Ammie J. Patel, PharmD, BCACP; and Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP
Q: SL is a 64-year-old woman taking an OTC coenzyme Q10 supplement. She asks to consult a pharmacist before starting coenzyme Q10. SL felt muscle pain, probably due to statin medication. She was told to inform all members of the medical team if she added or changed any medication to her regimen, which includes warfarin. Does coenzyme Q10 interact with warfarin?
A: Coenzyme Q10 (ubiquinone) is synthesized and found in the mitochondria of human cells. Coenzyme Q10 plays a role in energy production and regeneration of antioxidants, such as vitamin E. The results of the study showed that statin use reduces the biosynthesis of coenzyme Q10 and reduces serum concentration, although reductions in coenzyme Q10 may vary with different statins. Because coenzyme Q10 has a tolerable side effect profile, it has been used to relieve statin-related myalgias.1 Regarding the interaction between coenzyme Q10 and warfarin, studies have investigated the impact of complementary therapies on warfarin. One analysis showed that coenzyme Q10 has possible procoagulant-like vitamin K effects when taken with warfarin. Conflicting evidence from another study showed a reduced anticoagulant effect of warfarin when coenzyme Q10 was used concomitantly. As such, the SL should alert the prescriber administering its warfarin, as enhanced monitoring of the international normalized ratio (INR) is guaranteed by the combination of coenzyme Q10 and warfarin.2.3
CASE 2: OMEGA-3 FATTY ACIDS
Q: LQ is a 74-year-old who is being asked to inquire about the status of her prescription for Vascepa (icosapent ethyl). Despite submitting prior approval, her insurance company did not approve the prescription. LQ explains that her prescriber suggested the use of OTC omega-3 fatty acids if Vascepa is not covered by insurance. It already takes the highest intensity statin it can tolerate, along with omega-3 fatty acids to lower triglycerides and low-density lipoprotein cholesterol (LDL-C). How should a pharmacist advise LQ about omega-3 fatty acids?
A: Omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are derived from fish oil. Omega-3 fatty acids have been shown to reduce intestinal cholesterol absorption, reduce LDL-C and triglycerides, and improve heart health. Traditionally, the American diet contains little omega-3 fatty acids and a lot of omega-6 fatty acids.4 For the LQ indication, 2 to 4 grams per day should be used in divided doses, usually as 2 grams, 2 times a day. The results of the study showed that 1 to 5 grams of fish oil supplements per day resulted in a reduction in triglycerides of up to 51%.5 Instruct LQ to look at DHA and EPA content when selecting OTC fish oil products. For example, a product may be labeled as 1000 mg of fish oil, but the facts about the supplement may contain ingredients other than DHA and EPA, which contribute 1000 mg.6 Advise LQ to expect common adverse effects, such as fish-like belching and gastrointestinal upset. To avoid them, advise LQ to take omega-3 fatty acids with meals and to keep the capsules in the freezer or refrigerator. At doses greater than 4 grams per day, LQ may be at increased risk of bleeding. Her list of medications should be checked for the use of anticoagulants, antiplatelets, and other blood-thinning medications to ensure proper monitoring is performed.7
CASE 3: GARLIC FOR HEART HEALTH
Q: A nurse in transition at a local community hospital contacts a pharmacy to obtain a medication history for a bilateral SC patient, a 66-year-old. He notes that the patient also uses complementary therapies, such as garlic and turmeric. She reports that she is aware of the various benefits of turmeric, but asks about the benefits of garlic in heart health. What information should a pharmacist provide?
A : Garlic is used as adjunctive therapy for diabetes, hyperlipidemia, hypertension, and immune health. Allicin and S-allyl cysteine are active garlic compounds that have pharmacological effects. Garlic prevents lipid oxidation, which may play a role in its lipid lowering and antihypertensive activity. Garlic also stimulates the production of the vascular gas transmitter hydrogen sulfide and enhances the regulation of nitric oxide, which further contributes to its antihypertensive effects. Garlic has been studied using aged garlic or garlic powder extracts, but enteric acid-coated products are also available.8 Regarding hypertension, the results of the study showed that garlic on average reduced diastolic blood pressure (DBP) and systolic blood pressure (SBP) in patients with initial hypertension by 6.1 mmHg and 8.7 mmHg, respectively, and also had a relatively modest effect on patients who did not have initial hypertension.9 Another meta-analysis investigating the effects of garlic on hypertension showed a mean reduction in DBP and SBP of 3.82 mmHg and 9.36 mmHg, respectively.10 The results of the study also showed that garlic reduced total cholesterol levels by 15 to 19.63 mg / dL in patients with an initial total cholesterol greater than 200 mg / dL.11 Garlic is well tolerated, but can cause nausea, acid reflux, vomiting, and heartburn early in therapy and in higher doses. Body odors and garlic odor have also been reported.8 Significant drug interactions with garlic include increased INR when used with warfarin and decreased efficacy of oral contraceptives.12
CASE 4: RED Yeast rice
Q: GL is a 56-year-old woman inquiring about cholesterol-lowering drugs. She talked to statins about statins and decided to try lifestyle changes and natural products before committing to lifelong medications. GL’s sister was on a statin and as a result had severe muscle cramps. GL pie for red yeast rice. What should a pharmacist advise?
A: Red yeast rice grows on fermented rice, and its components include a lovastatin analogue (monacolin K).13 In traditional Chinese medicine, it is used to lower cholesterol through the mechanism of lovastatin and bile acid secretion properties. The results of the study showed that it reduces LDL-C, total cholesterol and triglycerides and makes modest changes in high-density lipoprotein cholesterol. A second systematic review of yeast rice versus simvastatin found similar effects on all biological lipid markers. Red yeast rice is dosed in an amount of 1.2 to 2.4 grams per day in 2 divided doses.14 Like statins, red yeast rice is contraindicated for use in pregnancy. Side effects of red yeast rice include allergic reactions, bloating, elevated liver enzymes, bloating, headache and heartburn. Users of strong alcohol should avoid yeast rice because of the overlapping risk of liver toxicity. Post-onset monitoring should include liver function tests.15 Advise GL on the similarities between prescription drugs with statins and red yeast rice. If it starts with yeast rice, refer the GL to your doctor to perform initial and post-follow-up of lipids and liver function tests for efficacy and safety.15
Ammie J. Patel, PharmD, BCACP, is a clinical assistant professor of pharmaceutical practice and administration at Ernest Mario School of Pharmacy in Rutgers, New Jersey State University in Piscataway, and an outpatient care specialist at RWJ Barnabas Health Primary Health in Shrewsbury and Eatontown, New Jersey.
Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP, he is a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers, New Jersey State University, and a clinical pharmacist for transition at Morristown Medical Center in New Jersey.
- Banach M, Serban C, Ursoniu S, et al; Lipid and Blood Pressure Meta-Analysis Group (LBPMC). Plasma statin therapy and plasma coenzyme Q10 concentrations – a systematic review and meta-analysis of placebo-controlled trials. Pharmacol Res. 2015; 99: 329-336. doi: 10.1016 / j.phrs.2015.07.0082.
- Shalansky S, Lynd L, Richardson K, Ingaszewski A, Kerr C. Warfarin-related bleeding risk and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007; 27 (9): 1237-1247. doi: 10.1592 / phco.27.9.12373.
- Spigset O. Reduced effect of warfarin caused by ubidecarenone. Lancet. 1994; 344 (8933): 1372-1373. doi: 10.1016 / s0140-6736 (94) 90736-64.
- Eslick GD, Howe PRC, Smith C, Priest R, Bensoussan A. Benefits of fish oil supplements in hyperlipidemia: a systematic review and meta-analysis. Int J Cardiol. 2009; 136 (1): 4-16. doi: 10.1016 / j.ijcard.2008.03.0925.
- Leslie MA, Cohen DJA, Liddle DM, Robinson LE, MaDWL. Review of the effect of omega-3 polyunsaturated fatty acids on the level of triacylglycerol in the blood in normal-lipidemic and borderline hyperlipidemic individuals. Lipids Health Dis. 2015; 14: 53. doi: 10.1186 / s12944-015-0049-76.
- Melanson SF, Lewandrowski EL, Flood JG, Lewandrowski KB. Measurement of organochlorine in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and literature review. Arch Pathol Lab Med. 2005; 129 (1): 74-77. doi: 10.1043 / 1543-2165 (2005) 129<74:MOOICO>2.0.CO; 27.
- Weitz D, Weintraub H, Fisher E, Schwartzbard AZ. Fish oil for the treatment of cardiovascular diseases. Cardiol Rev. 2010; 18 (5): 258-263. doi: 10.1097 / CRD.0b013e3181ea0de0
- Hosseini A, Hosseinzadeh H. Review of the effects of Allium sativum (garlic) on metabolic syndrome. J Endocrinol Invest. 2015; 38 (11): 1147-1157. doi: 10.1007 / s40618-015-0313-89.
- Ried K. Garlic lowers blood pressure in people with hypertension, regulates serum cholesterol and stimulates immunity: an updated meta-analysis and review. J Nutr. 2016; 146 (2): 389S-396S. doi: 10.3945 / jn.114.20219210.
- Rohner A, Ried K, Sobenin IA, Bucher HC, Nordmann AJ. Systematic review and meta-analysis of the effects of garlic preparations on blood pressure in people with hypertension. Am J Hypertens. 2015; 28 (3): 414-423. doi: 10.1093 / ajh / hpu16511.
- Ried K, Toben C, FaklerP. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013; 71 (5): 282-299. doi: 10.1111 / nure.1201212.
- Boullata J. Interactions of natural health products with drugs. Nutr Clin Pract. 2005; 20 (1): 33-51. doi: 10.1177 / 01154265050200013313.
- Gerards MC, Terlou RJ, Yu H, Koks CHW, Gerdes VEA. The traditional Chinese lipid-lowering agent red yeast rice results in a significant reduction in LDL, but safety is uncertain – systematic review and meta-analysis. Atherosclerosis. 2015; 240 (2): 415-423. doi: 10.1016 / j.atherosclerosis.2015.04.00414.
- Venus CV, Venus JV, Wortham DC, Thompson PD. Efficacy of red yeast rice in lipid lowering in a statin intolerant population. Am J Cardiol. 2010; 105 (5): 664-666. doi: 10.1016 / j.amjcard.2009.10.04515.
- Halbert SC, French B, Gordon RY, et al. Tolerance of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance. Am J Cardiol. 2010; 105 (2): 198-204. doi: 10.1016 / j.amjcard.2009.08.672