The Family Practice Newsletter
that causes blurred vision or
hypotension will also impair some
patients’ ability to drive.
December/January
2012-2013
Inside this Issue

DWM: Driving While
Medicated

Extended Indications
for Rivaroxaban
(Xarelto®) Use
DWM: Driving
While Medicated
Josh Ebbing, PharmD Candidate

APAP and Ibuprofen as
Antipyretics
Don’t Forget!
Comprehensive $4
List
Find it at:
www.doctorsfp.com
 pharmacy page
Newsletter Contact Information:
Megan Keller, PharmD
MKELLER4@OhioHealth.com
Doctors Hospital Family Practice
2030 Stringtown Road, Suite 300
Grove City, Ohio 43123
1
When patients are prescribed new
medications, they are often warned of
possible side effects, such as dry mouth,
insomnia or an occasional rash.
However, patients are rarely warned
about the dangers of driving while they
are on their medications or when
starting a new medication. This can
lead to an array of accidents because the
patient does not know what to expect.
A recent study shows that as many as 3
out of every 100 vehicle accidents can
be attributed to a driver that was
experiencing some side effect from a
prescription medication they were
taking1. The National Highway Traffic
Safety Administration (NHTSA) has
also release several statements over the
past few years warning drivers about the
potential danger of driving while using
medications as well as patient’s
diagnosed with conditions that may alter
perception when driving2. The NHTSA
also suggests that at least once year,
patients have a discussion with their
doctor and pharmacist to evaluate the
need for any changes in therapy. This is
especially important as patient’s age and
become more susceptible to side effects.
As health care professionals, we often
think only of medications that cause
drowsiness as ones to be wary of when
operating a vehicle. But any medication
Common classes associated with fatigue
and others effects that may impair
vehicle operation:
 Antihypertensives (ACE-I, BB,
CCB, diuretics, etc)
 Sedatives (barbiturates,
benzodiazepines)
 Analgesics (opioids)
 Skeletal muscle relaxants
 Antihistamines
 Anticholinergics (oxybutynin)
 Tricyclic Antidepressants
 Anti-diabetics (Glyburide>Hypoglycemia)
It all comes down to educating patients
and providing them with the proper
information or directing them to the
place where they can find it. A local
pharmacist will be able to give patients
a detailed description of the possible
effects that their medications may
cause. For patients that want
reassurance, you can direct them to the
RoadwiseRx.com website. This site
allows patients to enter all of their
medications and gives them an
abbreviated side effect panel to show
how their medications may affect their
ability to operate a vehicle.
Extended Indications
for Rivaroxaban
(Xarelto®) Use
Jennifer Focht, PharmD Candidate
Long-term anticoagulation therapy can
prove to be a challenge for both patients
and providers. For nearly 50 years,
warfarin (Coumadin®) has been the
mainstay for oral anticoagulation
therapy. However, warfarin has a
narrow therapeutic window that requires
. . . . . . . . . . . . . . . . . . . . . .
The Family Practice Newsletter – December/January 2012-13
RIVAROXABAN KEY POINTS
 Factor Xa inhibitor
 No monitoring required
 Standard dosing based on indication
 Indications now include treatment of
DVTs and PEs and risk reduction for
recurrent DVTs and PEs
 Previous indications were reduction
of stroke risk in a-fib patients and risk
reduction of DVTs and PEs in
patients after knee and hip
replacement
frequent monitoring due to its many
drug-drug, drug-food, and drug-disease
state interactions as well as the genetic
variations leading to varied patient
response. Because of this, warfarin
requires frequent monitoring and
sometimes lifestyle changes for the
patient.
Rivaroxaban (Xarelto®) is an oral
factor Xa inhibitor that does not require
routine monitoring. Indications for
rivaroxaban were expanded by the FDA
on November 2, 2012. Indications now
include the treatment of both deep vein
thrombosis (DVT) and pulmonary
embolism (PE) as well as reduction of
the risk for recurrent DVTs and PEs
following initial treatment. These new
indications were based on the results of
the EINSTEIN trials that showed safety
and efficacy of rivaroxaban. Previous
FDA-approved indications include
reduction of stroke risk in non-valvular
atrial fibrillation patients as well as risk
reduction of DVTs and PE in patients
after knee or hip replacement surgery.
The EINSTEIN-DVT and EINSTEINPE studies included both an acute phase
(3 weeks of 15mg bid followed by 20
mg daily for 3, 6, or 12 months) and a
continuation phase for patients
completing 6-12 months of the acute
phase (EINSTEIN-EXT). During the
acute phase patients were randomized to
either rivaroxaban or standard of care
enoxaparin and warfarin treatment and
non-inferiority was assessed for both
use in acute DVT and PE separately. In
the trial extension, rivaroxaban was
compared to placebo for superiority of
preventing recurrent DVTs or PEs.
2
The acute phase DVT and PE studies
both demonstrated non-inferiority to
standard of care in recurrence of venous
thromboembolism (2.1% vs 3.0%, P
<0.001; 2.1% vs 1.8% P=0.003,
respectively) and similar safety profiles
for both major and non-major bleeding.
In the continuation study, superiority
over placebo was found, however, given
the nature of the drug, the risk of bleeds
was increased over placebo. The trial
committee assessed the risk verses
benefit ratio by looking at the
percentage of patients who chose to
restart rivaroxaban after a bleeding
event (81%). This suggests that the
benefit of decreased recurring events
out-weighed the increased risk of bleeds
for the patients and clinicians involved.
Because of its non-inferiority to
warfarin and similar safety profiles, and
attractive benefit of no routine efficacy
monitoring required, rivaroxaban may
be considered as an alternative to
warfarin therapy.
medications for fever treatment. Both of
these drugs have shown safety and
effectiveness when used in
recommended doses.
When starting patients on rivaroxaban,
it will be important to remember to
avoid concomitant use with CYP3A4
inducers and inhibitors as this
combination may affect the safety and
efficacy of rivaroxaban. Patients should
also avoid large amounts of grapefruit
juice as it may increase levels of
rivaroxaban therapy. To change a
patient from warfarin to rivaroxaban,
the patient simply discontinues warfarin
therapy and initiates rivaroxaban
therapy as soon as the INR falls to <3.0.
Ibuprofen is a non-steroidal antiinflammatory drug (NSAID) that
decreases prostaglandin synthesis by
inhibiting cyclooxygenase-1 and 2
(COX-1 and 2) thereby producing
antipyretic, analgesic and antiinflammatory effects. The antipyretic
dose for those 6 months to 12 years old
is 5 mg/kg/dose (for temperature <
102.5°F) and 10 mg/kg/dose (for
temperature > 102.5°F), given every six
to eight hours. The maximum dose for
pediatrics is 40 mg/kg/day. For adults,
the typical antipyretic dose is 200-400
mg every four to six hours (maximum
dose 1200 mg/24 hours; unless under
physician supervision, where daily
doses ≤ 2400 mg may be used). Studies
have shown that ibuprofen has superior
effectiveness over APAP in alleviating
fever and has the advantage of the antiinflammatory action that may be
beneficial in relieving symptoms
usually accompanied by fever such as
sore throat, muscle pain, or ear pain.
APAP and Ibuprofen
as Antipyretics
Abdullah Alalwan, PharmD Candidate
Acetaminophen (Tylenol®) and
ibuprofen (Advil®) are commonly used
Acetaminophen (also abbreviated as
APAP) works by inhibiting
prostaglandin synthesis and produces
antipyresis from inhibition of
hypothalamic heat-regulating center.
Onset of action for oral APAP is 1 hour.
The typical dose for infants and children
less than 12 years old is 10-15 mg/kg
given every four to six hours as needed
[do not exceed more than 5 doses (2.6
g) in 24 hours]. Adult dose is 325-625
mg every four to six hours as needed
-OR- 1000 mg three to four times daily
(do not exceed more than 4 grams). It is
also important to remember to counsel
patients on limiting APAP from all
sources (prescription and over the
counter) to < 4 grams daily. See Table 1
for a dosing chart based on age and
weight.
Alternating APAP and ibuprofen is a
treatment practice that is often
recommended to control fever. In this
practice, APAP or ibuprofen is given
and then followed by the other
antipyretic after four hours. During the
. . . . . . . . . . . . . . . . . . . . . . . .
The Family Practice Newsletter – December/January 2012-13
Acetaminophen Dosing (Oral)
Weight
(lbs)
6-11
12-17
18-23
24-35
36-47
48-59
60-71
72-95
> 95
Age
0 – 3 months
4 – 11 months
1 – 2 years
2 – 3 years
4 – 5 years
6 – 8 years
9 – 10 years
11 years
Adults
Ibuprofen Dosing (Oral)
Dose
40 mg
80 mg
120 mg
160 mg
240 mg
320 mg
400 mg
480 mg
325 – 650 mg Q4-6 hrs
or 1000 mg 3– 4x daily
Max Dose = 4 g/24 hrs
-OR- 2.6 g/24 hrs (pediatrics)
Weight
(lbs)
12-17
18-23
24-35
36-47
48-59
60-71
72-95
> 95
Age
< 6 months
6 – 11 months
1 – 2 years
2 – 3 years
4 – 5 years
6 – 8 years
9 – 10 years
11 years
Adults
Dose
50 mg
75 mg
100 mg
150 mg
200 mg
250 mg
300 mg
200 – 400 mg Q4-6 hrs
Max Dose = 2.4 g (adults)
-OR- 40 mg/kg (pediatrics)
Table 1 – APAP and Ibuprofen Dosing According to Age and Weight
Manufacturer recommends use of weight to select dose. If weight is not available, use age to select dose.
OTC dosing recommendations and strengths may vary by product and/or manufacturer!
alternating administration, the patient is
medicated every four hours by a
different antipyretic to ensure
continuous fever control and avoid
toxicity. Many studies state that
alternating APAP and ibuprofen has
better fever management and better
outcomes compared to monotherapy.
However, some studies recommend
against the alternating administration of
APAP and ibuprofen due to the lack of
clinical trials evaluating the safety of
such practice. Other studies recommend
using monotherapy in fever treatment as
it decreases the chance of dosing errors,
toxicity and possible adverse reactions.
In the studies that evaluated the adverse
effects of APAP and ibuprofen, there
were no significant adverse effects
related to both medications. Both
medications prove effectiveness in
treating febrile seizures although
ibuprofen has better efficacy than APAP
in decreasing fever.
References:
DWM: Driving While Medicated
1. Orriols L, Delorme B, Gadegbeku B, Tricotel A, Contrand B, et al. (2010) Prescription Medicines and the Risk of Road Traffic Crashes: A French RegistryBased Study. PLoS Med 7(11): e1000366. doi:10.1371/journal.pmed.1000366
2. National Highway Traffic Safety Administration (NHTSA). Impaired Driving Information. Accessed 11/15/2012. www.NHTSA.gov/impaired
Extended Indications for Rivaroxaban (Xarelto®) Use
1. Bauersachs R, Berowitz S, Brenner B, Buller H, Decousus H, Gallus A, et al. Oral rivaraoxaban for symptomatic venous thromboembolism. N Engl J Med.
2010;363:2499-510.
2. Buller H, Prins M, Lensing A, Decousus H, Jacobson B, Minar E, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J
Med. 2012;366:1287-1297.
3. LexiComp [database on the Internet]. Hudson (OH): Lexi-Comp, Inc. 2012 [cited 2012 Nov 15]. Available from: http://www.lexi.com.
4. U.S. Food and Drug Administration. FDA news release: FDA expands use of Xarelto to treat, reduce recurrence of blood clots. Available from:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm326654.htm. Updated: 2012 Nov 8. Accessed 2012 Nov 14.
APAP and Ibuprofen as Antipyretics
1. Merry, A., R. Gibs, J. Edward, G. Ting, C. Framptom, and E. Davies. "Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: A
randomized controlled trial." British Journal of Anesthesia 104: 80-88.
2. Van Esch A, Van Steensel-Moll H, Steyerberg E, Offringa M, Habbema J, and Derksen-Lubsen G. "Antipyretic efficacy of ibuprofen and acetaminophen in
children with febrile seizures." Arch Pediatr Adolesc Med (1995) 149(6):632-7
3. Hay A, Costelloe C, Redmond N, Montgomery A, Fletcher M, and Hollinghurst S. "Paracetamol plus ibuprofen for the treatment of fever in children
(PITCH): Randomised controlled trial." BMJ (2008) 2;337:a1302
4. Goldman, R., and D. Scolnik. "Underdosing of Acetaminophen by Parents and Emergency Department Utilization." Pediatric Emergency Care 20 (2004): 8993.
5. Ward, R., Bates B, Benitz W, Burchfield D, Ring D, Walls J et al. "Acetaminophen Toxicity in Children." American Academy of Pediatrics (2000)
6. Sarrell, E, Wielunsky E, and Cohen H. "Antipyretic Treatment in Young Children With Fever: Acetaminophen, Ibuprofen, or Both Alternating in a
Randomized, Double-blind Study." Arch Pediatr Adolesc Med 160.2 (2006): 197-202
. . . . . . . . . . . . . . . . . . . . . . . .
3