Ammie J. Patel, PharmD, BCACP; and Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP
Q: SL is a 64-year-old woman who is picking up an OTC coenzyme Q10 supplement. She asks to consult the pharmacist before initiating coenzyme Q10. SL has been experiencing muscle aches and pain, possibly because of her statin medication. She has been told to inform all health care team members if she adds or changes any medications to her regimen, which includes warfarin. Does coenzyme Q10 interact with warfarin?
A: Coenzyme Q10 (ubiquinone) is synthesized and present in mitochondria of human cells. Coenzyme Q10 plays a role in energy production and regeneration of antioxidants, such as vitamin E. Study results have shown that statin use decreases coenzyme Q10 biosynthesis and lowers serum concentrations, although decreases in coenzyme Q10 may differ among various statins. Because coenzyme Q10 has a tolerable adverse effect profile, it has been used to mitigate myalgias related to statin use.1 In terms of 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 vitamin K–like procoagulant effects when taken with warfarin. Conflicting evidence from another study showed diminished anticoagulant effect of warfarin when coenzyme Q10 was used concomitantly. As such, SL should alert the prescriber managing her warfarin, as increased international normalized ratio (INR) monitoring is warranted with the combination of coenzyme Q10 and warfarin.2,3
CASE 2: OMEGA-3 FATTY ACIDS
Q: LQ is a 74-year-old woman who calls to inquire about the status of her Vascepa (icosapent ethyl) prescription. Despite submission of prior authorization, her insurance did not approve the prescription. LQ explains that her prescriber suggested use of OTC omega-3 fatty acids if the Vascepa was not covered by insurance. She is already taking the highest intensity of statin she can tolerate, along with omega-3 fatty acids for triglyceride and low-density lipoprotein cholesterol (LDL-C) reduction. How should the pharmacist counsel LQ on omega-3 fatty acids?
A: Omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are sourced from fish oil. Omega-3 fatty acids have shown to decrease intestinal cholesterol absorption, reduce LDL-C and triglycerides, and improve cardiac health. Traditionally, the American diet is low in omega-3 fatty acids and high in omega-6 fatty acids.4 For LQ’s indication, 2 to 4 grams per day in divided doses should be used, typically as 2 grams, 2 times per day. Study results have shown that 1 to 5 grams per day of fish oil supplements resulted in triglyceride decreases of up to 51%.5 Instruct LQ to look at the DHA and EPA content when choosing an OTC fish oil product. For example, the product may be labeled as 1000 mg fish oil, but the supplement facts may include other ingredients besides DHA and EPA that contribute to the 1000 mg.6 Counsel LQ to expect common adverse effects, such as belching with fish-like breath and gastrointestinal distress. To avoid these, advise LQ to take the omega-3 fatty acids with meals and to store the capsules in a freezer or refrigerator. With doses higher than 4 grams per day, LQ may be at increased risk of bleeding. Her medication list should be screened for use of anticoagulants, antiplatelets, and other blood-thinning medications to ensure that appropriate monitoring is implemented.7
CASE 3: GARLIC FOR HEART HEALTH
Q: The transitions-of-care nurse at a local community hospital contacts the pharmacy to obtain the medication history for mutual patient SC, a 66-year-old man. In doing so, she notes that the patient has also been using 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 the pharmacist provide?
A : Garlic is used as complementary therapy for diabetes, hyperlipidemia, hypertension, and immune health. Allicin and S-allyl cysteine are the active compounds of garlic that exert pharmacologic 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 gasotransmitter hydrogen sulfide and enhances the regulation of nitric oxide further contributing to its antihypertensive effects. Garlic has been studied via aged garlic extracts or powdered garlic, but enteric coated products are also available.8 With respect to hypertension, study results have shown that on average, garlic reduced diastolic blood pressure (DBP) and systolic blood pressure (SBP) in patients with baseline hypertension by 6.1 mmHg and 8.7mmHg, respectively, and also had a relatively modest effect on patients who did not have baseline hypertension.9 Another meta-analysis investigating the effects of garlic on hypertension showed mean reductions in DBP and SBP of 3.82 mmHg and 9.36 mmHg, respectively.10 Study results have also shown that garlic reduced total cholesterol levels by 15 to 19.63 mg/dL in patients with baseline total cholesterol greater than 200 mg/dL.11 Garlic is well tolerated but may cause nausea, acid reflux, vomiting, and heartburn early in therapy and at higher doses. Garlic body odor and breath have also been reported.8 Notable drug interactions with garlic include an increased INR when used with warfarin and decreased effectiveness in oral contraceptives.12
CASE 4: RED YEAST RICE
Q: GL is a 56-year-old woman who is inquiring about medications to lower her cholesterol. She had discussed statins with her primary care provider and decided to try lifestyle modifications and natural products before committing to a lifelong medication. GL’s sister had been on a statin and experienced severe muscle cramps as a result. GL asks about red yeast rice. What should the pharmacist advise?
A: Red yeast rice grows on fermented rice, and its components include lovastatin analogue (monacolin K).13 It has been used in traditional Chinese medicine to lower cholesterol via its lovastatin mechanism and its bile acid excretion properties. Study results have shown it to decrease LDL-C, total cholesterol, and triglycerides and to make modest changes in high-density lipoprotein cholesterol. Another systematic review of red yeast rice versus simvastatin identified similar effects on all lipid biomarkers. Red yeast rice is dosed as 1.2 to 2.4 grams per day in 2 divided doses.14 Like statins, red yeast rice is contraindicated to use in pregnancy. Adverse effects of red yeast rice include allergic reactions, bloating, elevated liver enzymes, flatulence, headache, and heartburn. Heavy alcohol users should avoid red yeast rice because of the overlapping risk of liver toxicity. Monitoring after initiation should include liver function tests.15 Counsel GL on the similarities between prescription statin medication and red yeast rice. If she initiates red yeast rice, refer GL to her physician to conduct baseline and follow-up monitoring of lipids and liver function tests for efficacy and safety.15
Ammie J. Patel, PharmD, BCACP, is a clinical assistant professor of pharmacy practice and administration at Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway, and an ambulatory care specialist at RWJ Barnabas Health Primary Care in Shrewsbury and Eatontown, New Jersey.
Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP, is a clinical associate professor at Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey, and a transitions-of-care clinical pharmacist at Morristown Medical Center in New Jersey.
- Banach M, Serban C, Ursoniu S, et al; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. 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. Risk of warfarin-related bleeding events 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 effectof 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 supplementation 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. A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic 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 organochlorines in commercial over-the-counter fish oil preparations: implications for dietary and therapeutic recommendations for omega-3 fatty acids and a review of the literature. 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 disease. Cardiol Rev. 2010;18(5):258-263. doi:10.1097/CRD.0b013e3181ea0de0
- Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest. 2015;38(11):1147-1157. doi:10.1007/s40618-015-0313-89.
- Ried K. Garlic lowers blood pressure in hypertensive individuals, 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. A systematic review and metaanalysis on the effects of garlic preparations on blood pressure in individuals 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. Natural health product interactions with medication. Nutr Clin Pract. 2005;20(1):33-51. doi:10.1177/01154265050200013313.
- Gerards MC, Terlou RJ, Yu H, Koks CHW, Gerdes VEA. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain–a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-423. doi:10.1016/j.atherosclerosis.2015.04.00414.
- Venero CV, Venero JV, Wortham DC, Thompson PD. Lipid-lowering efficacy of red yeast rice in a population intolerant to statins. Am J Cardiol. 2010;105(5):664-666. doi:10.1016/j.amjcard.2009.10.04515.
- Halbert SC, French B, Gordon RY, etal. Tolerability 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