Compatibility of commonly used drugs in lactation
Amy Brown, Wendy Jones in A Guide to Supporting Breastfeeding for the Medical Profession, 2019
There is no research on the use of statins during breastfeeding. Cholesterol is important to the development of the baby and the long-term effects of lowered levels are unknown. Simvastatin – oral bioavailability 5%, PPB 95%, no studies. Atorvastatin – oral bioavailability 14%, PPB >98%, no studies. Pravastatin – oral bioavailability 17%, PPB 50%, no studies. Rosuvastatin – oral bioavailability 20%, PPB 88%, RID 0.6–0.77%. Study of one patient but baby was not breastfed so no outcome data.
Medications
Henry J. Woodford in Essential Geriatrics, 2022
The PROSPER study is the only large cholesterol trial with a mean age of 75 or over (n = 5,804; mean age 75 [range 70–82]; follow-up 3.2 years).60 It recruited people either with vascular disease (44%) or vascular risk factors (e.g. smoking, hypertension or diabetes) and compared pravastatin (40 mg) to placebo. Cognitive impairment (MMSE < 24) was one of the exclusion criteria. The primary endpoint, a composite of coronary heart death, non-fatal MI or any stroke, was reduced (HR 0.85; 95% CI 0.74–0.97; 14.1% v 16.2%; NNT 152 per year). However, significant benefit was limited to a reduction in coronary heart disease death or non-fatal myocardial infarction (HR 0.81, 95% CI 0.69–0.94; 10.2% v 12.2%) with no significant effect on stroke alone or all-cause mortality (HR 0.97; 95% CI 0.83–1.14; 10.3% v 10.5%). No significant benefit was detected in the primary prevention sub-group. In the secondary prevention group, the primary outcome was reduced (17.4% v 21.7%; NNT 74 per year). In an extended follow-up period of mean duration 8.6 years, there was still lower cardiovascular mortality but no difference in overall mortality with pravastatin.61
Antiphospholipid Syndrome: Management of the Obstetric Patient
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
Clinicians have sought and tried alternative “treatments” in high-risk obstetric APS cases and patients refractory to treatment with heparin LMWH and LDA. These alternative treatments are nearly always in addition to a heparin agent and LDA. Cautious interpretation of reports regarding such alternative treatments is in order because they are anecdotal or retrospective in nature and have not included proper comparison to patients matched for confounders known to be associated with adverse pregnancy outcomes of interest. Investigators have reported modestly improved pregnancy outcomes adding low-dose prednisolone (10 mg per day until 14 weeks) [47] or hydroxychloroquine (HCQ) [48] to heparin LMWH and LDA. A more recent retrospective international multicenter study of high-risk APS pregnancies concluded that the addition of HCQ treatment was associated with a significantly higher live birth rate in women with a history of one or more pregnancies refractory to conventional therapy [49], although this report did not take account of embryonic aneuploidy as a cause of miscarriage. Varying degrees of successful pregnancy outcomes have been reported in retrospective case series of high-risk or refractory obstetric APS using intravenous immunoglobulin (IVIG) infusions and/or apheresis [50–57]. Most recently, a retrospective multicenter study found that triple-positive APS patients with previous thrombosis treated with additional therapies had a significantly higher live birth rate compared to those receiving conventional therapy alone [58]. Finally, improved outcomes in APS pregnancies treated with pravastatin has been reported by one group [59].
Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats
Published in Xenobiotica, 2018
Mariana Mauro, Jose Salvador Lepera, Bruno Borsari, Jorge Manuel Vieira Capela, Natália Valadares de Moraes
The organic anion transporting polypeptides (Oatp: human; Oatp: rodents), encoded by genes in the SLCO/Slco superfamily, is a drug transporter family found mainly in hepatocytes, gut and brain which controls the access of drugs and endogenous compounds into the intracellular media (Lee et al., 2015). Erithromycin, levofloxacin, enalapril and almost all statins are among Oatp substrates. The uptake of drugs by Oatp regulates plasma drug concentration and distribution, but also display a relevant interplay with drug metabolism and elimination (Kotsampasakou et al., 2015). Pravastatin is a drug clinically used to lower blood cholesterol and triglycerides. It has been used as a probe drug for Oatp activity because its transport to hepatocytes is highly dependent on this drug transporter (Badolo et al., 2013; Hsiang et al., 1999; Nakagomi-Hagihara et al., 2007). Another reason for using pravastatin as a probe for Oatp activity in rats is based on its metabolism - pravastatin is not significantly metabolized by the cytochrome P450 (CYP) system and CYP-dependent metabolism in unlikely to be a clinically relevant elimination pathway for pravastatin (Everett et al., 1991; Hatanaka, 2000; Jacobsen et al., 1999; Watanabe et al., 2009).
Evidence and mechanisms for statin-induced cognitive decline
Published in Expert Review of Clinical Pharmacology, 2019
Brendan Tan, Franklin Rosenfeldt, Ruchong Ou, Con Stough
In another large-scale trial, the Prospective Study of Pravastatin in the Elderly at risk of Vascular Disease (PROSPER), Shephard et al. studied 5804 patients aged 70–82 years with a history of risk factors for vascular disease [32]. Patients were randomized to either statin therapy (40 mg/day pravastatin) or a placebo and followed for an average of 3.2 years. The main finding of the study was that Pravastatin significantly lowered LDL cholesterol levels. However, in the secondary outcomes of the study, it was found that Pravastatin had no significant effects on cognition as measured by the MMSE, word recall tasks or performance time. However, cognition was only a secondary outcome and the battery of tests used was not comprehensive. The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function among the elderly but is only useful as a screening test not as a sensitive test of cognitive impairment.
The role of medications in successful aging
Published in Climacteric, 2021
Beyond the lack of outcome benefit with statins in women, some trials have found an increased risk of breast cancer. In a review including seven statin trials, four had elevated HRs for breast cancer, three of which were between 1.44 and 1.65 and non-significant, but higher than the non-significant per-protocol adjusted risk estimate for CEE + MPA in the WHI trial (HR 1.20; 95% CI 0.94–1.53) [17]. One trial of pravastatin found a highly significant risk for breast cancer (HR 12.2; 95% CI 2.48–59.8) [18]. Of further concern, although (as discussed later) MHT reduces the incidence of diabetes mellitus, statins increase it. In a key trial of rosuvastatin, women had no reduction in IHD or all-cause mortality yet they had a substantially increased risk of diabetes (HR 1.49; 95% CI 1.11–2.01), while there was no such increase in men [19].
Related Knowledge Centers
- Diabetes
- Enzyme
- Statin
- Rhabdomyolysis
- Cardiovascular Disease
- Liver
- Dyslipidemia
- Pregnancy
- Hmg-Coa Reductase
- Cholesterol