2. Learning objectives
Explain the rationale behind an intravenous (IV) to oral (PO) therapy
conversion
Benefits of IV to PO therapy conversion
Types of IV to PO therapy conversion
Identify common medications that are included in an IV to PO therapy
conversion program
Identify patients who are candidates to convert from IV to PO therapy
Describe the exclusion criteria that prohibit a conversion from IV to PO
therapy
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3. INTRODUCTION
There are generally two methods used to design dosage regimen
1. Empirical (pharmacodynamic) based dosage regimens design
Involves administration of a drug in a certain quantity, then noting the
therapeutic response, after which the dosage and the dosing interval modified.
Based on empirical clinical data, personal experience and clinical observations.
Example: Warfarin (International normalized ratio), Insulin (Sliding scale)
2. Pharmacokinetic based dosage regimen design
Assumes the therapeutic & toxic effects are proportional to the plasma conc. of
drug at the receptor sites or amount of drug in the body
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4. INTRODUCTION
Rational dosing of antimicrobial agents
From the viewpoint of pharmacodynamics,
antimicrobial agents may be divided into three major
groups.
Group I: ß-lactams
Group II: Vancomycin, carbapenems, macrolides, and clindamycin
Group III: Aminoglycosides, fluoroquinolones, and metronidazole
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5. Group I: ß-lactams
These agents have a kill rate that is concentration-independent as long
as the concentration is above the minimum inhibitory concentration
(MIC).
Also, these agents have no significant post-antibiotic effect (PAE).
PAE is the persistent suppression of bacterial growth following antibiotic
exposure.
Strategy for best results: maximize exposure time during which the
plasma concentration exceeds MIC.
This may be achieved by giving smaller doses more frequently;
ultimately, continuous IV infusion of ß-lactams would achieve the best
results.
In fact, when penicillin was first introduced, it was administered by
continuous infusion; only later was it given intermittently, largely for
the sake of convenience.
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6. Group II: Vancomycin, carbapenems,
macrolides, and clindamycin
These agents have a kill rate that is concentration-independent as
long as the concentration is above the MIC.
Also, these agents also have an intermediate post-antibiotic effect,
therefore serum levels may be allowed to drop below the MIC for a
short period.
Strategy for best results: maximize exposure time during which the
plasma concentration exceeds MIC.
This may be achieved by giving smaller doses more
frequently (i.e., 500 mg 6 hrs is better than 1000 mg q 12 hrs).
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7. Group III: Aminoglycosides, fluoroquinolones,
and metronidazole
These agents have concentration-dependent kill rate and
a significant post-antibiotic effect.
The PAE exhibited by this group will prevent bacterial re-growth when
tissue levels fall below the MIC for an extended period of time.
Strategy for best results: Aim for a "good peak" to maximize the ratio
of Peak to MIC.
This is achieved by giving larger doses less frequently.
In the case of aminoglycosides, "give the kidney a break" too by allowing
for a short (2 - 4 hrs) drug-free period to minimize nephrotoxicity.
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8. CLASSIFICATIONS OF THERAPY
To help physicians in the selection of optimal antimicrobial
therapy pharmacists need to know regarding antimicrobial use
Clinical situations in which antimicrobial agents are regularly
used are defined as follows
Prophylactic Use
Therapeutic Use:
Empiric Therapy
Known Pathogen Therapy
Switch Therapy/Conversion from IV to PO
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9. IV to PO Therapy Conversion
IV-to-oral antibiotic switching programs have been adopted in many
countries way back in the 1990s.
Ever since then, many studies have been carried out and had convincingly
demonstrated the efficacy, safety and its economic impact in the clinical
institutions.
In the clinical situation of “conversion therapy use", oral antimicrobials
replace intravenous usage for completion of therapy.
Intravenous therapy is almost always employed in serious infections to
ensure maximal serum levels.
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10. IV to PO Therapy Conversion
The ideal route of administration for any medication is one that achieves
serum concentrations sufficient to produce the desired effect.
Converting IV to PO therapy to continue treatment after an already
adequate course of IV therapy is now common practice.
The available oral formulations on the market are
easier to administer,
safe, and
achieve desired therapeutic concentrations, thus making the PO route
an ideal choice.
Patients are more comfortable if they do not have an IV catheter in place.
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11. Types of IV to PO Therapy Conversions
1. Sequential Therapy
2. Switch Therapy
3. Step-Down Therapy
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12. Sequential therapy
It refers to the act of replacing a parenteral version of a medication with its
oral counterpart.
An example is the conversion of famotidine 20 mg IV to famotidine 20 mg
PO, Metronidazole 500 mg q8h IV to Metronidazole 500 mg q8h PO;
Ciprofloxacin 400 mg q12h to Ciprofloxacin 500 or 750mg q12h .
There are many classes of medications that have oral dosage forms that
are therapeutically equivalent to the parenteral form of the same
medication.
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13. Switch therapy
It is used to describe a conversion from an IV medication to
the PO equivalent that may be within the same class and
have the level of potency, but is a different compound.
An example is the conversion of IV pantoprazole to rapidly
dissolving lansoprazole tablets or omeprazole capsules.
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14. Step-down therapy
It refers to converting from an injectable medication to an
oral agent in another class or to a different medication
within the same class where the frequency, dose, and the
spectrum of activity (in the case of antibiotics) may not be
exactly the same.
Converting from ampicillin/sulbactam 3g IV q6h to
amoxicillin/clavulanate 875 mg PO q12 h.
Converting from IV Ceftriaxone to oral Cefpodoxime, may be also an
option in some cases.
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15. Benefits of IV-to-PO Therapy Conversion
Pharmacoeconomic and Clinical benefits
Perhaps the most obvious positive of converting from IV to PO is that drug
costs are decreased, as most PO medications are less expensive than their
IV counterparts.
In many cases, PO drugs are more easily acquired and handled, and are
more convenient for the pharmacy because they take up less space and are
easier to store in larger quantities than IV medications.
Beyond saving on the actual cost of the medication, additional savings are
realized by eliminating IV sets and reducing nursing and pharmacy
personnel time spent on IV-related activities.
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16. Benefits of IV to PO therapy conversion
Who is benefited?
Patient, health care providers and Health setting
Removal of IV lines reduces the risk factors for hospital acquired
bacteremia, endocarditis and phlebitis (secondary infections)
Decrease patient discomfort and enables independence and mobility
Possibility of early discharge and reducing length of hospital stay
Reduce treatment costs (oral being less expensive than IV and
decreasing length of hospital stay)
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17. Benefits of IV to PO therapy conversion
Saves nursing/medical/pharmacy time and hence decrease work
load/hours required and cost, e.g. No. of hours required for
administering IV antibiotics reduced by 350 hrs/annually
Releasing inpatient resources for reallocation
Incase of antibiotic resistant pathogens potential transmission with in
health care setting reduced
Patient more likely to receive antibiotic at correct time
Potential reduction in adverse effects and errors in preparation
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18. Classes of Medications
The ideal medication to include in an IV to PO therapy
conversion program has several characteristics.
Excellent bioavailability (ideally greater than 80%),
Well tolerated upon administration,
Its use should be supported by clinical data,
Availability of multiple oral dosage forms (e.g., tablets and liquids),
Dosing at a frequency equivalent to or less than the IV formulation.
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19. Classes of Medications
Medications involved in conversion therapy include antibiotics,
analgesics, antipsychotics, antivirals, cardiology and neurologic
medications.
In most hospitals, the primary drugs included in the IV-to-PO therapy
conversion programs are antibiotics.
In each class of medications it is generally considered to know the general
pharmacokinetic and pharmacodynamic issues as choice of oral agents is
guided by pk and pd principles.
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20. Oral Biovailability of some medicines formulations
available as IV and PO formulations
Oral Bioavailability
<50% 50-80% 80-100%
Acyclovir
Ampicillin
Azithromycin (but well distributed into
tissues)
Cefuroxime axetil (increases with
food)
Cefixime
Cefpodoxime
Diltiazem
Famotidine
Cefixime
Cefpodoxime
Cimetidine
Ciprofloxacin
Dexamethasone
Digoxin
Gemifloxacin
Itraconazole
Levothyroxine
Metoprolol
Amoxicillin, Ceftibuten
Cefadroxil, Cefaclor
Cefoprozin, Cephalexin
Chloramphenicol
Clindamycin, Doxycycline
Esomeprazole, Fluconazole
Gatifloxacin, Hydrocortisone
Lansoprazole, Levofloxacin
Linezolid, Methylprednisolone
Metronidazole
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21. Common IV-to-PO conversions of some
medications based on their bioavailability
Common IV To PO Conversions
Medication Bioavailability IV-PO Comments
Acyclovir 10 - 30% with dose NA Acyclovir 400 mg q8h = Acyclovir 800
mg 5xper day
Azithromycin 34 - 52% 1:1 IV and PO dosing 250-500mg QD
Bactrim 90 - 100% 1:1 5mL (1 vial) = 1 SS Tab; 2 vials = DS
tab
Clindamycin 90% 1:1 Clindamycin 300 to 450 q6h
Cyclosporine 10 - 89% (mean 30%) Variable IV Dose essentially 33% of PO dose
Digoxin 60 - 80% NA IV dose by 20-25% from PO
Famotidine 20 - 66% 1:1 20mg IV = 20mg PO
Fluconazole 90% 1:1 200mg IV = 200mg PO
Furosemide 60 - 70% 1:2 40mg IV = 80mg PO (variable)
Ganciclovir 5% NA PO Maintenance 1000mg TID
IV Treatment 5mg/kg q12
IV Maintenance 5mg/kg QD
Haloperidol 60% 1:2 24mg PO = 15mg IV
Labetolol 25 - 40% NA Once BP Controlled with IV therapy,
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22. Oral alternatives to IV antibiotics
PARENTERAL AGENT ORAL AGENT
Penicillin G (1-4 Mu Q4-6h) Pen VK 500 mg Qid
Nafcillin (1 g Q4h) Dicloxacillin 500 mg Qid
Ampicillin (2 g Q6h) Amoxicillin 500 mg Tid
Cefazolin (1 G Q8h) Cephalexin 500 mg Qid
Cefuroxime (1.5 g Q8h) Cefuroxime Axel 500mg Bid
Cefoxitin (1-2 g Q8h To 6h) Amox/Clavu 875 mg Bid
Clindamycin (300-600 mg Q8h) Clindamycin 300-450 mg Qid
Chloramphenicol Chloramphenicol
Linezolid Linezolid
Azole antifungals Azole antifungals
Doxycycline Doxycycline
Metronidazole (500 mg Q12h) Metronidzole 500 mg Tid
Ciprofloxacin (400 mg Q12h) Ciprofloxacin 750 mg Bid
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23. Indications to switch to oral therapy
Many patients are given intravenous antibiotics at the time of admission to
hospital.
As they improve and investigations reveal the site and extent of any
infective process, it may be appropriate:
to discontinue antibiotics OR
if the patient’s condition allows, to change from the IV to PO therapy
Consider switch to oral antibiotics after 48 hours.
If not initially appropriate, continue to review need for IV therapy every
24 hours
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24. Criteria for IV to PO therapy Conversion
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No clinical diagnosis that requires intravenous therapy for the full treatment
course (i.e., meningitis, bacteremia, osteomyelitis, septic arthritis, infective
endocarditis, device related infections, abscesses, empyema and peritonitis);
?????????? and Etiologically well defined disease
Completion of 48-72 hrs of IV therapy
Patient has adequate gastrointestinal absorption of drugs (i.e., no diarrhea,
no vomiting), that is function git, no LoC;
Afebrile for >24 hours;
Signs and symptoms related to infection are improving (improving clinical
status) and the white blood cell count is normalizing (no neutropenia).
25. Clinical improvement
All infections:
No evidence of hypotension or shock, clinician documented impression
of clinical improvement.
Pneumonia:
At baseline oxygen requirements, PO2 > 55 mmHg or O2 saturation
>90%; stable or improved pulmonary infiltrates; improvement in cough,
sputum production, hemoptysis if present.
Skin/soft tissue infection:
Cessation of purulent drainage from a wound if present, improved
edema/induration/erythema of cellulitic area and/or wound.
Urinary tract infection:
Improved dysuria, suprapubic pain, costovertebral angle tenderness,
decreased pyuria.
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26. Patients excluded from IV to PO therapy
conversion
NPO order on chart AND
Not tolerating at least clear fluid diet AND
All medications by non oral route OR
Critical care patient OR
Bacteremia OR
Neutropenia (ANC less than 1 x 109 /L) OR
Treatment of endocarditis, CNS infections, osteomyelitis, septic arthritis
Fluoroquinolone Exclusion for those receiving continuous enteral feeds
Fluconazole Exclusion for those with candidemia treated for < 7 days
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27. Patients excluded from IV to PO therapy
conversion
Antiepileptic Medications
Patients who are at risk for actively seizing or are unable to tolerate oral
medications without risk of aspiration are not appropriate candidates for
PO therapy.
Cardiovascular
Patients with unstable cardiac conditions or for whom frequent dose
changes are occurring (e.g., through IV drip titration) are not good
candidates for PO therapy.
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28. IV to PO therapy conversion guideline/protocol
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Does the patient fulfill any of the criteria to continue IV therapy?
Criteria for continuing IV therapy
Continuing signs of sepsis, i.e. 2 or more of the following
Temperature > 38oC or <36oC
Tachycardia-heart rate > 90von
Tachypnoea-respiratory rate > 20 breaths/minute
WBC >12 or <4
Febrile with neutropenia (neutrophils <1)
Serious deep seated infection that requires IV therapy e.g.
Meningitis
Infective endocarditis
Infection of a prosthetic device
Severe cellulitis or necrotizing fasciitis
Septic arthritis
Osteomyelitis
Note: Oral switch may be appropriate for some on these infections. Discuss
29. Appropriate Oral Antimicrobial
IV Oral Conversion
Amoxicillin 500 mg-1 g tid Amoxicillin 500 mg-1g tid
Benzylpencillin 1.2 g – 2.4 g qid Amoxicillin 500mg -1 g tid
Ciprofloxacin 400 mg Ciprofloxacin 500 mg bid or 750 mg bid
if pseudomonas spp. isolated
Clarithromycin 500 mg bid Clarithromycin 500 mg bid
Clindamycin 600 mg-1.2 g qid Clindamycin 300 mg-450 mg qid
Co-amoxiclav 1.2 g tid Co-amoxiclav 625 mg tid
Flucloxacin 1g -2 g qid Flucloxacin 500 mg-1 g qids
Gentamicin 7 mg/kg /qd Cirprofloxacin 500 mg bid or 750 mg
bid if pseudomonas spp. isolated
Levofloxacin 500 mg bid Levofloxacin 500 mg bid
Metronidazole 500 mg tid Metronidazole 500 mg tid
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33. Ideal Antibiotic
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Side effect profile
Nausea, diarrhea, vomiting or abdominal distress
Well tolerated by GI tract with minimal GI side effects
Minimal potential for non-C. difficile/C. difficile diarrea
Low allergic potential
Beta-lactams, sulfonamides
Low incidence of serious side effects
Seizure: Ciprofloxacin
Drug-drug interaction
Milk products
Other co-administered drugs
34. Myths of IV to PO Therapy Conversion
Infectious diseases need intravenous treatment and conversion to
oral therapy should be used sparingly and only at discharge.
Oral antimicrobials are not equivalent to intravenous therapy.
The oral antimicrobial must be the same medication or from the
same medication class as the intravenous agent.
IV is better than oral
All patients with infectious disease need IV treatment
Medicare will not reimburse for the care of inpatients on oral
therapy.
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