvastatin weakly inhibits CYP3A4 and partly displaces warfarin from protein binding. INR may rise by 0.5–1 in the first 2 weeks.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
On simvastatin initiation, check INR at 1 and 2 weeks, then per usual schedule. If INR rises, reduce warfarin by 10%. Alternatives: pravastatin or rosuvastatin (minimal warfarin effect).
Sources
Verbatim lines from the interaction sections, in the language of the label
«-Administración concomitante de gemfibrozilo, ciclosporina o danazol (ver secciones 4.4 y 4.5)»AEMPS, section 4.3 · Open on CIMA
«telaprevir, eritromicina, claritromicina, telitromicina y nefazodona y medicamentos que contienen cobicistat ) (ver secciones 4.4 y 4.5).»AEMPS, section 4.3 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole)…»FDA, section 7 · Open on DailyMed
«telaprevir, eritromicina, claritromicina, telitromicina y nefazodona y medicamentos que contienen cobicistat ) (ver secciones 4.4 y 4.5).»AEMPS, section 4.3 · Open on CIMA
«telaprevir, eritromicina, claritromicina, telitromicina y nefazodona y medicamentos que contienen cobicistat ) (ver secciones 4.4 y 4.5).»AEMPS, section 4.3 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole)…»FDA, section 7 · Open on DailyMed
«-Administración concomitante de gemfibrozilo, ciclosporina o danazol (ver secciones 4.4 y 4.5)»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Concomitant use of cyclosporine, danazol or gemfibrozil [see DRUG INTERACTIONS ( 7.1 )].»FDA, section 4 · Open on DailyMed
«aumentan el AUC aproximadamente 5 veces o más) (p. ej., itraconazol, ketoconazol,»AEMPS, section 4.3 · Open on CIMA
«aumentan el AUC aproximadamente 5 veces o más) (p. ej., itraconazol, ketoconazol,»AEMPS, section 4.3 · Open on CIMA
«posaconazol, voriconazol, inhibidores de la proteasa del VIH (p. ej. nelfinavir), boceprevir,»AEMPS, section 4.3 · Open on CIMA
«posaconazol, voriconazol, inhibidores de la proteasa del VIH (p. ej. nelfinavir), boceprevir,»AEMPS, section 4.3 · Open on CIMA
«El riesgo de miopatía y rabdomiólisis aumenta con la administración concomitante de amiodarona con simvastatina (ver sección 4.4). En un estudio clínico, se comunicó miopatía en el 6 % de los…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed simvastatin 10 mg…»FDA, section 7 · Open on DailyMed
«Amlodipino: Los pacientes en tratamiento con amlodipino, tratados concomitantemente con simvastatina, tienen un riesgo mayor de miopatía. En un estudio farmacocinético, la administración concomitante…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed simvastatin 10 mg…»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see DRUG INTERACTIONS ( 7.1 )].»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see DRUG INTERACTIONS ( 7.1 )].»FDA, section 4 · Open on DailyMed
«Se debe considerar suspender temporalmente el tratamiento con simvastatina en pacientes que toman daptomicina a menos que los beneficios de la administración conjunta superen el riesgo (ver sección…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Intervention: If treatment with daptomycin is required, consider temporarily suspending simvastatin during…»FDA, section 7 · Open on DailyMed
«claritromicina, telitromicina, nefazodona y medicamentos que contienen cobicistat, así como con gemfibrozilo, ciclosporina y danazol (ver sección 4.3). Si el tratamiento con inhibidores potentes de…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin: Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed simvastatin 10 mg…»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: Lipid-Modifying Agents: Lomitapide, lovastatin, simvastatin»FDA, section 4 · Open on DailyMed
«Claritromicina no se debe usar concomitantemente con los inhibidores de la HMG-CoA reductasa (estatinas) que son ampliamente metabolizados por la CYP3A4 (lovastatina o simvastatina), debido al…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Lomitapide, lovastatin, and simvastatin (4.5)»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Lipid-modifying Agents: lomitapide, lovastatin, simvastatin»FDA, section 4 · Open on DailyMed
«INHIBIDORES DE LA HMG CO-A REDUCTASA: El aumento de las concentraciones plasmáticas de lovastatina o simvastatina puede provocar miopatía e incluso rabdomiólisis. Por tanto, está contraindicada la…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Anti-gout: colchicine, in patients with renal and/FDA, section 4 · Open on DailyMed
«Tratamiento simultáneo con astemizol, terfenadina, disopiramida, cisaprida, pimocida, alcaloides del cornezuelo (como la ergotamina y la dihidroergotamina), simvastatina, atorvastatina o lovastatina.»AEMPS, section 4.3 · Open on CIMA
«Uso concomitante de repaglinida, dasabuvir, selexipag (ver sección 4.5) simvastatina o rosuvastatina 40 mg (ver secciones 4.4 y 4.5).»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Combination therapy of gemfibrozil with simvastatin (see WARNINGS and PRECAUTIONS ).»FDA, section 4 · Open on DailyMed
«Drug Interactions: Additionally, the following other drugs are contraindicated with ketoconazole tablets: methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine…»FDA, section 4 · Open on DailyMed
«Inhibidores de la HMG-CoA reductasa p.ej., simvastatina, lovastatina, ya que el incremento de las concentraciones plasmáticas de estos fármacos puede producir rabdomiolisis.»AEMPS, section 4.3 · Open on CIMA
«Administración concomitante con los inhibidores de la HMG-CoA reductasa simvastatina, lovastatina y atorvastatina (ver sección 4.5).»AEMPS, section 4.3 · Open on CIMA
«HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: Coadministration with the HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin…»FDA, section 4 · Open on DailyMed
«Inhibidores de la HMG Co-reductasa: Los inhibidores de la HMG-Co-reductasa, como lovastatina y simvastatina, son altamente dependientes del metabolismo por CYP3A, se espera que presenten un marcado…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: HMG-CoA Reductase Inhibitors: lovastatin, simvastatin»FDA, section 4 · Open on DailyMed
«DRUG INTERACTIONS: HMG-CoA Reductase Inhibitors simvastatin, lovastatin, atorvastatin Increased plasma concentration of HMGCoA reductase inhibitor. Limit the dose of lovastatin to 40 mg. Limit the…»FDA, section 7 · Open on DailyMed
«7.2. Impact of Amlodipine on Other Drugs: Simvastatin Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on…»FDA, section 7 · Open on DailyMed
«Drug Interactions: In a healthy volunteer crossover study (N=10), coadministration of a single 20 mg dose of simvastatin at the end of a 14-day regimen with 120 mg BID diltiazem SR resulted in a…»FDA, section 7 · Open on DailyMed
Showing 40 of 104, heaviest first
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Simvastatin is evaluated for the following indications with varying evidence strength: Established ASCVD, secondary prevention (evidence tier A), Dyslipidemia, primary CV prevention (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Simvastatin (≥ 1 in 100): Myalgia, Headache, Dyspepsia, nausea, constipation, Transaminase elevation (usually transient). See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): simvastatin is contraindicated in pregnancy; its safety in pregnant women has not been established and no controlled clinical studies have been done. Congenital anomalies after intrauterine exposure to HMG-CoA reductase inhibitors have been reported rarely, but in an analysis of about 200 prospectively followed pregnancies exposed in the first trimester to simvastatin or a closely related HMG-CoA reductase inhibitor, the rate of anomalies was comparable to that in the general population, a number large enough to exclude an increase of 2.5-fold or more. Maternal simvastatin may lower fetal levels of mevalonate, a precursor of cholesterol synthesis, while stopping lipid-lowering drugs during pregnancy should usually have little effect on the long-term risk of primary hypercholesterolaemia. Simvastatin is not used in women who are pregnant, trying to conceive or suspect they are pregnant, and treatment is stopped for the whole pregnancy or until pregnancy has been ruled out.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
Simvastatin is contraindicated in: Active liver disease or unexplained persistent transaminase elevation; Concurrent potent CYP3A4 inhibitors – itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors; Concurrent gemfibrozil, cyclosporine, or danazol. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Simvastatin + Ezetimibe, Atorvastatin, Atorvastatin + Ezetimibe, Cod liver oil, Fluvastatin, Lovastatin, Pravastatin, Ezetimibe