Generic Name: Ceftaroline Fosamil
Class: Fifth Generation Cephalosporins
VA Class: AM119
Chemical Name: 4 - [2 - [[(6R,7R) - 2 - Carboxy - 7 - [[(2Z) - (ethoxyimino)[5 - (phosphonoamino) - 1,2,4 - thiadiazol - 3 - yl]acetyl]amino] - 8 - oxo - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - en - 3 - yl]thio] - 4 - thiazolyl] - 1 - methyl - pyridinium, inner salt, monoacetate, monohydrate
Molecular Formula: C22H21N8O8PS4.C2H4O2.H2O
CAS Number: 866021-48-9

Introduction

Antibacterial; β-lactam antibiotic;1 5 6 7 fifth generation cephalosporin.5 6 7 8 27

Uses for Teflaro

Community-acquired Pneumonia

Treatment of community-acquired bacterial pneumonia (CABP, CAP) caused by susceptible Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only), Haemophilus influenzae, Klebsiella pneumoniae, K. oxytoca, or Escherichia coli.1 3

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Skin and Skin Structure Infections

Treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible S. aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus, ORSA], S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), E. coli, K. pneumoniae, or K. oxytoca.1 2

Teflaro Dosage and Administration

Administration

Administer by IV infusion.1

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Do not admix with or add to solutions containing other drugs.1

Reconstitution and Dilution

Reconstitute 400- or 600-mg single-use vials of ceftaroline fosamil by adding 20 mL of sterile water for injection, 0.9% sodium chloride, 5% dextrose, or lactated Ringer's injection to provide solution containing approximately 20 or 30 mg/mL, respectively.1 Mix vial gently to ensure complete dissolution;1 reconstitution should take <2 minutes.1

Dilute appropriate dose of reconstituted solution in 50–250 mL of the same diluent used for reconstitution, unless drug was reconstituted with sterile water, in which case any compatible IV infusion solution (see Solution Compatibility under Stability) should be used for further dilution.1 When using a 50-mL infusion bag, remove 20 mL of diluent from bag prior to injecting entire reconstituted contents of 400- or 600-mg vial, to provide infusion solution containing approximately 8 or 12 mg/mL, respectively.1

Reconstituted and diluted solutions appear clear and light to dark yellow.1

Final solution in IV infusion bag should be used within 6 hours when stored at room temperature or within 24 hours when stored in refrigerator at 2–8°C.1

Rate of Administration

Administer by IV infusion over approximately 1 hour.1

Dosage

Available as ceftaroline fosamil monoacetate monohydrate; dosage expressed in terms of anhydrous ceftaroline fosamil.1

Adults

Community-acquired Pneumonia
IV

600 mg every 12 hours for 5–7 days.1

Duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.1

Skin and Skin Structure Infections
IV

600 mg every 12 hours for 5–14 days.1

Duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.1

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations;1 hepatic impairment not expected to have a clinically important effect on systemic clearance of the drug.1

Renal Impairment

Adjust dosage in adults with Clcr ≤50 mL/minute, including those undergoing hemodialysis.1 (See Table 1.)

Table 1. Dosage for Adults with Renal Impairment1

Clcr (mL/min)

Recommended Dosage

31–50

400 mg every 12 h

15–30

300 mg every 12 h

<15 or receiving hemodialysis

200 mg every 12 h; on hemodialysis days, give dose after hemodialysis

Geriatric Patients

Dosage adjustment not required based on age; may be required based on age-related changes in renal function.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Teflaro

Contraindications

  • Known hypersensitivity to ceftaroline or other cephalosporins.1 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious, sometimes fatal, anaphylactic reactions and serious skin reactions reported in patients receiving β-lactam antibiotics.1 Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline.1

Discontinue drug if hypersensitivity occurs.1 Serious acute hypersensitivity (e.g., anaphylaxis) reactions require emergency treatment (e.g., epinephrine, airway management, oxygen, IV fluids, antihistamines, corticosteroids, vasopressors) as clinically indicated.1

Cross-hypersensitivity

Partial cross-sensitivity occurs among β-lactam antibiotics.1 27

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to ceftaroline, other cephalosporins, penicillins, or carbapenems.1 Contraindicated in patients hypersensitive to the drug or other cephalosporins; use with caution in those allergic to penicillin or other β-lactams.1

Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 12 13 14 15 16

C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all systemic anti-infectives, including ceftaroline, and may range in severity from mild diarrhea to fatal colitis.1 12 13 14 15 16 C. difficile produces toxins A and B which contribute to development of CDAD;1 13 12 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Consider CDAD if diarrhea develops during or after anti-infective therapy and manage accordingly.1 12 13 14 15 16 Obtain a careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 12 14 15 16 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 12 13 14 15 16

Hematologic Effects

Seroconversion from negative to positive direct antiglobulin (Coombs’) tests reported in approximately 11% of patients receiving ceftaroline in phase 3 clinical trials; no evidence of hemolytic anemia in these patients.1

Consider drug-induced hemolytic anemia in patients who develop anemia during or after ceftaroline treatment; perform diagnostic studies, including direct antiglobulin test.1 If drug-induced hemolytic anemia is suspected, consider discontinuing ceftaroline and administer supportive treatment (e.g., transfusion) as clinically indicated.1

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftaroline and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into milk.1 Use caution.1

Pediatric Use

Safety and efficacy not established in patients <18 years of age.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Substantially eliminated by kidneys; consider age-related decreases in renal function, select dosage with caution, and consider monitoring renal function.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not established; systemic clearance not expected to be altered by hepatic impairment.1

Renal Impairment

Dosage adjustments necessary in adults with Clcr ≤50 mL/minute, including those undergoing hemodialysis.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea,1 25 nausea,1 25 vomiting,1 constipation1 ), headache,25 rash,1 25 pruritus,25 hypokalemia,1 increased transaminases,1 25 phlebitis.1

Interactions for Teflaro

Does not inhibit CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4 in vitro; does not induce CYP1A2, 2B6, 2C8, 2C9, 2C19, or 3A4/5.1 Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.1

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Aminoglycosides

Amikacin: In vitro evidence of synergistic antibacterial effects against E. coli and K. pneumoniae that produce extended-spectrum β-lactamases (ESBL-producing), AmpC-derepressed Enterobacter cloacae, and Pseudomonas aeruginosa;22 no evidence of antagonism1 22

Aztreonam

In vitro evidence of indifferent antibacterial effects against ESBL-producing E. coli and K. pneumoniae, AmpC-derepressed E. cloacae, and Ps. aeruginosa;22 no evidence of synergism22 or antagonism1 22

Carbapenems

Meropenem: In vitro evidence of synergistic antibacterial effects against ESBL-producing E. coli and indifferent antibacterial effects against ESBL-producing K. pneumoniae, AmpC-derepressed E. cloacae, and Ps. aeruginosa;22 no evidence of antagonism1 22

Other anti-infectives

No in vitro evidence of antagonism between ceftaroline and azithromycin, daptomycin, levofloxacin, linezolid, tigecycline, or vancomycin1

Teflaro Pharmacokinetics

Absorption

Ceftaroline is administered as ceftaroline fosamil, a prodrug that is inactive until converted in vivo to ceftaroline by a plasma phosphatase.1 4

Plasma Concentrations

In healthy adults, peak plasma concentrations and AUC increase approximately in proportion to dose following single IV doses of 50–1000 mg of ceftaroline fosamil.1

No appreciable accumulation reported when 600-mg doses are given by IV infusion over 1 hour every 12 hours for up to 14 days in adults with normal renal function.1

Special Populations

In healthy adolescents 12–17 years of age, peak plasma concentrations and AUC after a single 8-mg/kg IV dose (600 mg in those weighing >75 kg) are 10 and 23% lower, respectively, compared with healthy adults who received a single 600-mg IV dose.1

Distribution

Extent

Limited data available regarding tissue distribution; animal data indicate ceftaroline is distributed into kidneys, skin, and lungs.4 9

Not known whether distributed into milk.1

Plasma Protein Binding

Approximately 20%;1 decreases slightly with increasing concentrations >1–50 mcg/mL.1

Elimination

Metabolism

Ceftaroline fosamil is rapidly converted in vivo to ceftaroline by a plasma phosphatase, principally during IV infusion.1 4 In addition, the β-lactam ring of ceftaroline is hydrolyzed to an inactive, open-ring metabolite (ceftaroline M-1).1

Ceftaroline is not a substrate of CYP isoenzymes.1

Elimination Route

Ceftaroline and its metabolites principally eliminated in urine by glomerular filtration.1 Following a single 600-mg IV dose of ceftaroline fosamil, approximately 88% is eliminated in urine (approximately 64% as unchanged drug, and 2% as ceftaroline M-1) and 6% is eliminated in feces within 48 hours.1

Removed by hemodialysis.1

Half-life

Adults: 2.7 hours.1

Special Populations

Pharmacokinetics in patients with hepatic impairment not established.1

AUC and half-life increased in patients with renal impairment.1 4

Stability

Storage

Parenteral

Powder for IV Infusion

2–8°C.1 May be stored at room temperature (≤25°C) for ≤7 days.1

Following reconstitution and dilution, may be stored in IV infusion bag for up to 6 hours at room temperature or up to 24 hours when refrigerated at 2–8°C.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1 HID

Compatible

Dextrose 2.5 or 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Drug CompatibilityHID
Y-Site Compatibility

Compatible

Acyclovir sodium

Amikacin sulfate

Aminophylline

Amiodarone HCl

Azithromycin

Bumetanide

Calcium chloride

Calcium gluconate

Ciprofloxacin

Cisatracurium besylate

Clindamycin phosphate

Co-trimoxazole

Cyclosporine

Dexamethasone sodium phosphate

Digoxin

Diltiazem HCl

Diphenhydramine HCl

Dopamine HCl

Doripenem

Enalaprilat

Esomeprazole sodium

Famotidine

Fentanyl citrate

Fluconazole

Furosemide

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Insulin, regular

Levofloxacin

Lidocaine HCl

Lorazepam

Mannitol

Meperidine HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Metoprolol tartrate

Metronidazole

Midazolam HCl

Milrinone lactate

Morphine sulfate

Moxifloxacin HCl

Multivitamins

Norepinephrine bitartrate

Ondansetron HCl

Pantoprazole sodium

Potassium chloride

Promethazine HCl

Propofol

Ranitidine HCl

Remifentanil HCl

Sodium bicarbonate

Tobramycin sulfate

Vasopressin

Voriconazole

Incompatible

Amphotericin B

Caspofungin acetate

Diazepam

Filgrastim

Labetalol HCl

Potassium phosphates

Sodium phosphates

Variable

Dobutamine HCl

Magnesium sulfate

Actions and Spectrum

  • Based on spectrum of activity, classified as a fifth generation cephalosporin.5 6 7 8 27

  • Like third and fourth generation cephalosporins, ceftaroline has an expanded spectrum of activity that includes both gram-positive and gram-negative bacteria.4 5 6 7 17 21 27 Unlike first, second, third, and fourth generation cephalosporins, ceftaroline has activity against methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant Staphylococcus aureus, ORSA).4 5 6 7 17 27

  • Usually bactericidal.1 4 17 22

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1

  • Spectrum of activity includes many gram-positive and gram-negative aerobic bacteria1 4 17 18 19 20 21 24 27 and some anaerobic bacteria.23

  • Gram-positive aerobes: Active in vitro against S. aureus (including MRSA, vancomycin-resistant S. aureus [VRSA], and daptomycin-nonsusceptible S. aureus),1 4 17 21 24 27 coagulase-negative staphylococci (including methicillin-resistant [oxacillin-resistant] strains),4 21 27 Streptococcus pneumoniae (including penicillin- or cefotaxime-resistant S. pneumoniae or multidrug-resistant S. pneumoniae [MDRSP]),1 4 18 19 20 21 24 27 S. pyogenes (group A β-hemolytic streptococci),1 4 21 27 S. agalactiae (group B streptococci),1 4 21 27 viridans streptococci,4 21 27 and S. dysgalactiae.1 Has only limited activity against Enterococcus faecalis; E. faecium are resistant.4 21

  • Gram-negative aerobes: Active in vitro against Escherichia coli,1 21 27 Klebsiella pneumoniae,1 21 27 K. oxytoca,1 and Haemophilus influenzae (including β-lactamase-producing strains).1 4 21 27 Also active in vitro against Citrobacter koseri,1 C. freundii,1 21 27 Enterobacter cloacae,1 21 27 E. aerogenes,1 27 Moraxella catarrhalis (including β-lactamase-producing strains),1 4 21 27 Morganella morganii,1 21 Pasteurella multocida,21 Proteus mirabilis,1 21 27 and H. parainfluenzae.1 Inactive against Pseudomonas aeruginosa4 27 .

  • Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) from the TEM, SHV or CTX-M families, AmpC cephalosporinases, class B metallo-β-lactamases, or serine carbapenemases are resistant.1 4 21 27

  • Although cross-resistance may occur between ceftaroline and other cephalosporins, some bacteria resistant to other cephalosporins may be susceptible to ceftaroline.1

Advice to Patients

  • Advise patients that antibacterials (including ceftaroline) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftaroline or other antibacterials in the future.1

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually resolves when the drug is discontinued.1 Importance of contacting a clinician if watery or bloody diarrhea occurs.1

  • Importance of informing clinicians of prior hypersensitivity reactions to ceftaroline, other cephalosporins, other β-lactam antibiotics, or other allergens.1 Importance of discontinuing the drug and immediately informing clinician if an allergic or hypersensitivity reaction occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ceftaroline Fosamil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion

400 mg

Teflaro

Forest

600 mg

Teflaro

Forest

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Forest Pharmaceuticals, Inc. Teflaro (ceftaroline fosamil) for injection prescribing information. St. Louis, MO; 2012 Oct..

2. Corey GR, Wilcox M, Talbot GH et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis. 2010; 51:641-50. [PubMed 20695801]

3. File TM, Low DE, Eckburg PB et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010; 51:1395-405. [PubMed 21067350]

4. Zhanel GG, Sniezek G, Schweizer F et al. Ceftaroline: a novel broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Drugs. 2009; 69:809-31. [PubMed 19441869]

5. Kollef MH. New antimicrobial agents for methicillin-resistant Staphylococcus aureus. Crit Care Resusc. 2009; 11:282-6. [PubMed 20001879]

6. Skrupky LP, Micek ST, Kollef MH. Bench-to-bedside review: Understanding the impact of resistance and virulence factors on methicillin-resistant Staphylococcus aureus infections in the intensive care unit. Crit Care. 2009; 13:222. [PubMed 19889197]

7. Ritchie DJ, Alexander BT, Finnegan PM. New antimicrobial agents for use in the intensive care unit. Infect Dis Clin North Am. 2009; 23:665-81. [PubMed 19665089]

8. Schirmer PL, Deresinski SC. Ceftobiprole: a new cephalosporin for the treatment of skin and skin structure infections. Expert Rev Anti Infect Ther. 2009; 7:777-91. [PubMed 19735220]

9. US Food and Drug Administration, Center for Drug Evaluation and Research. Pharmacology review(s) NDA application number 200327. From FDA website.

12. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55. [PubMed 20307191]

13. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

14. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

15. Bauer MP, Kuijper EJ, van Dissel JT et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009; 15:1067-79. [PubMed 19929973]

16. Jaber MR, Olafsson S, Fung WL et al. Clinical review of the management of fulminant Clostridium difficile infection. Am J Gastroenterol. 2008; 103:3195-203; quiz 3204. [PubMed 18853982]

17. Saravolatz L, Pawlak J, Johnson L. In vitro activity of ceftaroline against community-associated methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, and daptomycin-nonsusceptible Staphylococcus aureus isolates. Antimicrob Agents Chemother. 2010; 54:3027-30. [PubMed 20404122]

18. Jacobs MR, Good CE, Windau AR et al. Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother. 2010; 54:2716-9. [PubMed 20308374]

19. McGee L, Biek D, Ge Y et al. In vitro evaluation of the antimicrobial activity of ceftaroline against cephalosporin-resistant isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2009; 53:552-6. [PubMed 19015339]

20. Fenoll A, Aguilar L, Robledo O et al. In vitro activity of ceftaroline against Streptococcus pneumoniae isolates exhibiting resistance to penicillin, amoxicillin, and cefotaxime. Antimicrob Agents Chemother. 2008; 52:4209-10. [PubMed 18725443]

21. Ge Y, Biek D, Talbot GH et al. In vitro profiling of ceftaroline against a collection of recent bacterial clinical isolates from across the United States. Antimicrob Agents Chemother. 2008; 52:3398-407. [PubMed 18625769]

22. Vidaillac C, Leonard SN, Sader HS et al. In vitro activity of ceftaroline alone and in combination against clinical isolates of resistant gram-negative pathogens, including beta-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009; 53:2360-6. [PubMed 19349512]

23. Citron DM, Tyrrell KL, Merriam CV et al. In vitro activity of ceftaroline against 623 diverse strains of anaerobic bacteria. Antimicrob Agents Chemother. 2010; 54:1627-32. [PubMed 20100877]

24. Kosowska-Shick K, McGhee PL, Appelbaum PC. Affinity of ceftaroline and other beta-lactams for penicillin-binding proteins from Staphylococcus aureus and Streptococcus pneumoniae. Antimicrob Agents Chemother. 2010; 54:1670-7. [PubMed 20194704]

25. Corrado ML. Integrated safety summary of CANVAS 1 and 2 trials: Phase III, randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother. 2010; 65 Suppl 4:iv67-iv71. [PubMed 21115456]

26. Moisan H, Pruneau M, Malouin F. Binding of ceftaroline to penicillin-binding proteins of Staphylococcus aureus and Streptococcus pneumoniae. J Antimicrob Chemother. 2010; 65:713-6. [PubMed 20097788]

27. Andes DR, Craig WA. Cephalosporins. In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s principles and practices of infectious disease. 7th ed. New York: Churchill Livingstone; 2010:323-36.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013. Electronic update.

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