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Home , Prochlorperazine

Volume 23, Number 6 June 2009 Drugs & Therapy B N U N L N L N E N T N I N N

MEDICATION SAFETY FORMULARY UPDATE The Pharmacy and Therapeutics Prochlorperazine — Committee met May 19, 2009. No drugs were added in the Formulary while 1 was deleted. 9 drugs or dos- the forgotten age forms were designated nonfor- mulary and not available. Criteria ata from 2006 attributed 3.7% of and to reduce narcotic requirement in were changed for 6 drugs, including D Emergency Department (ED) visits some surgical situations. 2 exceptions to “contraindications.” to and vomiting, which was the Although like pro- 4th most common reason for an ED visit. chlorperazine and are Nausea and/or vomiting are the result in the same general pharmacologic ◆ ADDED of peripheral or central stimulation of class, they do not have identical pri- None the chemoreceptor trigger zone (CTZ). mary mechanism of actions or adverse Precipitating factors include ingestion events. Prochlorperazine blocks post- of medications or toxins, infection, gas- synaptic mesolimbic D1- ◆ DELETED - trointestinal obstruction, gastroparesis, and D2 receptors, which includes the Lomustine (CeeNu® Dosepack)* , , and surgical CTZ, explaining its antiemetic effect. *Nonformulary and must be ordered procedures. Treatment options are usu- Prochlorperazine also has moderate on Order Form ally described as 2 broad categories: anticholinergic and alpha-adrenergic and prokinetics. Antiemet- -blocking activity. Prometha- ◆ NONFORMULARY AND ics include phenothiazines, antihis- zine is primarily a competitive hista- NOT AVAILABLE tamines, anticholinergics, mine1-receptor blocker with muscarinic antagonists, and 5-HT3 antagonists. M1-receptor-blocking activity resulting Darifenacin Prokinetic agents used for dysmotility in antihistaminic, , anti-mo- (Enablex® by Novartis)† syndromes include tion-sickness, antiemetic, and anticho- Fesoterodine (Toviaz® by Pfizer)† and erythromycin. linergic properties. Phenothiazines, specifically prochlor- Despite proven efficacy, these medi- Flavoxate (Generic)† and promethazine, are often cations are not without risks. As recent Oxybutynin ER overlooked with the presence of newer, as March 2009, promethazine was the (Ditropan® XL by Ortho)† more heavily promoted antiemetic center of a US Supreme Court decision agents like 5-HT3 antagonists (eg, about product liability. In 2000, a musi- Oxybutynin Transdermal ). However, these agents cian went to the emergency room for ® (Oxytrol by WatsonPharma)‡ should not be disregarded. The 5-HT3 a with nausea. She received ‡Prescriber must change to tolterodine antagonists are used mainly for preven- meperidine and promethazine intra- ER or oxybutynin IR tion of nausea. Clinical experience sug- venously (IV). At the site of infusion, gests that 5-HT antagonists are not as she developed gangrene that required Solifenacin 3 effective once a patient is vomiting. amputation of the forearm.1 Intrave- (Vesicare® by GlaxoSmithKline)† Promethazine was developed in the nous preparations of pro­methazine Tolterodine IR (Detrol® by Pfizer)† 1930s, followed by prochlorperazine have a pH between 4 and 5.5. At this in the 1950s. Initially developed for pH, the surrounding tissue can become Trospium IR/ER anesthesia and use, severely damaged if extravasation from (Sanctura®/XR by Allergan)† these agents were later found to have the IV site occurs. We have previously †Interchanged to tolterodine ER antiemetic effects. Over time, anti- cautioned about this potential problem emetic use became their principal place in the Bulletin. Also, cautionary alerts ◆ INTERCHANGES in therapy. Not only are phenothiazines warning nurses to dilute the vial into effective, there are multiple dosage (continued on page 6) Tolterodine ER (Detrol® LA) for forms available, from oral formulations Darifenacin (Enablex®) to suppositories and parenteral routes. Tolterodine ER (Detrol® LA) for Prochlorperazine has labeled indica- ◆ Fesoterodine (Toviaz®) tions for the control of severe nausea INSIDE THIS ISSUE and vomiting as well as treatment of Tolterodine ER (Detrol® LA) for . Promethazine is labeled ◆ Flavoxate (Generic) Use Cockcroft-Gault for renal dosing for the treatment of active motion sick- ness, prevention of postoperative nau- ◆ Ceftriaxone + calcium (continued on next page) sea and vomiting, allergic reactions, ◆ CRITERIA-FOR-USE CHANGES (cont.)

Formulary update, from page 1 THERAPEUTIC INTERCHANGE OF OAB AGENTS Interchanged to Tolterodine ER 2 mg daily ◆ INTERCHANGES (cont.) Tolterodine IR 1 mg twice a day Oxybutynin ER 5 mg daily Darifenacin 7.5 mg daily Solifenacin 5 mg daily Tolterodine ER (Detrol® LA) for Trospium IR 20 mg daily Flavoxate 100 mg 3-4 times/day Oxybutynin ER (Ditropan® XL) Tolterodine ER (Detrol® LA) for Interchanged to Tolterodine ER 4 mg daily Solifenacin (Vesicare®) Tolterodine IR 2 mg twice a day Oxybutynin ER 10-30 mg daily Darifenacin 15 mg daily Solifenacin 10 mg daily Tolterodine ER (Detrol® LA) for Trospium IR 20 mg twice a day Trospium ER 60 mg daily Tolterodine IR (Detrol®) Flavoxate 200 mg 3-4 times/day Fesoterodine 4-8 mg daily Tolterodine ER (Detrol® LA) for ® OAB may affect quality of life for some the stimulation of clotting factors (ie, fac- Trospium ER (Sanctura XR) patients and is characterized by symp- tor VIII and von Willebrand factor [vWF]). Tolterodine ER (Detrol® LA) for toms of frequency and urgency, with or DDAVP has labeled indications for Trospium IR (Sanctura®) without urge incontinence. Antimusca- diabetes insipidus, enuresis, and rinic agents are first-line pharmacological bleeding in patients with hemophilia ◆ CRITERIA-FOR-USE CHANGES options for OAB. There are 6 marketed or von Willebrand’s disease. It is used antimuscarinic drugs with labeled indi- off-label for various uses including ure- Desmopressin Injection (DDAVP cations for the treatment of OAB. Flavox- mic bleeding. Patients with advanced [Generic])§ ate is used off-label for OAB. kidney disease are predisposed to §Use for uremic bleeding permitted There is no consensus on the preferred bleeding because of platelet dysfunc- agent for the treatment of OAB. Oxybu- tion. DDAVP improves platelet func- ® (Tikosyn by Pfizer)¶ tynin IR tablets and syrup and tolterodine tion, presumably because it stimulates ¶Dofetilide Order Form required ER capsules have been listed in the For- vWF. Everolimus mulary. Over the past year, there has been According to the official labeling, (Afinitor® by Novartis)** little use of the other agents in this class. DDAVP use is contraindicated in The comparative efficacy and safety of patients with a creatinine clearance **Chemotherapy Order Form required the various antimuscarinic agents used less than 50 mL/min. The clearance of Heparin, Unfractionated for OAB have been evaluated in system- DDAVP is reduced, which may cause (Generic)†† atic reviews and meta-analyses. The an unexpected degree of water ac- most recent and comprehensive of these cumulation leading to hyponatremia. ††Saline used to flush central catheters reviews show no significant difference However, there are instances in which in efficacy among the antimuscarinic it may be appropriate to use DDAVP in Linezolid (Zyvox® by Pfizer)‡‡ agents for OAB. ER products may be pre- patients with kidney disease. ‡‡Use with sympathomimetics per- ferred over IR products in patients who Uremic bleeding typically presents mitted in monitored units; Progress experience adverse reactions (ADRs). In with ecchymoses, purpura, epistaxis, Note required for use with antide- clinical trials, patients treated with tolt- and bleeding from venipuncture pressants erodine ER rarely discontinued therapy sites. These patients can also present Oseltamivir because of ADRs. with gastrointestinal or intracranial (Tamiflu® by Roche)§§ Detrol® LA is the most commonly bleeding. Because DDAVP normalizes prescribed drug used to treat OAB. It bleeding time in 75% of patients with §§Restricted to ID physician approval is the 66th most common prescription chronic renal failure, it is the most in community pharmacies (ie, 5.6 mil- common agent used in active uremic Lomustine is an oral alkylating lion prescriptions). Tolterodine ER was bleeding. DDAVP doses for uremic agent marketed since 1976 that is selected to represent OAB drugs so that bleeding are approximately 10-fold used to treat Hodgkin’s disease and the fewest number of interchanges will higher than doses used for diabetes brain tumors. The CeeNU® Dose-Pack, be necessary. insipidus (0.3 mcg/kg to 0.4 mcg/kg which contained 10-, 40-, and 100-mg Oxybutynin IR tablet and syrup remain IV or SQ as a single injection). An capsules, is no longer available. Only in the Formulary for patients taking it as important advantage of DDAVP is its the individual capsule strengths are a home medication and for patients un- rapid onset of action for acute bleeding available. able to take oral solid dosage forms. caused by uremic platelet dysfunction. Lomustine has not been used at Desmopressin is a synthetic analog Studies have shown that DDAVP Shands at UF for several years. There- of the endogenous hormone arginine decreases bleeding time within an fore, it was deleted from the Formu- vasopressin, which is often referred to hour after injection. Alternative op- lary. If ordered nonformulary, it still as DDAVP. DDAVP® is a brand name, but tions (eg, cryoprecipitate; erythro- must be ordered on a Chemotherapy it is also an acronym for 1-deamino-8-d- poietin) take hours to weeks to show Order Form. arginine vasopressin. Natural vasopressin effects. DDAVP has a short duration of Darifenacin, fesoterodine, flavoxate, is also called antidiuretic hormone (ADH), activity; bleeding time returns to base- oxybutynin extended-release (ER), which is secreted by the hypothalamus in line within 24 hours. Disadvantages of oxybutynin transdermal, solifenacin, response to various physiologic stimuli. DDAVP include reported tachyphylaxis tolterodine immediate-release (IR), For example, hyperosmolality and volume after 1 dose, headache, facial flushing, and trospium IR/ER are antimuscarinic depletion stimulates ADH release, which and rare thrombotic events. drugs used for symptoms of overactive causes the normal kidney to reabsorb Despite the labeled contraindication, bladder syndrome (OAB). These agents water from the renal tubules and adjusts the P&T Committee determined that were designated nonformulary and serum osmolality and fluid balance. During DDAVP is a reasonable option to treat not available and will be interchanged severe hemorrhage, large quantities of uremic bleeding, even though these to an equivalent dosage of tolterodine ADH are secreted for its pressor effect. Like patients have a creatinine clearance ER based on the table (see top of next many endogenous hormones, ADH has less than 50 mL/minute. column). various other physiologic effects, including (continued on next page) 2 Formulary update, from page 2 mendation is based on insufficient evi- a list of options (monitor for signs/ Dofetilide is a class III antiar- dence to support the use of heparin and symptoms of syndrome; rhythmic used for the conversion and risks associated with heparin use (ie, risk consider an alternative antibiotic; or maintenance of normal sinus rhythm in of heparin-induced thrombocytopenia discontinue the ). patients with atrial fibrillation/flutter. [HIT] and inadvertent heparin systemic It may not be possible to discontinue Because of its risks, it is reserved for anticoagulation [including possible over- either of the interacting agents (eg, highly symptomatic patients. doses]). linezolid or SSRI) safely. The progress Drugs that inhibit dofetilide metabo- Recent benchmarking showed that note will serve as a reminder to pre- lism or renal elimination may increase many institutions use saline to flush cen- scribers to keep serotonin syndrome in the risk of dofetilide-induced proar- tral venous lines (CVLs). Manufacturer their differential diagnosis when treat- rhythmias. In addition, concomitant information for the central venous cath- ing patients’ symptoms. Even if the use of dofetilide with drugs associated eters used at Shands at UF recommends SSRI is stopped, drug persists in the with QT prolongation or torsade de the use of saline or “local practice” and body and a reaction may be possible. pointes is contraindicated. To minimize cites the Intravenous Nursing Society Since the interaction with pressors the risk of induced arrhythmia, patients (INS) standards. Therefore, the P&T results in an elevated blood pressure initiated or re-initiated on dofetilide Committee endorsed the use of saline and patients will be monitored in criti- must stay a minimum of 3 days in a instead of heparinized saline to maintain cal care settings, this is an exception facility that can provide calculations the patency of temporary central venous to the contraindication. Thus, linezolid of creatinine clearance, continuous catheters in adults. and pressors can be used together in electrocardiographic (ECG) monitoring, Linezolid is a unique antibiotic used monitored units. and cardiac resuscitation. Dofetilide is primarily to treat resistant enterococ- should always be available only to hospitals and prescrib- cal infections and methicillin-resistant stopped when a patient is on linezolid. ers who have received appropriate Staphylo­coccus aureus (MRSA) infections , which is used to treat hypo- dofetilide dosing and treatment initia- in patients that are either intolerant or tension, may be used with linezolid, tion education. refractory to vancomycin therapy. Use of since the purpose of midodrine is to Because of these limitations, errors of this agent has increased as the number increase blood pressure and patients omission upon admission to the hospital of resistant gram-positive infections are monitored. must be considered. It may be unaccept- has increased. Linezolid is a “last-line” Oseltamivir is a neuraminidase able to stop dofetilide during a patient’s antibiotic for resistant gram-posi­tive inhibitor with a labeled indication for admission (for a non-cardiac reason) to infections. the treatment of uncomplicated acute avoid these interactions and possible The concomitant use of linezolid and illness due to influenza infection in risks. Do not stop dofetilide without selective serotonin reuptake inhibitors patients 1 year of age and older who consulting the patient’s cardiologist. (SSRIs) or sympathomimetic agents are have been symptomatic for no more In order to use dofetilide, patients frequent contraindicated drug-drug inter- than 2 days. Because of its activity must be followed by a cardiologist action alerts generated by the pharma- against type A influenza viruses, it is registered in the restricted-distribution cy’s computer system. According to the a drug of choice for the treatment of program. Therefore, the dofetilide poli- product labeling, linezolid is contraindi- the current H1N1 virus that is caus- cy was revised to include a pre-printed cated in patients taking SSRIs, ing swine-originated influenza (or the Dofetilide Order Form for patients , , meperidine, or “swine flu”). continuing home therapy on non-cardi- (unless carefully observed for Effective May 8, 2009, the P&T ology services. This order set contains signs and/or symptoms of serotonin syn- restricted the use of oseltamivir to an automatic order for a Cardiology drome). Linezolid is also contraindicated patients that have been approved for Consult to ensure appropriate manage- in patients taking directly and indirectly inpatient use by an infectious diseases ment of patients who may otherwise acting sympathomimetic agents (eg, physician. This action was recommend- not be monitored. The patient’s chart pseudoephedrine), vasopressive agents, ed by the Resistant Pathogen Task must include an order for this service. or dopaminergic agents (unless moni- Force near the beginning of the swine Everolimus is a kinase inhibitor with tored for potential increases in blood flu outbreak. The goal is to ration sup- a labeled indication for the treatment pressure). plies so that drug is available for the of advanced renal cell carcinoma after A P&T Committee-authorized neediest patients (see table below). failure of treatment with sunitinib or Linezolid Progress Note was approved, These criteria are not absolute, and sorafenib. Neither sunitinib (Stutent®), which will be placed in a patient’s ID physicians will use their discretion nor sorafenib (Nexavar®) are listed in chart when they are on linezolid and at determining “high risk.” When this the Formulary. Everolimus is pharma- an antidepressant. The progress note restriction will end will be determined cologically different from sunitinib or reminds the prescribers of the “contra- by whether the swine flu epidemic per- sorafenib because it inhibits a specific indicated” combination and provides sists throughout the summer months. kinase inhibitor, mammalian target of rapamycin (mTOR). CRITERIA FOR OSELTAMIVIR USE IN HOSPITALIZED PATIENTS [ONLY] Everolimus was not added in the Formulary, but it was added in the n Patients with a confirmed case of n Acute febrile respiratory illness Chemotherapy Policy. If prescribed for swine-originated influenza virus within 7 days of travel where an inpatient, the order must be written (S-OIV) there are 1 or more confirmed cases of S-OIV on a Chemotherapy Order Form. n Patients with a probable case of n Patients with acute febrile respi- Unfractionated heparin and saline S-OIV n ratory illness and who are at high are used to maintain the patency of Acute febrile respiratory illness risk of complications who is Influenza A positive (ie, “flush”) intravenous catheters. n n Immunocompromised patients The Nursing Department’s Clinical and Patients with a suspected case of S-OIV n Pregnant females Evidenced-Based Council requested n Acute febrile respiratory illness n Patients < 5 yrs or > 65 yrs of age that the P&T Committee endorse a within 7 days of close contact with n Patients with chronic respiratory change from heparin to saline for the a confirmed or probable case of and cardiopulmonary conditions flushing of temporary central venous S-OIV catheters in adult patients. This recom- 3

POLICIES AND PROCEDURES "Cockcroft-Gault for drug dosing… not MDRD" here has been a debate about whether the Modified T Diet in Renal Disease (MDRD) method of estimating glomerular filtration rate (eGFR) or the Cockcroft-Gault (C-G) method of estimating creatinine clearance (CrCl) should be used to guide drug dosing in patients with impaired renal function. A recent study showed that the MDRD method of estimating renal function could result in subtherapeutic drug dosing in patients with stage IV or V kidney disease and supratherapeutic drug dosing in patients with stage III disease (assuming the C-G method provides the “correct” dosage).1 Both C-G and MDRD are estimates of renal function. A creatinine clearance may need to be measured when pa- tients have characteristics that make the C-G unreliable. For example, the C-G equation (see box below) relies on the patient's serum creatinine value to estimate creatinine ◆ The National Kidney Disease Education Program (NKDEP) does not recommend the use of MDRD for drug dosing in patients with renal impairment.

clearance. When a patient's creatinine production is atypi- cal (patients with disease, patients who are cachec- tic), the C-G equation may overestimate a patient's renal function. A patient may receive too much drug based on an overestimate of their creatinine clearance. Regardless of the method of estimating creatinine clearance, it may be necessary to measure the patient's renal function or drug levels when the risk of an overdose is high.

COCKCROFT-GAULT EQUATION*†‡

Estimated Creatinine Clearance (mL/min) = [140 – Age (yr) x weight (Kg)][72 x Serum Creatinine (SCr)]

*Multiply by 0.85 for females †Use Ideal Body Weight (kg) = men = 50 kg + (2.3 kg x inches greater than 5 ft); women = 45.5 kg + (2.3 kg x inches greater than 5 ft) ‡Normalize for BSA (1.73 m2)

The National Kidney Disease Education Program (NKDEP) does not recommend the use of MDRD for drug dosing in patients with renal impairment.2 Current dos- ing recommendations were based on the C-G method of adjusting dosing. Therefore, the P&T Committee endorsed the NKDEP position on using Cockcroft-Gault versus MDRD for drug dosing in patients in impaired renal func- tion. MDRD remains the preferred method of estimating a patient’s renal function and identifying patients with kidney disease. Shands already complies with the NKDEP recommendation that laboratory creatinine values be standardized with calibration traceable to isotope dilution mass spectrometry (IDMS). REFERENCES 1. Moranville MP, Jennings HR. Implications of using modification of diet in renal disease versus Cockcroft-Gault equations for renal dosing adjustments. Am J Health-Syst Pharm 2009;66:154-61. 2. Anon. Creatinine standardization recommendations. National Kidney Disease Education 4 Program. Accessed May 25, 2009 at http://www.nkdep.nih.gov/labprofessionals/Pharma- 4 cists_and_Authorized_Drug_Prescribers.htm.

MEDICATION SAFETY Ceftriaxone-calcium update eftriaxone is an injectable third-generation cephalo- C sporin with activity against gram-positive and gram- neg­ative bacteria. Its penetration into the central nervous system has made it a valuable agent in the treatment of men­ingitis. Its long half-life allows for once-daily dosing. In December 2007, the criteria for ceftriaxone use at Shands at UF were reviewed based on changes to the product’s labeling, which included a contraindication for the co-administration of ceftriaxone and calcium-contain- ing intravenous solu­tions, including parenteral nutrient preparations, in neonates age 28 days or younger. Ceftri- axone was already contraindicated in hyperbilirubinemic newborn infants. Warnings were added in the labeling stating that ceftriaxone should not be mixed or administered simul­ taneously with calcium-containing solutions or products, even via differ­ent infusion lines, and that calcium-con- taining solutions or products must not be administered within 48 hours of the last administration of ceftriax­one. These warning were based on 5 neonatal deaths reported between 1992 and 2002 by post-marketing surveillance where there was an association between ceftriaxone and calcium-containing products and crystalline material found in the kid­ney and lungs upon autopsy. ◆ On April 14, 2009, the FDA modified ceftriaxone’s labeling, and the labeling is now consistent with the restrictions approved by the Shands P&T Committee in 2007.

In 2007, the P&T Committee found no conclusive evi- dence to support a significant safety risk of ceftriaxone in non-neonates; therefore, ceftriax­one use in children 28 days old or younger was prohibited based on the contra- indication language in the labeling. Use in children older than 28 days old and adults was not restricted. On April 14, 2009, the FDA once again modified ceftri- axone’s labeling, and the labeling is now consistent with the restrictions approved by the Shands P&T Committee in 2007.1 The contraindication in children less than or equal to 28 days of age with intravenous calcium contain- ing products remains. Patients older than 28 days old may receive these products sequentially provided the infusion lines are flushed thoroughly. The FDA no longer consid- ers administration of calcium-containing products and ceftriaxone contraindicated for 48 hours of the last dose of ceftriaxone. These changes were based on 2 in vitro studies using neonatal and adult plasma. Ceftriaxone still should not be mixed with calcium in the same IV or by Y-site administration, regardless of the patient's age. REFERENCES 1. Anon. Information for healthcare professionals: ceftriaxone [4/21/09 Update}. Accessed online on May 25, 2009 at http://www.fda.gov/cder/drug/InfoSheets/HCP/ ceftriaxone042009HCP.htm.

5 5 Drugs & Therapy SHANDS NON-PROFIT ORG. B N U N L N L N E N T N I N N Shands at the University of Florida U.S. POSTAGE DRUG INFORMATION SERVICE PAID GAINESVILLE, FL Volume 23, No. 6 June 2009 PO Box 100316 PERMIT NO. 94 This publication is produced by the Gainesville, FL 32610-0316 Drug Information and Pharmacy Re- source Center under the direction of the Department of Pharmacy Services and the Pharmacy and Therapeutics Committee. EDITOR, DRUGS & THERAPY BULLETIN Randy C. Hatton, PharmD DIRECTOR, PHARMACY SERVICES Alan Knudsen, MS, RPh CHAIRMAN, PHARMACY & THERAPEUTICS COMMITTEE Ricardo Gonzalez-Rothi, MD EDITING, DESIGN, & PRODUCTION Shands HealthCare’s Publication Svcs. © Copyright 2009. All rights reserved. No portion of the Drugs & Therapy Bulletin may be reproduced without the written consent of its editor. FOR MORE INFORMATION, VISIT US ONLINE http://shands.org/professionals/ druginfo/bulletin.asp

Medication safety, from page 1 children less than 2 years of age and promethazine in uncomplicated nausea a volume of 10 mL of normal saline advising caution to be used in children and vomiting found prochlorperazine before adminis­tration of IV prometha- 2 years and above due to a potential was superior at 30 and 60 minutes. Ad- zine have been added to dispensing risk for fatal respiratory depression. ditionally, the prochlorperazine group cabinets. Some hospitals have consid- Prochlorperazine carries a similar had fewer treatment failures and com- ered totally removing promethazine contraindication to its use in children plaints of drowsiness. There was no from their formularies. 2 years of age or younger or less than difference in the frequency of Many institutions stopped using 20 pounds. Both promethazine and between the 2 groups.4 prochlorperazine and switched to prochlorperazine also carry a risk of Providers have many options for promethazine during a prochlorpera- ; therefore, the lowest the treatment of nausea and vomiting. zine shortage in 2001 (which has since effective dose and caution should be Prochlorperazine should be considered resolved). Unfortunately, an increase used in patients with cardiovascular as an early option for nausea and vomit- in adverse events was associated with issues. Long-term use or high doses of ing since it has established efficacy and the change.2 The promethazine product any may result in akathi- it can be given by multiple routes of labeling states that the preferred route sia and . administration. When IV administration of parenteral administration is a deep The Institution of Safe Medical Prac- is necessary, prochlorperazine has the IM injection; however, IV is frequently tices (ISMP) includes promethazine IV advantage of having limited, relatively used. The IM route is preferred to the in its list of high-alert medications and minor infusion-related reactions. Sug- IV because promethazine is a known has recommended multiple strategies gested equivalent parenteral (IV/IM) vesicant. If administered intra-arterially, to prevent or reduce tissue damage doses of prochlorperazine for prometha- promethazine can cause gangrene, as when promethazine is administered IV. zine are 5 to 10 mg of prochlorpera- in the previous case, and subcutane- Some of these practice recommenda- zine for 6.25-12.5 mg and 25-50 mg of ous administration may cause tissue tions are to limit the dose, use a large promethazine, respectively. This can necrosis. Other injuries reported include patent vein, and educate the patients be repeated every 3 to 4 hours with a burning, erythema, severe spasm of ves- to alert the provider immediately of maximum daily dose of 40 mg. sels, thrombophlebitis, venous thrombo- any burning or pain with the infusion. By Julia Logan, PharmD sis, phlebitis, nerve damage, paralysis, Prochlorperazine does not carry these REFERENCES abscess, and tenderness at the injection warnings, although there is evidence 1. Wyeth v. Levine, 129 S. Ct. 1187, (March 4, 2009). site. Prochlorperazine infusion has less that administration as an IV infusion, 2. Sheth HS, Verrico MM, Skledar SJ, et al. Promethazine���������������� ad- verse events after implementation of a medication shortage severe infusion-related reactions but is rather than as a bolus, has a lower interchange. Ann Pharmacother 2005;39:255-61. associated with hypotension and akathi- incidence of akathisia. 3. Collins RW, Jones JB, Walthall JD, et al. Intravenous administration of prochlorperazine by 15-Minute bolus does sia if administered as a bolus. These phenothiazines are not often not affect the incidence of akasthisia: a prospective, random- In addition to warnings about admin- compared, but a randomized, double- ized, controlled trial. Ann Emerg Med 2001;38:491-4. 4. Ernst AA, Weiss SJ, Park S, et al. Prochlorperazine versus istration, promethazine has a black-box blind comparing time to promethazine for uncomplicated nausea and vomiting in the 6 warning contraindicating its use in relief for IV prochlorperazine and IV emergency department: a randomized, double-blind clinical trial. Ann Emerg Med 2002;32:89-94.