Phenytoin: A Review

By Mitchell Tucci

Phenytoin is a an anticonvulsant used for both treatment for and prophylaxis of seizures. There are multiple dosage forms including a chewable immediately release (IR) tablet and an extended release (ER) capsule. These formulations are not equivalent and have different half lives; 22 hours for the ER and 14 hours for the IR. Time to peak concentration is also different between the two formulations with levels reaching their max in 4-12 hours for the ER and 1.5-3 hours for the IR formulation. In addition, the two formulations do not have the same dose conversion; the ratio of dose of phenytoin is 0.92:1 for the phenytoin salt (ER): phenytoin tablet (IR).

Phenytoin is also unique due to a very high protein binding up to 92%. Because of this property, a corrected phenytoin level is calculated to account for changes in blood protein (albumin). The equation for this is as follows:

In patients with end stage renal disease (ESRD), phenytoin binding to albumin is impaired. We adjust the equation to:

Because of phenytoin‘s long half life, fluctuations in serum levels with long term administration are very minimal. Levels should be drawn in cases of suspected toxicity or non-compliance and can be drawn regardless of the dosing time. If monitoring levels after a dose adjustment, a trough should be taken right before the next dose. The appropriate levels for a corrected phenytoin should be between 10-20 mg/L.

References:

1. Product Information: Dilantin(R) oral extended-release capsules, phenytoin sodium oral extended-release capsules. Pfizer, Inc. (per DailyMed), New York, NY, 2015
2. Product Information: DILANTIN(R) INFATABS(R) oral chewable tablets, phenytoin oral chewable tablets. Parke-Davis (per DailyMed), New York, NY, 2011.
3. http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307

Iron Deficiency: Which Iron to Choose?

By Mitchell Tucci

Anemia is a group of diseases characterized by either decreased hemoglobin (Hgb)
or decreased red blood cells (RBC) or RBC volume which results in a decrease
in the blood’s ability to carry oxygen. The World Health Organization defines anemia as a Hgb < 13 g/dL in men and < 12 g/dL in women. There are a number of different causes of anemia including vitamin deficiencies, blood loss and renal disease. However, one of the most common causes of anemia is one that a pharmacist’s knowledge can particularly come help with: iron deficiency.

A pharmacist can help navigate the many different types and formulations of iron supplements to ensure the best possible outcome for their patients. Iron supplementation can be broken down into two broad categories: oral and intravenous.

Oral Iron Supplemention

Most patients with chronic iron deficiency anemia will need to take 100-200 mg of elemental iron. Pharmacists must remember that each iron product is different and in order to determine correct dosage the percent elemental iron must be taken into consideration. Cost and absorption are two more important factors to consider when choosing a product. Iron supplements can cause GI upset which can be managed by splitting the total dose into divided doses. The following table can be used to make a more informed decision about which iron product is best!

Intravenous Iron Supplementation

In the acute setting IV supplementation is often given as a faster approach to patients whose iron and Hgb levels might be dangerously low. There are currently four intravenous iron products available in the united states. Important factors to consider when choosing a product are cost, time needed for administration, number of doses needed to treat and when/if a test dose is needed to be administered first. Allergic and infusion reactions have both been reported with IV use of iron and infusions should be started at a low rate with careful observation. Patients with a history of medication allergies or asthma can be pre-medicated with methylprednisone. The following table can be used to help determine which IV formulation is best for your patient!

References:

Clinical Resource, Comparison of Oral Iron Supplements. Pharmacist’s Letter/Prescriber’s Letter. March 2017.

https://www.uspharmacist.com/article/parenteral-irons-indications-and-comparison

http://www.micromedexsolutions.com.

Who Is at Risk for Anemia? National Heart Lung and Blood Institute. https://www.nhlbi.nih.gov/health/health-topics/topics/anemia/atris

https://www.uptodate.com/contents/approach-to-the-adult-with-anemia?search=anemia%20workup&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

Atenolol: A Review

By: Mitchell Tucci

The world of medicine is always changing. With the addition of approximately 50 new FDA approved drugs every year, therapies for diseases are constantly in flux which can make the navigating the already complex health care field even more challenging. What was once the preferred drug of choice for a disease can quickly be replaced with the emergence of a new drug trial. It’s important to compare therapies to one another in clinical trials so we are able to choose the best therapies for our patients.

Let’s discuss some of the research comparing agents in a drug class that I’m sure you are all aware of: Beta Blockers.

 

In 2004, a meta-analysis reviewed five randomized control trials (RCTs) with a combined 17,671 patients comparing atenolol to other antihypertensives. What was found was actually quite profound: a significantly higher all cause mortality (RR: 1.13 [95% CI 1.02-1.25]) with atenolol treatment. A similar more recent review from 2014 found even more alarming evidence against atenolol: an increased risk of stroke compare to other hypertensive agents in elderly patients (1.17 [1.05-1.30]).

The same 2004 meta-analysis also reviewed four RCTs with a combined 6,825 patients comparing atenolol to placebo. It was found that although there were major differences in BP lowering with atenolol, no outcome differences were found between all-cause mortality (RR 1.01 [95% CI 0.89-1.15]), cardiovascular mortality (0.99 [0.83-1.18]), or myocardial infarction (0.99 [0.83-1.19]). Think about that for a minute. As a part of the medical team, controlling blood pressure (BP) is a critical part of treating a patient with hypertension. One would assume that lowering BP with any agent would decrease the risk of a major cardiovascular event. But the exact opposite was shown with atenolol: no protection despite the lowered BP. This is one of the reasons testing for clinical outcomes (mortality & morbidity) is so crucial in studies! 

 

As we can see from the findings above, agents within the same drug class can have vastly different outcomes! As a pharmacist it is crucial to know the differences to add value to the health care team.

References:

1. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: Is it a wise choice? Lancet. 2004 Nov; 364: 1684-89. doi: 10.1016/S0140-6736(04)17355-8

2. Kuyper LM, Khan NA. Atenolol vs nonatenolol β-blockers for the treatment of hypertension: a meta-analysis. Can J Cardiol. 2014 May; 30(5 Suppl): S47-53. doi: 10.1016/j.cjca.2014.01.006.

3. Zhang Y, Sun N, Jiang X, Xi Y. Comparative efficacy of β-blockers on mortality and cardiovascular outcomes in patients with hypertension: a systematic review and network meta-analysis. Journal of the American Society of Hypertension. 2017; 11(7): 394-401. doi: 10.1016/j.jash.2017.05.001

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