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.
The use of the oral route of drug administration is considered medically necessary if both of the following are met:
- There is clear, well-documented evidence that the intravenous and oral preparations of the drug are bio-equivalent*; and
- Individual can tolerate enteral intake, including via oral, nasogastric or percutaneous endoscopic gastrostomy tube routes.
The use of the intravenous route of administration is considered medically necessary if both of the following are met:
- The efficacy of the intravenous form is required; and
- The individual cannot tolerate enteral medication administration. Examples include, but are not limited to:
- Gastrointestinal malabsorption
- Bowel obstruction
*Examples of bio-equivalent intravenous and oral medications include, but are not limited to:
Proton Pump Inhibitors
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.
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.
| ||Examples include, but are not limited to, the following injectable drugs:|
|C9113||Injection, pantoprazole sodium, per vial|
|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|
| || |
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."
Peer Reviewed Publications:
- 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.
- 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.
- Ballow C, Lettieri J, Agarwal V, et al. Absolute bioavailability of moxifloxacin. Clin Ther. 1999; 21(3):513-522.
- 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.
- 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.
- 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.
- 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.
- Chu SY, Deaton R, Cavanaugh J. Absolute bioavailability of clarithromycin after oral administration in humans. Antimicrob Agents Chemother. 1992; 36(5):1147-1150.
- 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.
- Gerloff J, Mignot A, Barth H, Heintze K. Pharmacokinetics and absolute bioavailability of lansoprazole. Eur J Clin Pharmacol. 1996; 50(4):293-297.
- 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.
- 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.
- Huber R, Hartmann M, Bliesath H, et al. Pharmacokinetics of pantoprazole in man. Int J Clin Pharmacol Ther. 1996; 34(5):185-194.
- 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.
- Klepser ME, Zhu Z, Nicolau DP, et al. Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS. Pharmacotherapy. 1996; 16(4):656-662.
- 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.
- 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.
- 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.
- 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.
- Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet. 2003; 42(13):1129-1140.
- 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.
- 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.
- 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:
- 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.
- Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014; (7): CD005088.
- Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010; (6):CD004299.
- Pohl A. Modes of administration of antibiotics for symptomatic severe urinary tract infections. Cochrane Database Syst Rev. 2007; (4):CD003237.
- Rojas MX, Granados C. Oral antibiotics versus parenteral antibiotics for severe pneumonia in children. Cochrane Database Syst Rev. 2006; (2):CD004979.
- 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: http://www.fda.gov/ohrms/dockets/ac/03/briefing/3995B1_07_GFI-BioAvail-BioEquiv.pdf . Accessed on March 29, 2016.
- Vidal L, Ben-Dor I, Paul M, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. CochraneDatabase Syst Rev. 2013; (10):CD003992.
Intravenous Drug Administration
Oral Drug Administration
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.
|Revised||05/05/2016||Medical Policy & Technology Assessment Committee (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. No changes to Clinical Indications.|
|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. No change to Clinical Indications.|
|Reviewed||05/21/2009||MPTAC review. Updated References. Removed Place of Service section.|
|New||05/15/2008||MPTAC review. Initial document development.|