Simvastatin
Risk Factor: XM
Class: ANTILIPEMIC AGENTS
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Simvastatin is used to lower elevated levels of cholesterol. It has the same cholesterol-lowering mechanism (i.e., inhibition of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase) as some other agents in this class (e.g., see Fluvastatin, Lovastatin, and Pravastatin) and is structurally similar to lovastatin and pravastatin.
Simvastatin was not teratogenic in rats and rabbits at doses up to 3 times the human exposure based on body surface area (1). A decrease in fertility was observed in male rats dosed for 34 weeks at 4 times the maximum human exposure level based on area under the concentration curve (AUC), but this effect was not observed when the study was repeated for 11 weeks (1). Male dogs given 10 mg/kg/day (about 2 times the human exposure based on AUC at 80 mg/day) demonstrated a drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration, and giant cell formation (1).
Shepard reviewed four studies involving the administration of simvastatin to pregnant rats and rabbits (2,3,4 and 5). Although maternal weight was reduced compared with controls, no teratogenicity, adverse effects on fertility, or interference with postnatal behavior or fertility were observed.
Five cases of fetal loss were reported to the FDA in 1995, but additional data on these cases are not available (F. Rosa, personal communication, FDA, 1995).
A 1996 report described the outcomes of simvastatin-exposed pregnancies gathered from a worldwide postmarketing surveillance by the manufacturer (6). A total of 187 cases of inadvertent exposure to simvastatin had been identified, among which the outcomes of 15 (8%) were still pending, 46 (25%) had been lost to follow-up, and 40 (21%) underwent elective abortions. None of the products of conception from the elective abortions underwent morphologic and/or chromosomal evaluations (7). In the remaining 86 cases, there were 64 (74.4%) normal outcomes, 13 (15.1%) spontaneous abortions, 5 (5.8%) congenital malformations, 1 (1.2%) fetal death, and 3 (3.5%) miscellaneous adverse outcomes. In at least 59 (92%) of the 64 normal outcomes, the mother had been taking the drug before conception so that exposure had occurred from the start of the pregnancy. In three cases, exposure occurred from the 10th week through term, and in two cases the mother took the drug during the 1st trimester, but the exact timing during this period was unknown. The one fetal death occurred at 23 weeks' gestation in a pregnancy exposed to simvastatin (10 mg/day) during the first 34 weeks of gestation, but specific details on the case were not available. Congenital anomalies after 1st-trimester exposure to simvastatin occurred in five infants, one of which was a twin. Four reports were prospective and one was retrospective. The defects were (maternal dose and exposure in weeks from last menstrual period): polydactyly with small, boneless, outgrowth from hand (10 mg/day, 35 weeks); unilateral cleft lip without cleft palate, amniocentesis normal (10 mg/day, 06 weeks); balanic hypospadias (10 mg/day, 06 weeks); trisomy 18, multiple malformations in a dead fetus, other twin normal (5 mg/day, 07 weeks); and club foot, mother also treated for hypertension (10 mg/day, 012 weeks). The cases of polydactyly and hypospadias were thought not to be drug induced because the time of drug exposure in both cases occurred before the critical periods for these defects (6). The trisomy was also dismissed as drug induced because of the lack of evidence that this defect could be caused by drugs. The miscellaneous adverse effects were patent ductus arteriosus in a 1814-g premature infant delivered from a hypertensive mother (10 mg/day, 010 weeks); respiratory distress, cardiac arrhythmia, anemia, and infection in a 1900-g premature infant delivered from a hypertensive mother (10 mg/day, 07 weeks); and bilateral hydrocele, hyperbilirubinemia in a 1720-g premature infant (20 mg/day, 09 weeks). All three cases were thought to be possibly related to prematurity (6).
In summary, based on the animal data and limited human experience, exposure to simvastatin during early pregnancy does not appear to present a significant risk to the fetus. The outcomes reported above are within those expected in a nonexposed population. However, because the interruption of cholesterol-lowering therapy during pregnancy should have no apparent effect on the long-term treatment of hyperlipidemia, simvastatin should not be used during pregnancy. Women taking this agent before conception should ideally stop the therapy before becoming pregnant and certainly on recognition of pregnancy. Accidental use of the drug during gestation, though, apparently has no known consequences for the fetus.
Breast Feeding Summary
No published reports describing the use of simvastatin during lactation have been located, and it is not known whether the agent is excreted into milk. However, the passage of simvastatin into milk should be expected because at least two other similar agents (Fluvastatin and Pravastatin) appear in human milk. Because of the potential for adverse effects in the nursing infant, the drug should not be used during lactation.
References
- Product information. Zocor. Merck, 2000.
- Wise LD, Minsker DH, Robertson RT, Bokelman DL, Akutsu S, Fujii T. Simvastatin (mk-0733): oral fertility study in rats. Oyo Yakuri 1990;39:12741. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:35960.
- Wise LD, Majka JA, Robertson RT, Bokelman DL. Simvastatin (mk-0733): oral teratogenicity study in rats pre- and postnatal observation. Oyo Yakuri 1990;39:14358. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:35960.
- Wise LD, Prahalada S, Robertson RT, Bokelman DL, Akutsu S, Fujii T. Simvastatin (mk-0733): oral teratogenicity study in rabbits. Oyo Yakuri 1990;39:15967. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:35960.
- Minsker DH, Robertson RT, Bokelman DL. Simvastatin (mk-0733): oral late gestation and lactation study in rats. Oyo Yakuri 1990;39:16979. As cited in Shepard TH. Catalog of Teratogenic Agents. 7th ed. Baltimore, MD: Johns Hopkins University Press, 1992:35960.
- Manson JM, Freyssinges C, Ducrocq MB, Stephenson WP. Postmarketing surveillance of lovastatin and simvastatin exposure during pregnancy. Reprod Toxicol 1996;10:43946.
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Manson JM. Postmarketing surveillance of lovastatin and simvastatin exposure during pregnancy. Reprod Toxicol 1997;11:6412.
Questions and Answers
Is it ok to take atenolol 50 mg daily at the same time taking simvastatin 40 mg daily to lower cholesterol?, Is it ok to take atenolol 50 mg daily at the same time taking simvastatin 40 mg daily to lower cholesterol?
i have been on both for more than six years now and no problems in fact a recent uk study has found that statins given to healthy people may prevent heart attacks and strokes your body needs both so keep taking them
what is the difference between simvastatin and pravastatin?, One of these genereic cholesterol lowering medicines is available at Walmart for $4.00 and the other is not.
Both medications are in the same drug class and work by the same mechanism to lower cholesterol. However, simvastatin has a greater effect on lowering LDL (bad cholesterol) and triglycerides and increasing HDL (good cholesterol) than pravastatin. Simvastatin is also more likely to cause the rare but serious side effect of rhabdomyolysis because it is primarily eliminated by the liver where as pravastatin is excreted in the urine. You and your doctor will have to decide if the effects of pravastatin are enough based on how high your cholesterol is and any other health conditions you have.
do anyone know the difference between simvastatin and otarvastatin?, simvastatin makes me feel good but i thought that maybe it stops me from sleeping?is it possible?
Both are synthetic lipid-lowering agents. Though similar drugs, they have different components.
As for sleeping problems with simvastatin, studies show that there's an increase in incidence of insomia in simvastatin users.
What time of day should I take Simvastatin?, I read that Simvaststin should be taken at night because the body produces more cholesterol then. I work nights and sleep during the day. I assume I should take it in the morning before I go to bed.
Is that a safe assumption? Does it really matter when I take it?
I was prescribed 20 mgs for high cholesterol. My pharmacist told me to take at night because that's when the most cholesterol is produced.
My sister works nights so I'm very familiar with that type of schedule. Assuming you wake up about 10 pm-ish, you should take it about that time.
Side effects of Simvastatin? Is there a website where ordinary people give their experiences? ?, My father has dementia and while he was in hospital they doubled the dose of Simvastatin. His behaviour has deteriorated, and he has become very aggressive. Anyone else experienced this? I'd really appreciate some comments. Thanks
I took it to control cholesterol - for which it is very effective. It had no effect on my behaviour, but I did suffer from severe cramps and muscle aches, so I came off it.
Is anyone taking Simvastatin and having side effects? It is the generic form of Evista for cholesterol. ?, I am very sore in the lower back and stomach and it hurts to breathe. I am wondering if it is from this pill.
Yes- I have taken Simvastatin daily and regularly for 4 years for my cardiac and Cholesterol problems. I too have noticed back pain, body pain and pain in the leg joints. On reporting this he has changed the medication and given Storvas - another Vastatin group (Atovastin Calcium tablets) medicine but the problem continues.
If you have more of the pain it is better you consult your doctor and let him give some alternate medication. However please note the side effects of Simvastatin as under and report if it is severe.
Side effects that you should report to your doctor or health care professional as soon as possible:
• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• dark urine
• fever
• joint pain
• muscle cramps, pain
• redness, blistering, peeling or loosening of the skin, including inside the mouth
• trouble passing urine or change in the amount of urine
• unusually weak or tired
• yellowing of the eyes or skin
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
• constipation
• heartburn
• stomach gas, pain, upset -
Why the statins (simvastatin and other lypodecreasing drugs) are prescribed to be taken before bed time?, I mean why is it better to take statins before bedtime (at evening) than at morning. F.e. the h2-blockers are taken at evening because more hystamin is secreted at night so the effect of the drug will be better. So what effect of the statins will be better if they r taken at night?
The reason that the earlier available statins were recommended for use at night was because they had relatively short half lives, and bedtime administration worked best because in most people cholesterol biosynthesis takes place in the early morning hours.
However that is not the case with Lipitor, Crestor or Pravachol, since they have half lives of 19-22 hours and therefore morning admiistration would be more suitable.
Simvastatin. How long before I get used to them?, I've been on Simvastatin now for about 2 months. I've lost a stone and am still sick regularly and feel rotten. Have spoken to the doctor and he says it'll take time. But how much?
I came off mine after about four months - that was back in June, and I still feel lousy! Simvastatin is nasty stuff. I can only give you the same advice I was given by friends with medical training and an inside knowlege of the health service - be assertive with your doctor and don't be fobbed off!
