Clinical UM Guideline

 

Subject: Intravenous versus Oral Drug Administration in the Outpatient and Home Setting
Guideline #:  CG-DRUG-25 Publish Date:    06/06/2018
Status: Revised Last Review Date:    05/03/2018

Description

This document addresses the use of intravenous (IV) versus oral (PO) versions of exactly the same drug. The use of different drugs within the same therapeutic class is not addressed in this document.

Certain IV drugs have documented clinical efficacy that is bio-equivalent to the PO route of administration. When this is the case, and a stable individual requires long-term drug therapy, then PO administration of the drug is generally preferred. The purpose of this document is to help ensure that the most effective and least invasive form of drug administration is used when the IV and PO routes are bio-equivalent and used in the outpatient or home setting.

Clinical Indications

Medically Necessary:

The use of the oral route of drug administration is considered medically necessary if both of the following are met:

The use of the intravenous route of administration is considered medically necessary if both of the following are met:

*Examples of bio-equivalent intravenous and oral medications are listed in Table 1 Examples of Bio-Equivalent Intravenous and Oral Medications in the Discussion section.

Not Medically Necessary:

The intravenous route of administration for medications that have oral preparations which are bio-equivalent and the individual can tolerate oral intake is considered not medically necessary.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

 

Examples include, but are not limited to, the following injectable drugs:

C9113

Injection, pantoprazole sodium, per vial

C9462

Injection, delafloxacin, 1 mg

J0744

Injection, ciprofloxacin for intravenous infusion, 200 mg

J1450

Injection, fluconazole, 200 mg

J1956

Injection, levofloxacin, 250 mg

J2020

Injection, linezolid, 200 mg

J2280

Injection, moxifloxacin, 100 mg

S0030

Injection, metronidazole, 500 mg

S0039

Injection, sulfamethoxazole and trimethoprim, 10 ml

S0164

Injection, pantoprazole sodium, 40 mg

 

 

ICD-10 Diagnosis

 

 

All diagnoses

Discussion/General Information

The United States (US) Food and Drug Administration (FDA) defines bio-equivalence as:

The absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

If the PO and IV routes of select medications are bio-equivalent (per the FDA approved package insert), there would be no apparent clinical benefit to using the IV over the PO route unless the gastrointestinal tract is somehow compromised.

A Cochrane review (Kilburn, 2010) reported on the safety and efficacy of interventions for cellulitis. It was determined that no two trials reported on the same drug. Many trials compared the addition of corticosteroid to antibiotic treatment versus antibiotic treatment alone. The authors concluded “There is a need for trials to evaluate the efficacy of oral antibiotics against intravenous antibiotics in the community setting as there are service implications for cost and comfort.”

Table 1 Examples of Bio-Equivalent Intravenous and Oral Medications

Flouroquinolone Antibiotics

Ciprofloxacin
Delafloxacin
Levofloxacin
Moxifloxacin

Other Antibiotics

Clarithromycin
Linezolid
Sulfamethoxazole/Trimethoprim
Fluconazole
Metronidazole

Proton Pump Inhibitors

Lansoprazole
Pantoprazole

   
References

Peer Reviewed Publications:

  1. Aneziokoro CO, Cannon JP, Pachucki CT, Lentino JR. The effectiveness and safety of oral linezolid for the primary and secondary treatment of osteomyelitis. J Chemother. 2005; 17(6):643-650.
  2. Angeli P, Guarda S, Fasolato S, et al. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Aliment Pharmacol Ther. 2006; 23(1):75-84.
  3. Ballow C, Lettieri J, Agarwal V, et al. Absolute bioavailability of moxifloxacin. Clin Ther. 1999; 21(3):513-522.
  4. Barquist ES, Gomez-Fein E, Block EF, et al. Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: a randomized crossover clinical trial. J Trauma. 2007; 63(1):159-163.
  5. Breilh D, Jougon J, Djabarouti S, et al. Diffusion of oral and intravenous 400 mg once-daily moxifloxacin into lung tissue at pharmacokinetic steady-state. J Chemother. 2003; 15(6):558-562.
  6. Broder KW, Moise PA, Schultz RO, et al. Clinical experience with linezolid in conjunction with wound coverage techniques for skin and soft-tissue infections and postoperative osteomyelitis. Ann Plast Surg. 2004; 52(4):385-390.
  7. Chien SC, Rogge MC, Gisclon LG, et al. Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses. Antimicrob Agents Chemother. 1997; 41(10):2256-2260.
  8. Chu SY, Deaton R, Cavanaugh J. Absolute bioavailability of clarithromycin after oral administration in humans. Antimicrob Agents Chemother. 1992; 36(5):1147-1150.
  9. Fischer MA, Solomon DH, Teich JM, Avorn J. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients. Arch Intern Med. 2003; 163(21):2585-2589.
  10. Gerloff J, Mignot A, Barth H, Heintze K. Pharmacokinetics and absolute bioavailability of lansoprazole. Eur J Clin Pharmacol. 1996; 50(4):293-297.
  11. Giordano P, Song J, Pertel P, et al. Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection. Int J Antimicrob Agents. 2005; 26(5):357-365.
  12. Greenberg RN, Newman MT, Shariaty S, Pectol RW. Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis. Antimicrob Agents Chemother. 2000; 44(1):164-166.
  13. Huber R, Hartmann M, Bliesath H, et al. Pharmacokinetics of pantoprazole in man. Int J Clin Pharmacol Ther. 1996; 34(5):185-194.
  14. Itani KM, Weigelt J, Li JZ, Duttagupta S. Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). In J Antimicrob Agents. 2005; 26(6):442-448.
  15. Klepser ME, Zhu Z, Nicolau DP, et al. Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS. Pharmacotherapy. 1996; 16(4):656-662.
  16. Liu S, Liu X, Chen S, et al. Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials. PLoS One. 2017; 12(11):e0188644.
  17. Mahar PJ, Rana JA, Kennedy CS, Christopher NC. A randomized clinical trial of oral transucosal fentanyl citrate versus intravenous morphine sulfate for initial control of pain in children with extremity injuries. Pediatr Emerg Care. 2007; 23(8):544-548.
  18. Politi JR, Davis RL 2nd, Matrka AK. Randomized Prospective Trial Comparing the Use of Intravenous versus Oral Acetaminophen in Total Joint Arthroplasty. J Arthroplasty. 2017; 32(4):1125-1127.
  19. Pratha V, Hogan DL, Lynn RB, et al. Intravenous pantoprazole as initial treatment in patients with gastroesophageal reflux disease and a history of erosive esophagitis: a randomized clinical trial. Dig Dis Sci. 2006; 51(9):1595-1601.
  20. Pue MA, Laroche J, Meineke I, de Mey C. Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects. Eur J Clin Pharmacol. 1993; 44(6):575-578.
  21. Rao N, Ziran BH, Hall RA, Santa ER. Successful treatment of chronic bone and joint infections with oral linezolid. Clin Orthop Relat Res. 2004; (427):67-71.
  22. Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet. 2003; 42(13):1129-1140.
  23. Stass H, Kubitza D. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother. 1999; 43(Suppl B):83-90.
  24. Stockmann C, Ampofo K, Pavia AT, et al. Comparative effectiveness of oral versus outpatient parenteral antibiotic therapy for empyema. Hosp Pediatr. 2015; 5(12):605-612.
  25. Welshman IR, Sisson TA, Jungbluth GL, et al. Linezolid absolute bioavailability and the effect of food on oral bioavailability. Biopharm Drug Dispos. 2001; 22(3):91-97.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2012; (12): CD006921.
  2. Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014; (7): CD005088.
  3. Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010; (6):CD004299.
  4. Pohl A. Modes of administration of antibiotics for symptomatic severe urinary tract infections. Cochrane Database Syst Rev. 2007; (4):CD003237.
  5. Rojas MX, Granados C. Oral antibiotics versus parenteral antibiotics for severe pneumonia in children. Cochrane Database Syst Rev. 2006; (2):CD004979.
  6. U.S. FDA Center for Drug Evaluation and Research (CDER). Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations. Rockville, MD: FDA. March 2003. Available at: https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/
    abbreviatednewdrugapplicationandagenerics/ucm154838.pdf
    .  Accessed on May 23, 2018.
  7. Vidal L, Ben-Dor I, Paul M, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2013; (10):CD003992.
Index

Ciprofloxacin
Clarithromycin
Delafloxacin
Fluconazole
Intravenous Drug Administration
Lansoprazole
Levofloxacin
Linezolid
Metronidazole
Moxifloxacin
Oral Drug Administration
Pantoprazole
Sulfamethoxazole/Thrimethoprim

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Added delafloxacin to the list of examples of bioequivalent flouroquinolone antibiotics. Examples of bio-equivalent intravenous and oral medications removed from the clinical indications section and moved to the discussion section. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Discussion and References sections. Updated coding section to add C9462.

Reviewed

05/04/2017

MPTAC review. Updated references.

Revised

05/05/2016

MPTAC review. Minor grammar change to position statement, changed IV to intravenous. Updated Discussion and References sections. Removed ICD-9 codes from Coding section.

Reviewed

05/07/2015

MPTAC review. Updated Description and References sections.

Reviewed

05/15/2014

MPTAC review. Updated References.

Reviewed

05/09/2013

MPTAC review.

Reviewed

05/10/2012

MPTAC review. Updated Discussion/General Information.

Reviewed

05/19/2011

MPTAC review. Title change to “Intravenous versus Oral Drug Administration in the Outpatient and Home Setting.” Updated Discussion/General Information and References.

Reviewed

05/13/2010

MPTAC review.

Reviewed

05/21/2009

MPTAC review. Updated References. Removed Place of Service section.

New

05/15/2008

MPTAC review. Initial document development.