Ambulatory Care: Hypertension
Kate R. Gerrald, PharmD, BCPS
A 65-year-old man presents to your hypertension clinic with a past medical history of type 2 diabetes and hypertension. Vital signs in clinic today are blood pressure 134/80 mm Hg, heart rate 78 bpm. Current medications include Metformin 1000 mg twice daily, Levemir 40 units daily, Novolog 10 units before each meal, lisinopril 40 mg daily, and simvastatin 40 mg daily. At the last visit, his lisinopril was increased due to BP of 140/85 mm Hg and his A1C was 7.2%.
Since the release of JNC 7 guidelines in 2004, the blood pressure goal for patients with type 2 diabetes has been set as less than 130/80 mm Hg based on cohort analyses from the HOT trial and UKPDS groups, which has been additionally recommended by the American Diabetes Association up until 2011.
The importance of BP control has long been known, particularly in patients with type 2 diabetes who are already at high risk of cardiovascular disease; however, no large randomized trial has shown reduction in cardiovascular mortality with lowering BP to less than 140/80 mm Hg. Several large trials published since JNC 7 have called into question our current guideline-recommended goals.
The ACCORD BP trial included 4733 high-risk patients with type 2 diabetes and randomized them to tight systolic BP control (<120 mm Hg, achieved 119/64 mm Hg) or standard control (<140 mm Hg, achieved 133/70 mm Hg). There was no difference found between the 2 groups in the composite outcome of nonfatal myocardial infarction, stroke, and cardiovascular disease death (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.73-1.06; P = .2).
Potential confounding of patients also randomized to intensive glycemic control was demonstrated in a predefined subgroup analysis which showed intensive BP control may be of benefit in those not randomized to intensive glycemic control (A1C <6%). A post hoc analysis of the INVEST trial refuted the hypothesis that patients who achieved systolic BP less than 130 mm Hg would have reduced risk of cardiovascular events compared with those achieving systolic BP 130 to 140 mm Hg (adjusted HR 1.11; 95% CI 0.93-1.32; P = .24). The ADVANCE trial included 11,140 patients with type 2 diabetes and 1 additional cardiovascular risk factor. Patients were randomized to treatment with ACE/thiazide diuretic combination or placebo instead of specific BP goals. Those in the active treatment arm achieved BP of 5.6/2.2 mm Hg less than the placebo arm and no significant reduction was seen in the composite outcome of macrovascular and microvascular events; however, reduction was seen in death and cardiovascular death.
The American Diabetes Association 2011 Standards of Care reiterated the systolic goal of less than 130 mm Hg for most patients, but noted that most benefit is seen when systolic BP is less than 140 mm Hg. The ACCORD BP trial is the only study to formally determine the difference in outcomes between tighter and less stringent BP goals. The question has not been raised about the diastolic goal of less than 80 mm Hg. In our case above, it would be reasonable to continue current treatment for this patient and not introduce further medications until BP becomes uncontrolled at greater than 140/80 mm Hg. Further clarification of these goals and incorporation of recent literature is expected in JNC 8 guidelines, due out in 2012.
Kate R. Gerrald, PharmD, BCPS, is assistant professor of pharmacy practice at the Presbyterian College School of Pharmacy in Clinton, South Carolina.
Improving Safety for Pediatric Patients: Acetaminophen Concentration Standardization
Allison Beck Blackmer, PharmD, BCPS
Case JS, a 3-year-old child weighing 16 kg, was recently hospitalized for acute appendicitis. Upon discharge, the physician instructed JS’s mother to purchase OTC acetaminophen and to administer 7.5 mL (1.5 teaspoonfuls) 4 times per day for post-appendectomy pain. What can the hospital pharmacist add to the instructions?
An estimated 12% of children younger than 11 years of age take acetaminophen in any given week.1 This OTC antipyretic/ analgesic is first-line therapy for pain and fever in children at a dose of 10 to 15 mg/ kg every 4 to 6 hours as needed (maximum: 5 doses per 24- hour period).2,3 Commercially available acetaminophen has historically been supplied in 2 formulations: 1) concentrated acetaminophen 80 mg/0.8 mL, and 2) acetaminophen elixir 160 mg/5 mL.1,3
Without specific instructions, JS’s mother might inadvertently administer a significantly higher dose than intended. If she purchased the 80 mg/0.8 mL rather than the 160 mg/5 mL concentration and gave 1.5 teaspoonfuls, she would administer her child a 3-fold overdose by giving 750 mg rather than the intended 240 mg dose.
Acetaminophen-associated medication errors are commonly reported to result from improper administration of concentrated acetaminophen drops instead of less concentrated acetaminophen elixirs, in addition to confusion with units of measure (ie, teaspoonfuls vs dropperfuls).4-7
A pharmaceutical industry—wide initiative began in mid-2011 in response to a 2009 FDA Advisory Committee recommendation for standardization of acetaminophen concentrations for children less than 12 years of age.1,8-11 Commercially available acetaminophen products will be converted to 1 standardized concentration: 160 mg/5 mL. Additionally, age-appropriate, accurate administration devices with a standardized unit of measure (mL) will be included with all medication packages. These changes are specifically aimed at improving patient safety by decreasing acetaminophen- associated medication errors.
While the transition to 1 standardized strength will ultimately lead to improved patient safety, during the period of transition both formulations continue to be on pharmacy shelves and in homes. Pharmacists are uniquely positioned to safely shepherd this change and to provide appropriate education to providers and caregivers alike. By maintaining awareness of the concentrations of products, appropriate administration devices, and effective provider/caregiver education, pharmacists play an important role in promoting safe medication practices for children and reducing pediatric medication errors.
Allison Beck Blackmer, PharmD, BCPS, is clinical assistant professor at the University of Michigan College of Pharmacy and clinical pharmacy specialist-pediatric surgery at the C.S. Mott Children’s Hospital.
Oncology: Neuropathic Pain
Alex Ganetsky, PharmD
CL is a 42-year-old woman with a history of left-sided breast cancer with lymph node involvement treated with mastectomy, lymphadenectomy, and adjuvant chemotherapy, and presents to the pain and palliative care clinic complaining of left arm pain. CL describes having numbness across her left axilla, significant burning, and a “pins and needles” sensation down the left medial aspect of her arm. What is the appropriate treatment for this patient’s neuropathy?
Cancer patients have a high predisposition for developing neuropathic pain, often manifesting as a dose-limiting toxicity and quality-of-life impairer. Optimal pharmacologic management of neuropathic pain remains an ongoing controversy, as guidelines have yet to offer consistent recommendations. 1
A sensible first-line approach is to initiate therapy with gabapentin or pregabalin. Slow titration of the dose is warranted to ameliorate the development of central nervous system toxicities. Patients with psychosocial issues may benefit from a tricyclic antidepressant as first-line therapy because of their dual antidepressant and anti-neuropathic potential. Second-line therapies include duloxetine, venlafaxine, opioid analgesics, and lidocaine patches.2 Methadone, an opioid analgesic with concurrent anti-neuropathic potential, has also demonstrated efficacy in treating peripheral neuropathy.3
CL was initially treated with gabapentin 100 mg twice daily and titrated over several months to 1200 mg 3 times a day. Initial pain relief was obtained but eventually subsided. Amitriptyline 10 mg daily at bedtime was added to the current regimen and titrated to 75 mg daily. Hydromorphone 2 mg every 4 hours as needed for breakthrough pain was added. CL continued to complain of severe neuropathic pain. A baseline EKG revealed a QTc of 428. Methadone was initiated at 2.5 mg 3 times a day and docusate and senna were prescribed to prevent opioid-induced constipation. CL reported pain relief and significant improvement in functional status. Numerous counseling sessions were held with the patient to discuss toxicities and drug—drug interaction potential of her pain regimen. PTHS
Alex Ganetsky, PharmD, is a hematology/oncology clinical pharmacy specialist at the Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania.
www.PharmacyTimes.com Pharmacy Times HS | 01.12 n 11 For a list of references for the pediatric and oncology case studies and a figure, go to www.PharmacyTimes.com/ publications/issue/2012/January2012. › Web .com An estimated 12% of children younger than 11 years of age take acetaminophen in any given week.