Volume 27, Number 11 December 2013 MEDICATION SAFETY FORMULARY UPDATE The Pharmacy and Therapeutics Re-dosing of reversal agents in Committee met November 19, 2013. 3 drugs were added in the Formulary, the inpatient setting 1 product was deleted, 5 drugs were designated non-formulary and not ntidotes and reversal agents play a minutes to work when administered via available, 1 product was designated Acritical role in both intentional and these alternative routes. The initial dose high-priority non-formulary, and 1 unintentional medication overdose. The of naloxone for adults is 0.04-0.4 mg. If therapeutic interchange was approved. ideal antidote or reversal agent would there is no response, the dose should completely counteract the uninten- then be repeated every two to three tional consequences of medication minutes. Doses should be initiated low ◆ ADDED overdose. In a perfect world, this would with increases until an adequate level Diphtheria, Tetanus Toxoid, and be achieved via a single dosage of the of alertness is achieved. If no response Acellular Pertussis, Hepatitis B, antidote. However; this is often not is observed after 10 mg, the respiratory depression is likely not due to opioid in- and Inactivated Poliovirus the case. A number of agents require intense monitoring post-administration toxication.[3] After naloxone administra- (Pediarix®) (vital signs, laboratory values, etc.) with tion, monitor for a reduction in opioid ef- Hydroxyethyl Starch 6% Solution potential re-administration necessary fects in regards to blood pressure, heart (Voluven®)* to treat continued adverse effects. This rate, and respiratory rate. Naloxone may *Restricted to submucosal injections article serves to summarize common also precipitate signs and symptoms of during endoscopic resection. antidote and reversal agents utilized at opioid withdrawal such as: abdominal UF Health Shands Hospital. cramps, shaking, chills, nausea, vomit- Poractant alfa (Curosurf®) Opioid analgesia is considered a rela- ing, and diarrhea.[3] ◆ DELETED tively safe treatment option for patients, Benzodiazepines (BZDs) are widely although sometimes associated with ad- prescribed for anxiety in the outpatient Calfactant (Infasurf®) verse events, the most serious of which setting, but are also used for other indi- is respiratory arrest. The risk of adverse ◆ NON-FORMULARY AND cations while patients are in the hospi- consequences of therapy increases tal. Flumazenil is a competitive inhibitor NOT AVAILABLE with higher opioid doses, the morbidly of the gamma aminobutyric acid (GABA) Bupivacaine Liposomal (Exparel®) obese, pediatric and geriatric popula- receptor (BZD binding site) and is used tions, critically ill patients, and also to reverse benzodiazepine-related seda- ® Calfactant (Infasurf ) those who receive concurrent central tion. The classic presentation of BZD Etidronate (generic) nervous and respiratory depressants overdose manifests as CNS depression (such as anxiolytics and sedatives).[1] At with slurred speech, ataxia, and altered Insulin Lispro (Humapen® the bedside, the most easily recogniz- mental status with more severe toxici- LuxuraTM) able sign of opioid overdose is a decline ties resulting in lethargy or coma.[5] The in respiratory rate. A rate of 12 breaths recommended dose for sedation reversal Vortioxetine (Brintellix®) per minute or less strongly suggests is 0.2 mg given IV over 30 seconds. ◆ HIGH-PRIORITY an opioid intoxication, predominantly Repeated doses of 0.2 mg up to a maxi- NON-FORMULARY when the patient is lethargic as well. mum single dose of 1 mg administered [2] Naloxone, an antidote for opioid over 30 seconds may be given at one ® Insulin Glulisine (Apidra )* intoxication, is a competitive mu opioid- minute intervals until the desired effect *Restricted to use in insulin pump only. receptor antagonist which causes a is achieved, with no more than 3 mg of ◆ THERAPEUTIC INTERCHANGES reversal of all signs and symptoms of flumazenil given within one hour.[6] The opioid intoxication. The onset of action reversal of BZD toxicity occurs rapidly, Vitamin B Complex Tablet§ of IV naloxone is less than two min- approximately 6-10 minutes after IV ad- §Interchanged to individual ingredients: thiamine 50 mg, niacin 50 mg, cyano utes and has a duration of action of 20 ministration. As with naloxone, the du- cobalamin 50 mcg, and pyridoxine to 90 minutes (a much shorter period ration of the flumazenil is much shorter 50 mg of action than that of many opioids). than many of the agents it is reversing. Common opioid elimination half-lives Many benzodiazepine elimination half- are listed in Table 1. Doses may also be lives are listed in Table 1. In the event administered intramuscularly, subcuta- of re-sedation, repeated doses may be (continued on next page) neously, or orally, but may take up to 15 (continued on page 5) Formulary update, from page 1 animal studies and 1 small human study Initial concerns with a switch to showing extended duration of “lift” when poractant included the need to Diphtheria, Tetanus Toxoid, and HES is used in comparison to normal maintain calfactant in the Formulary Acellular Pertussis, Hepatitis B, and saline. The data concluded that HES was for treatment of meconium aspiration Inactivated Poliovirus (Pediarix®) superior to NS in the provision of an in full term infants (no surfactant combination vaccine is indicated for elevated time of mucosal cushion after product currently carries FDA approv- patients at least 6 weeks of age to 6 injection in patients with lesions > 3 cm. al for this indication). However, a years of age born to HBsAg negative The use of this agent was not study published in China indicated the mothers. The CDC currently recom- requested as a wholesale conversion, safety and efficacy of poractant use in mends vaccination for Hepatitis B, but rather for use in patients with full term babies for this indication. The DTaP, Hib, PPSV 23 and IPV at 2, 4, lesions greater than 2 cm, with early neonatal physician group has indi- and 6 months of age. cancer or high-grade dysplasia (approxi- cated approval to use poractant in the In infants who are born premature- mately 5 patients per month with full term babies which would elimi- ly, it is possible that they would expected growth as program expands). nate the need to maintain two receive their 2, 4 and 6 month At the current rate, this switch will be products in the Formulary. vaccinations while in the hospital. effectively cost-neutral. The P&T The Committee recommended that This would require 3 needle sticks approved addition of this product in the poractant be added in the Formulary secondary to lack of a combination and calfactant be removed and be vaccine available in the Formulary. Formulary with a restriction to submu- designated non-formulary and not Historically, UF Health has carried cosal injection. Intravenous administra- available. In addition, the Committee only single entity vaccines due to the tion of this agent will not be allowed. ® recommended that calfactant be wide availability of vaccinations in Poractant alfa (Curosurf ) was FDA retrospectively reviewed for incidence the outpatient setting. approved in November of 1999 for the of ET tube occlusion and/or airway Evaluation of current practices treatment (rescue) of respiratory occlusion. Poractant would be indicated a potential for decreased distress syndrome (RDS) in premature evaluated for these same adverse needle sticks in infants who remain infants. It is an extract of natural outcomes at a 6 month time period. hospitalized for prolonged periods of porcine lung surfactant which consists time. A cost evaluation was per- of 99% polar lipids and 1% hydrophobic Bupivacaine Liposomal Injection ® formed which yielded annual low molecular weight proteins (surfac- (Exparel ) was approved by the FDA cost-avoidance with conversion to the tant associated proteins SP-B and SP-C). in October 2011 for single-dose combination vaccination secondary to This agent was requested for addition infiltration into the surgical site prior potential elimination of poliovirus in the Formulary secondary to the to bunionectomy or hemorrhoidectomy vaccine waste. The Committee voted supposition that this agent results in a to produce post-surgical anesthesia. In to add Pediarix® in the Formulary lower incidence of endotracheal tube January 2012, the P&T Committee while retaining the single-component (ET tube) reflux than our current designated bupivacaine liposomal vaccines for use in patients not surfactant product, calfactant. injection non-formulary and not requiring the combination series. Administration of any surfactant available. The Committee stipulated Hydroxyethyl Starch 6% (Voluven®) carries a risk of ET tube occlusion and that this product could be re-evaluated was designated non-formulary and reflux as well as complete airway if published literature provided not available in August 2013. The obstruction. Product labeling for sufficient evidence that it would be Pharmacy and Therapeutics Commit- calfactant indicates it has a 23% cost-effective in the inpatient setting. tee removed all hydroxyethyl starch incidence of ET tube occlusion/reflux In August 2013, liposomal bupivacaine (HES) products at that time second- versus no listed incidence with porac- was evaluated at the request ary to a June 2013, FDA-issued tant alfa. An open label comparison of of The Department of Surgery for MedWatch. This MedWatch noted poractant to calfactant boasts a statisti- use in hemorrhoidectomy and that intravenous HES should not be cally significant difference in ET tube rectal surgeries. used in critically ill adults secondary occlusion rates (3.5% vs. 13.2% respec- Bupivacaine liposomal injectable to increased risk of morbidity, tively, p< 0.001). It has been proposed suspension is an extended-release including bleeding and renal injury, that administration of calfactant as a formulation of bupivacaine. It works as well as mortality. Since that time continuous infusion via syringe pump as a local anesthetic whereby upon period, the use of 6% HES for may lessen the incidence of reflux into injection, bupivacaine is released from submucosal injection during endo- the ET tube.