What determines the choice between oral (PO) and intravenous (IV) administration of medications?

Choice Between Oral (PO) and Intravenous (IV) Medication Administration

The oral route should be advocated as the first choice for medication administration whenever the patient has a functioning gastrointestinal tract, adequate oral intake, and is clinically stable. 1

Primary Decision Framework

When to Use Oral (PO) Administration

Clinical stability is the key determinant for oral therapy. Patients should meet four specific criteria before switching from IV to oral: improvement in cough and dyspnea, afebrile (≤100°F) on two occasions 8 hours apart, white blood cell count decreasing, and functioning gastrointestinal tract with adequate oral intake. 1 However, if the overall clinical response is favorable, it may not be necessary to wait until the patient is completely afebrile before making the switch. 1

• For chronic pain management, analgesics should be prescribed orally as the first-line route, with regular dosing rather than "as required" schedules. 1
• For community-acquired pneumonia, up to half of all hospitalized patients are eligible for oral switch therapy by hospital Day 3, and early switch can reduce hospital length of stay and may even improve outcomes compared with prolonged IV therapy. 1
• For uncomplicated streptococcal bloodstream infections, IV-to-PO step-down therapy after an average of 4.4 days of IV antibiotics was not associated with worse clinical outcomes and resulted in significantly shorter hospital stays (6.3 vs 12.6 days). 2

When to Use Intravenous (IV) Administration

IV administration is preferred when rapid achievement of therapeutic drug levels is critical, when the patient cannot absorb oral medications reliably, or when precise dosing is essential. 3

• In emergency and resuscitation scenarios, IV/IO bolus administration is the standard of care for medications like epinephrine, amiodarone, and adenosine, with the American Heart Association explicitly recommending "rapid IV/IO bolus with flush" for resuscitation medications. 4
• For critically ill patients, IV administration ensures reliable blood concentrations when gastrointestinal integrity is compromised. 5
• For severe infections requiring precise dosing, IV administration is preferred, as recommended for necrotizing infections where ertapenem 1g daily IV is the appropriate treatment option. 3
• For acute severe pain, IV administration allows for rapid pain relief and drug titration, making it superior to intramuscular administration which does not allow titration and causes additional pain. 4

Sequential vs Step-Down Therapy Considerations

The choice between maintaining equivalent drug levels (sequential therapy) or accepting lower levels (step-down therapy) depends on the specific medication. 1

• Sequential therapy (comparable serum levels IV or PO) is possible with doxycycline, linezolid, and most quinolones. 1
• Step-down therapy (decreased serum levels with oral administration) occurs with β-lactams and macrolides, but good clinical success has been documented with this approach. 1
• For opioids, the average relative potency ratio of oral to intravenous morphine is between 1:2 and 1:3, requiring dose adjustment when switching routes. 1

Alternative Routes When IV/PO Are Not Available

Intraosseous (IO) Administration

If IV access cannot be promptly obtained in an emergency, intraosseous administration is an acceptable alternative. 1 It is reasonable for providers to establish IO access if IV access is not readily available, and commercially available kits can facilitate IO access in adults. 1

• In pediatric emergencies, IO administration is preferred over endotracheal when IV access has not been achieved. 1
• Drug delivery via IO provides results almost the same as IV injection, though this route is currently underrepresented in clinical practice. 6

Endotracheal Administration

Endotracheal drug delivery should only be used as a last resort when no IV or IO access is available. 1 Although certain drugs (lidocaine, epinephrine, atropine, naloxone—memory aid: LEAN) can be administered endotracheally, this route results in lower blood concentrations than intravascular administration. 1

• Peak drug concentrations are lower with endotracheal administration compared to other routes. 6
• Recent animal studies suggest that lower epinephrine concentrations from endotracheal delivery may produce transient β-adrenergic effects, resulting in vasodilation and potentially detrimental effects including hypotension and lower coronary perfusion pressure. 1

Subcutaneous Administration

For certain medications like opioids and immunoglobulins, subcutaneous administration is a viable alternative with specific advantages. 1, 7

• For opioids, there is no difference between subcutaneous and IV administration in efficacy, safety, or side effects, with the average relative potency ratio of oral to subcutaneous morphine between 1:2 and 1:3. 1
• For immunoglobulins and biological therapies, 82% of patients preferred subcutaneous over IV administration, primarily due to greater convenience and ability to administer at home. 7

Critical Safety Considerations

Administration Rate and Technique

Even when using IV administration, the rate of infusion matters significantly for both safety and efficacy. 1

• Most drugs should be administered over several minutes to avoid transient excessive blood concentrations. 1
• Exceptions requiring rapid administration: Adenosine must be given as rapidly as possible followed by immediate rapid saline flush for efficacy. 1
• Exceptions requiring slow administration: Phenytoin/fosphenytoin requires slow infusion to minimize adverse events; amiodarone should be given over 20-60 minutes when a perfusing rhythm is present; procainamide requires 20 mg/min in adults; magnesium sulfate should be given over 10-20 minutes. 4

Peripheral IV Considerations

When using peripheral IV access during resuscitation, specific techniques enhance drug delivery to central circulation. 4

• Administer medications as bolus injection followed by a 20-mL saline flush. 4
• Briefly elevating the extremity during and after drug administration may help facilitate delivery to central circulation. 4
• Failure to follow with adequate saline flush can result in inadequate drug delivery. 4

Common Pitfalls to Avoid

• Never assume oral absorption is adequate in critically ill patients with compromised gastrointestinal function, shock states, or multi-organ failure. 5
• Do not delay IV access attempts excessively—limit time attempting peripheral IV access and establish intraosseous access if IV cannot be rapidly obtained in emergencies. 4
• Avoid intramuscular administration when IV/IO access is available, as IM does not allow for titration and causes unnecessary pain. 4
• Never mix multiple medications before administration through any IV route due to drug-drug interaction risks, and always flush the IV line with at least 30 mL of water before, between, and after each medication. 4
• Do not change antibiotic therapy within the first 72 hours unless there is marked clinical deterioration or bacteriologic data necessitate a change. 1