Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA program.
WHAT ARE THE NEW
DOSING RESTRICTIONS FOR
SIMVASTATIN?
The FDA has released new dosing restrictions for simvastatin (Zocor), and many clinicians believe these are long overdue. Simvastatin is available in 5- to 80-mg doses; however, the 80-mg dose results in significantly more myopathies when compared to lower doses and other statins. These myopathies can range from myalgias to myositis to overt rhabdomyolysis.
Although myopathies resulting from simvastatin are known to be dose-dependent, a recent trial comparing simvastatin 80 mg to simvastatin 20 mg prompted the labeling change.1 This trial enrolled more than 12,000 patients and found that the risk of simvastatin-related myopathy increased approximately 10-fold with the 80-mg daily dose. The risk is greatest during the first year of therapy and in patients with a genetic variation of the transporter that is responsible for hepatic uptake of statins.
Because simvastatin is metabolized by the cytochrome P-450 system (CYP), another risk factor for simvastatin-
induced myopathies includes concurrent drug therapy, particularly with medications that inhibit CYP3A4. Despite dose limitations and warnings of drug interactions in the product labeling, patients continue to receive higher than recommended doses of simvastatin. The FDA has responded by proposing dose restrictions of simvastatin when used in combination with certain medications (see Table: Drugs that interact with simvastatin in the online version of this article).
The bottom line is the risk of simvastatin 80 mg exceeds the benefits, and safer alternatives are available. If patients are not reaching their LDL goal on simvastatin 40 mg, switch to a more potent agent such as atorvastatin or rosuvastatin. If simvastatin is contraindicated because of a drug interaction, prescribe a statin that is less likely to interact with other medications (examples include pravastatin, fluvastatin, pitavastatin, or rosuvastatin; check product labeling for specific interactions). Patients who have been stabilized on simvastatin 80 mg daily for more than 1 year may be maintained on this dose if they do not have any evidence of muscle toxicity. If cost is a concern, keep in mind that Lipitor will go generic later this year.
WHAT IS APPROPRIATE MONITORING OF AMIODARONE THERAPY?
Amiodarone is a class III antiarrhythmic with a unique pharmacokinetic profile, multiple drug interactions, and a plethora of adverse effects. Because amiodarone has a large volume of distribution, is very lipophilic, and has an extended half-life of approximately 52 days (range 26-107 days), it can accumulate and cause toxicity in multiple organs. The long half-life also means that adverse effects may persist after the drug is discontinued.
Amiodarone monitoring requirements are related to its adverse effect profile. Although relatively rare, pulmonary toxicity is responsible for most deaths associated with amiodarone therapy. Onset is often insidious and nonspecific (subacute cough and dyspnea). Elevated hepatic transaminases are common (up to 30% of patients), but fatal hepatitis and cirrhosis have also occurred. Amiodarone labeling includes a black box warning outlining the risk of fatal hepatic and pulmonary toxicities.
Other common adverse effects include thyroid dysfunction, skin changes (bluish-gray skin discoloration and photosensitivity), and GI complaints (nausea, constipation, anorexia). CNS effects are variable but may include tremor, ataxia, paresthesias, peripheral neuropathy,
and sleep disturbances. As with any antiarrhythmic drug, changes in cardiac conduction may occur, with bradycardia and atrioventricular block being the most common. Almost all patients on chronic amiodarone therapy have benign corneal microdeposits; however, halo vision (especially at night) and optic neuritis occur infrequently.
Although guidelines for monitoring
amiodarone therapy have been established,2 adherence is low. Remembering the monitoring parameters and adverse effects associated with amiodarone therapy is difficult, but PAs should know they exist and create a checklist to ensure each patient is being appropriately monitored (see Table: Amiodarone monitoring in the online version of this article). It is imperative to recognize common adverse drug
effects and resist the temptation to assign a new diagnosis without first reviewing drug therapy and eliminating iatrogenesis. JAAPA
Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA program.
REFERENCES
1. SEARCH Collaborative Group. Lancet. 2010;376(9753):
1658-1669.
2. Goldschlager N, et al. Heart Rhythm. 2007;4(9):1250-1259.