The Family Practice Newsletter
The Ohio University College of Osteopathic Medicine The Ohio Northern University Raabe College of Pharmacy Doctors Hospital Family Practice
Volume 5, Issue 6
Fish Oil- A Good Catch
Kelly Stanforth, Pharm.D. Hypertriglyceridemia has been shown to be an independent risk factor for developing coronary heart disease (CHD). As triglyceride (TG) levels rise above 200 mg/dL, quantities of atherogenic remnant lipoproteins increase risk of CHD beyond that of LDL cholesterol alone. The initial treatment for hypertriglyceridemia includes lifestyle modifications and strict glycemic control. When the prior measures are unsuccessful, pharmacologic treatment may be considered, especially in patients with TG measurements greater than 200 mg/dL. Pharmacological treatment options for hypertriglyceridemia include niacin, fibric acid derivatives, fish oil, and statins for patients who also have elevated LDL-C levels. The use of fish oil for the treatment of hypertriglyceridemia has gained popularity since 2002, when the American Heart Association (AHA) recommended that individuals with high levels of TG be prescribed two to four grams of omega-3 fatty acid daily. Studies have shown that fish oils from supplements can lower TG levels by 20 to 50 percent. Omacor® (omega-3-acid ethyl esters) is the first prescription fish oil product approved by the FDA for adjunctive treatment in patients with TG levels greater than 500 mg/dL. Omacor ® is a combination of highly purified and concentrated ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenioc acid (DHA). EPA and DHA interfere with the liver’s ability to synthesize TG, as EPA and DHA are alternative substrates for enzymes responsible for synthesis. The FDA approved Omacor® based on the safety and efficacy of eight double-blind, placebo controlled trials. Pooled data from these eight trials demonstrated a median percentage decrease in TG of 17.3 to 47.7 percent in patients receiving a 4gm per day dose of Omacor®. Additionally, Omacor® exhibited an overall TG reduction of 28 percent compared to an increase of 2.5 percent in the placebo group. Of note, a significant increase in LDL-C with Omacor® was observed in all studies. It is proposed that this increase is due to a shift from smaller, more atherogenic LDL particles to larger, less atherogenic particles. Unfortunately, LDL particle size was not evaluated in any of the pooled trials. Patients should be placed on an appropriate lipid-lowering diet before initiating Omacor® and should continue the diet during treatment with the medication. Omacor® is prescribed as 4 gm per day, which can be taken as a single dose of four capsules or as two capsules twice a day. Omacor® has been well tolerated in clinical trials with the most commonly reported side effects being dyspepsia, burping and taste changes (primarily fishy taste). Significant drug-drug interactions via the cytochrome P450 enzyme system are not expected with Omacor ®. However, some studies have demonstrated prolonged bleeding times when omega-3 fatty acids have been utilized concomitantly with anticoagulants. Omacor ® is contraindicated in patients hypersensitive to any component of the drug or in patients with an allergy to fish. An increase in alanin aminotransferase (ALT) and low-density lipoprotein (LDL-C) levels have been observed in clinical trials. It is recommended that ALT and LDL-C levels are monitored periodically during treatment. Omacor ® should be discontinued in patients who fail to produce an adequate response after two months of therapy. In November of 2005, Reliant Pharmaceuticals, the manufacturer of Omacor ® released a warning regarding potential interchange for Omacor® prescriptions with Amicar® (aminocaproic acid), a fibrinolysis inhibitor. Errors are thought to have occurred due to the similar nature of the names of the two medications and the fact they are available in a 1 gm dosage strength. Practitioners are encouraged to clarify the medication name when receiving or transferring a prescription for either of these medications.
References: 1. Duggal N, Tom WC. New drug: omacor (omega-3 acid ethyl esters). Pharm Letter 2005; 21: detail document # 2110033. 2. Fish and omega-3 fatty acids. American Heart Association Recommendation. Available at http://americanheart.org/presenter.jhtml?identifier=4632. 3. Company warning: Omacor-amicar mix-ups. Institute for Safe Medications (ISMP) medication safety alert. Available at http://www.ismp.org/Newsletters/acutecare/articles/20051201_2.asp.
February, 2006
Extended Release Products Exposed
Kelly Stanforth, Pharm. D. POP QUIZ! s patient has been non-compliant with her beta blocker regimen of metoprolol tartate 50mg BID; you feel that if she were prescribed a once daily modified release product she may be more apt to stick with her regimen. What dose of metoprolol succinate (Torpol XL®) should you prescribe? A. Torpol XL® 100mg QDay B. Torpol XL® 50mg QDay More and more medications have been released in extended-release preparations, which can be taken once daily as opposed to multiple times a day. Extended release products offer multiple benefits such as producing sustained blood levels of drug, reducing adverse effects, and improving patient adherence. Many terms are used to describe modified release products including extended release(ER), prolonged release, controlled release(CR), controlled delivery, slow release and sustained release(SR). By definition these preparations have a reduced rate of release of active substance and are interchangeable as terms. Delayed release products are modified release but by definition are not extended release products. These preparations release a discrete amount of medication some time after drug administration. For example enteric coated aspirin exhibits a lag time during which little or no drug absorption of the medication occurs. Unfortunately there is a shady side to modified release medications. Many modified release medications are marketed with the same name as their shorter acting counterpart but with an additional term such as “SR” for sustained release or “XL”. This is largely due to the fact that pharmaceutical companies have invested large sums of money in medication names and are reluctant to utilize alternative names for modified release preparations. However, this increases the likelihood that the patient is not getting the right medication regimen, as the suffix “SR” or “XL” are easily left out of the patients medical record at the doctors office. Errors in prescribing modified release products arise when the long acting preparation of medication is given in the dose intended for the short acting medication or vice versa. This type of medication error can result in a patient receiving an inadequate dose of medication, too much medication, or even death. A study on prescribing errors by Lesar found that 70 % of prescribing errors associated with modified release preparations were from failure to specify the use of a modified release product on physician orders. An additional 12 % of errors involved prescribing modified release formulations to be administered by tube, which can also result in adverse events as these preparations become immediately available when the medication is pulverized. Most modified release products cannot be split in half or crushed. These actions will affect the absorption of the medication, causing the patient to get too much too fast, leading to supratherapeutic levels. Errors involving modified release products can be tackled at the individual provider level. Extra caution should be taken when prescribing a medication that is available in both short and long acting formulations. In particular, be sure to include the appropriate suffix to the medication name when trying to decrease the number of medications a patient has to take each day. The answer to the quiz is A. Metoprolol succinate is an extended release tablet intended for once-a-day administration. When switching from immediate release metoprolol tartate tablet to extended release metoprolol succinate, the same total daily dose of extended release metoprolol succinate should be used.
References 1. 2. 3. Sansom LN. Oral extended-release products. Aust Prescr 1999; 22: 88-90. Lesar T. Prescribing errors involving medication dosage forms. JGIM 2002; 17: 579-586. Bates. Sustained-release preparations and medication errors. JGIM 2002; 17: 657-658.
Edited by Stephanie Gibson, Pharm.D. Comments can be sent to sgibson@ohiohealth.com