21 July 2011
Follow-up to Previous Reviews
 Tramadol with SSRI’s or SNRI’s
 Potential for Serotonin Syndrome
 Thiazolidinedione (TZD) Safety
 Proton Pump Inhibitors
 Long Term Continuous Use
2
Tramadol with SSRI’s or SNRI’s:
Potential for Serotonin Syndrome
 Patients were selected if they had more than one tramadol fill, at





least a 30 day overlap with the SSRI or SNRI, and had both a
tramadol and an antidepressant claim within the most recent six
weeks of data.
179 patient profiles were evaluated.
Letters were sent to 174 prescribers about 94 patients on
2/21/2011.
Only prescribers of tramadol, SSRI, or SNRI received letters.
As of 7/5/2011, 42 responses have been received (24% response
rate.)
See packet for copy of the letter and the Serotonin Syndrome
Informational sheet.
3
Tramadol with SSRIs or SNRIs
Potential for Serotonin Syndrome
Response detail as of 7/5/2011
 Note that providers may choose more than one selection per response.
 Reviewed and do not believe adjustment is needed
 Reviewed and have or will modify the treatment
 Information clinically useful: plan to monitor
 I will use this information in the care of future pts
 No longer my patient
 My patient, but I did not prescribe this
 Somewhat useful to my practice
 Not useful to my practice
 Very useful to my practice
15
6
11
10
6
3
5
4
9
4
Tramadol with SSRIs or SNRIs
Potential for Serotonin Syndrome
Response detail as of 7/5/2011
 “We are actually tapering the tramadol. Used it as a way to stop opioid use.”
 “I was not aware that the patient was on tramadol.”
 “Thank You”
 “This patient did not report to me that she was on tramadol to the best of my memory.
She has since been fired from my office for med seeking behavior.”
 “Defer long term considerations to patient’s primary provider. I am an ER provider only
for this patient.”
 “tramadol has been discontinued”
 “Have already started taper and will be off in 30-60 days”
 “she is only taking tramadol 2 to 3 times a week and we are going to try to stop
completely. She is trying to take Excedrin for migraines. No new order for tramadol was
given at last visit.”
 “Review with supervising physician. Historically before I started seeing this patient. I
only provide follow up care at the facility this report is referring to. Often the patients
have been stable on their meds for quite some time and to make any changes could cause
decompensation. When possible I attempt to make reductions when appropriate. I will
still use the information provided as appropriate.”
5
Thiazolidinediones (TZD’s)
 Patients were selected for evaluation if there was a
paid claim for a TZD within the last three months.
 83 patient profiles were evaluated.
 Letters were sent to 65 prescribers about 63 patients
on 3/22/2011.
 As of 7/5/2011, 16 responses have been received (25%
response rate.)
 See packet for copy of the letter and FDA Drug Safety
Communication Insert.
6
Thiazolidinedione Safety
Response detail as of 7/5/2011
 Note that providers may choose more than one selection per response.
 Reviewed and do not believe adjustment is needed
2
 Reviewed and have or will modify the treatment
5
 Attempted to modify therapy unsuccessfully
1
 Information clinically useful: plan to monitor
5
 I will use this information in the care of future pts
3
 Previously saw this pt, but no longer in my care
2
 My patient, but I did not prescribe this
1
 Under my care, but have not seen recently
1
 Extremely useful to my practice
1
 Very useful to my practice
2
 Somewhat useful to my practice
3
 Not useful to my practice
1
 Will discontinue medication
1
7
Thiazolidinedione Safety
Response detail as of 7/5/2011
 “Patient was already on Avandia® and doing well prior to the drug label change and
guidelines state ok to use in patients already on this med. Patient did not want to change
then I will approach him again to consider change to Actos®”
 “I am already complying with the above and am no longer prescribing Avandia®”. Note
that prescriber also wrote in next to #8 that medication was reordered.
 “Control is poor with metformin. Patient is reluctant to try insulin at this time. Her
diabetes control is poor.”
 “Plan to modify therapy. Actos ®15mg every day”

“NO CHANGE”
 “Patient has been informed of risks and wishes to continue Avandia®”
 “Review with supervising physician. Historically before I started seeing this patient. I
only provide follow up care at the facility this report is referring to. Often the patients
have been stable on their meds for quite some time and to make any changes could cause
decompensation. When possible I attempt to make reductions when appropriate. I will
still use the information provided as appropriate.”
 “Will start Actos®”
8
Thiazolidinediones (TZD’s)
 Risk Evaluation and Mitigation Strategy (REMS)
 Rosiglitazone REMS Program


Approved 05/2011
Goals


To restrict access to rosiglitazone-containing medicines so that only
prescribers who acknowledge the potential increased risk of
myocardial infarction associated with the use of rosiglitazone are
prescribing rosiglitazone.
To restrict access to patients who have been advised by a healthcare
provider about the potential increased risk of myocardial infarction
associated with the use of rosiglitazone and are one of the following:


Either already taking rosiglitazone or
If not already taking rosiglitazone, they are unable to achieve glycemic
control on other medications and, in consultation with their healthcare
provider, have decided not to take pioglitazone for medical reasons
9
Thiazolidinediones (TZD’s)
 Risk Evaluation and Mitigation Strategy (REMS)
 Rosiglitazone REMS Program

Elements to Assure Safe Use




Healthcare providers who prescribe rosiglitazone-containing
medicines for outpatient or long-term care use are specifically
certified
Rosiglitazone will be dispensed only by specially certified pharmacies
 Medication will be mailed to the patient
Rosiglitazone will only be dispensed to patients with evidence or
other documentation of safe-use conditions
 Patient must review the Medication Guide and sign the Patient
Enrollment Form with their prescriber
Distributors will become certified and all rosiglitazone
medicines will be withdrawn from uncertified pharmacies
within 6 months after initial approval of the REMS
10
Thiazolidinediones (TZD’s)
 Risk Evaluation and Mitigation Strategy (REMS)
 Rosiglitazone REMS Program (Avandia-Rosiglitazone
Medicines Access Program™)
 www.avandia.com or
 Phone: 1-800-AVANDIA (1-800-282-6342)
 Fax: 1-888-772-9404
http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM255624.pdf
11
Proton Pump Inhibitors: Long Term
Continuous Use
 Patients were selected for evaluation if they had at
least 8 claims for a PPI over the six month period.
 167 patient profiles were evaluated.
 Letters were sent to 473 prescribers about 92 patients
on 4/11/2011 (19% lettering rate.)
 As of 7/5/2011, 113 responses have been received (24%
response rate.)
 See packet for copy of the letter and informational
sheet.
12
Proton Pump Inhibitors: Long Term
Continuous Use
Response detail as of 7/5/2011
 Note that providers may choose more than one selection per response.
 Reviewed and do not believe adjustment is needed
 Reviewed and have or will modify the treatment
 Attempted to modify therapy unsuccessfully
 Information clinically useful: plan to monitor
 Previously saw this pt, but no longer in my care
 Very useful to my practice
 Somewhat useful to my practice
 Not useful to my practice
 Will discontinue medication
 I am not the provider for this patient
 The information regarding this patient appears to be incorrect
27
19
10
21
23
16
16
17
3
14
6
13
Proton Pump Inhibitors: Long Term
Continuous Use
Response detail as of 7/5/2011
 “I agreed to refills but did not know how she had done eight refills in six months”
 “Patient has seen gastroenterologist and otolaryngologist who recommended the higher
dose.”
 “I was on call and covering for another provider”
 “The procedure ID on December 28 2010 is not mine. I never prescribed Omeprazole to
this patient. Please correct error”
 “Will review in closer detail her symptoms and discontinue of her PPI”
 “Prescribed this medication for this patient”
 “Previous NP saw this patient and she has left office”
 “Try to taper and use H2 blockers for breakthrough symptoms. Patient is intellectually
disabled and lives in a residential treatment center.”
 “Taper dose and uses H2 blockers for breakthrough. This patient has a diagnosis of
eosinophilic gastritis and is being monitored closely. He can purposely vomit if he is
upset for whatever reason possible anxiety. Very complex patient is intellectually disabled
and lives in a residential treatment center.”
14
Proton Pump Inhibitors: Long Term
Continuous Use
Response detail as of 7/5/2011
 “Chronic GERD”
 “Loves the medication and does not want to stop. Wonders if she can take medication
less often but continues. She will call back after receiving more information.”
 “Patient dismissed from clinic and care.”
 “I cared for this patient in the hospital but not as an outpatient.”
 “Getting to be annoying.”
 “I am not the prescriber.”
 “Increase GERD when off PPI.”
 “Someone else wrote Nexium”
15
Colchicine DUR
 Historical Perspective
 In June 2006, the FDA announced a new drug safety initiative
to remove unapproved drugs from the market, including a
final guidance entitled “Marketed Unapproved DrugsCompliance Policy Guide (CPG)”.


Notice that any illegally marketed product is subject to FDA
enforcement at any time
Clarified that the FDA intends to use a risk-based approach to
enforcement
 July 29, 2009: Colcrys® approved for Familial Mediterranean
Fever (FMF)
 July 30, 2009: Colcrys® approved for Acute Gout Flares
 October 16, 2009: Colcrys® approved for Chronic Gout
16
Colchicine DUR
 “Outraged Politicians Demand Gout Drug Price Probe”
 Article written June 10, 2011 for Medscape Medical News




Colcrys® granted 3 years marketing exclusivity
At time of approval, 21 companies were making oral colchicine
with costs as low as $0.04 per tablet. After approval Colcrys®
raised the price to $5 per tablet.
2 US Senators and 3 US Representatives are charging the
company with price gouging and are demanding an
investigation.
Concerns that this may be a new model for drug companies.
17
Colchicine DUR
 October 1, 2010: FDA sent out a notice that it intends to
initiate enforcement action against any marketed and listed
unapproved single-ingredient oral colchicine product that
is manufactured on or after November 15, 2010, or that is
shipped on or after December 30, 2010.
 Use of Colcrys®
Colcrys®
colchicine
May 2010
May 2011
No Rx’s
8 Rx’s
$241.82/46 tabs
42 Rx’s (7 different NDCs)
$23.25/46 tabs
No Rx’s
18
Colchicine DUR
 Cost Avoidance Calculations
 34 less colchicine prescriptions per month
 34 x $241.82 per Rx = $8221.88 per month
 Total cost avoidance of $98,662.56 per year
19
Colchicine DUR
 Definitions
 Gout is defined as an inflammatory arthritis induced by
the deposition of monosodium urate crystals in synovial
fluid and other tissues
 Hyperuricemia is defined as a serum urate level
≥ 6.8mg/dl, which is the limit of urate solubility at
physiologic temperature and pH
20
Colchicine DUR
 Epidemiology of Gout
 6.1 million adults in the US
 Prevalence increases with age
 Incidence higher in men than women (3-4:1 overall) although
decreases at older ages (at least partially due to declining
levels of estrogen which has uricosuric effects in women)
 Risk Factors: thiazide diuretics, cyclosporine, low dose aspirin
(<1000 mg/day), insulin resistance, metabolic syndrome,
obesity, renal insufficiency, hypertension, congestive heart
failure
 Dietary Risk Factors: meat, seafood, ethanol, soft drinks
21
Colchicine DUR
 Acute Gout Attack
 Sudden onset of severe debilitating pain with
progressive worsening over the first 24 hours
 Erythema and swelling in a joint
 Most attacks resolve within 3-10 days
 Management of Acute Gout
 Non-pharmacologic: joint rest and icing the affected site
 Pharmacologic – NSAIDS, corticosteroids, colchicine
22
Colchicine DUR
 Pharmacologic Treatment of Acute Gout Attack
 First line – NSAIDS, colchicine
 Relative efficacy of colchicine as compared with NSAIDS
is unknown
 In head-to-head studies between various NSAIDS, they
had similar benefits
 Alternative Agent – corticosteroids (all routes including
oral and intra-articular)
23
Colchicine DUR
 Treatment of Acute Gout Attack – NSAIDS
 Relative Contra-Indications: renal impairment, risk
factors for GI bleeding, congestive heart failure,
concomitant anticoagulant therapy
 Commonly used agents: indomethacin, naproxen,
sulindac
 Dose: Start as soon as possible (within 12-24 hours of
pain onset). High dose therapy for 2-3 days, then
decrease dose. Continue for at least 48 hours after
resolution of symptoms
24
Colchicine DUR
 Treatment of Acute Gout Attack – Colcrys®
 Dosage


First Day – 1.2mg at first sign of gout flare, followed by 0.6mg one
hour later
Subsequent Days – 0.6mg twice daily until flare subsides (typically
3-10 days)
 For mild (CrCl 50-80ml/min) to moderate (CrCl 30-50ml/min)
renal impairment, no dosage adjustment is needed, but the
patient should be monitored for adverse effects.
 For severe (CrCl < 30ml/min) renal impairment, a treatment
course should be repeated no more than once every 2 weeks. For
patients with gout flares requiring repeated courses,
consideration should be given to alternate therapy. For patients
undergoing dialysis, the total recommended dose for the
treatment of gout flares should be reduced to a single dose of
0.6mg (1 tablet).
25
Colchicine DUR
 Treatment of Acute Gout Attack – Corticosteroids
 Can be given orally, intravenously, intramuscularly,
intra-articularly

e.g. prednisone 20mg daily until symptoms resolve, generally
within 5-7 days (taper not necessary after short-term
treatment)
 Monoarticular attacks are often managed with the use of
intra-articular glucocorticoids.
26
Colchicine DUR
 Chronic Gout
 Chronic tophaceous gout



Polyarticular attacks
Symptoms between attacks
Crystal deposition (tophi) in soft tissues or joints
 Who to treat?

Patients with hyperuricemia who have at least two attacks per year or
tophi as determined by either clinical or radiographic methods
 When to treat?

Wait 1-2 weeks after the acute attack has subsided to begin chronic
treatment
 Goal of therapy


Uric Acid Level < 6mg/dl
Some patients may require Uric Acid level < 5mg/dl for resolution of
tophi
27
Colchicine DUR
 Management of Chronic Gout – Allopurinol
 Allopurinol is the drug of choice to lower serum uric
acid
 Mechanism of action

Xanthine oxidase inhibitor which blocks the synthesis of uric
acid
 Prior Authorization is not needed
 Dosage range is 100-800 mg daily (assess renal function)



Mild gout: 200-300 mg daily
Moderate gout: 400-600 mg daily
Severe gout: 700-800 mg daily
28
Colchicine DUR
 Management of Chronic Gout – Allopurinol, con’t.
 Patient has not failed allopurinol therapy if only on
300mg daily with normal renal function for severe gout
 Allopurinol dosing in renal impairment:



If CrCl 10-20ml/min, 200mg daily
If CrCl 3-10ml/min, 100mg daily
If CrCl <3ml/min, 100mg every other day
29
Colchicine DUR
 Management of Chronic Gout – Uloric®
 Uloric requires prior authorization
 Mechanism of Action – also a xanthine oxidase inhibitor
 No comparative studies done on efficacy between Uloric and
allopurinol
 Cost Comparison to allopurinol


#30 allopurinol 300mg - $7.16
#30 Uloric® 80mg - $168.24
 Therapeutic criteria for Uloric®
 Continuation of gout attacks after three months of allopurinol
therapy at a therapeutic dose (includes assessment of renal function)
 Serum urate levels > 6mg/dl after three months of allopurinol
therapy at a therapeutic dose
 Documented intolerance or allergy to allopurinol
30
Colchicine DUR
 Management of Chronic Gout – Colcrys®
 To prevent an acute attack as a result of starting
allopurinol, low dose NSAID (e.g. naproxen 250mg twice
daily) or prophylactic Colcrys® can be used.
 Duration of therapy:


Without tophi, prophylaxis with Colcrys® for 6 months
With tophi, optimal duration of therapy is unknown
31
Colchicine DUR
 Management of Chronic Gout – Colcrys®, con’t.
 Dose: Colcrys® 0.6mg orally once or twice daily


For mild (CrCl 50-80ml/min) to moderate (CrCl 3050ml/min) renal impairment, no dosage adjustment is
needed, but the patient should be monitored for adverse
effects.
For severe (CrCl < 30ml/min) renal impairment, the starting
doses should be 0.3mg per day and any increase in dose
should be done with close monitoring. For the prophylaxis of
gout flares in patients undergoing dialysis, the starting dose
should be 0.3mg given twice a week with close monitoring.
32
Colchicine DUR
 Management of Chronic Gout – Probenecid
 Mechanism of action – increases uric acid excretion by
blocking urate reabsorption
 Prior authorization is not needed
 Management of Chronic Gout – Krystexxa®
 Not covered by Idaho Medicaid outpatient prescription
drug program
 Pegylated urate oxidase enzyme – administered IV every
2 weeks by a healthcare professional due to the risk of
infusion reactions and anaphylaxis.
 Cost is $20,000 annually.
33
Colchicine DUR
 Pseudogout
 Deposition of calcium pyrophosphate crystals in joints
(rather than uric acid crystals).
 Causes arthritis characterized by sudden, painful
swelling in one or more joints, especially the knee.
 Drug of choice – NSAIDs
 Alternate drug – colchicine (if cannot use NSAID)
 Other treatments



Joint aspiration
Intra-articular corticosteroid
Joint rest
34
Colcrys’® Place in Therapy
 Utilization Overview
Number of
Recipients
Number of
Claims
Average
Cost/Claim
Allopurinol
172
432
$6.62
Colcrys®
16
29
$259.78
Probenecid
7
13
$25.26
Probenecidcolchicine
0
0
$0.00
Uloric®
9
25
$167.62
All information based on Idaho Medicaid Pharmacy Data 2nd Quarter 2011 (4/1/11-6/30/11).
35
Colchicine DUR
 Colcrys®


Patients were selected for evaluation if there was a
paid claim for Colcrys® over the six month period
11/1/2010-4/30/2011. A total of 21 patient profiles were
evaluated.
2 additional profiles were reviewed which had denied
PA requests for Colcrys®, but no paid claims.
36
Colchicine DUR
Patient Profiles Reviewed
9
8
8
7
6
Total # of
Patients
5
5
4
5
3
3
2
2
1
0
PA approved - Acute Gout
PA approved - Chronic Gout
PA approved - Other Diagnosis
PA denied
No PA submitted
37
Colchicine DUR
 Colcrys®
 Prior Authorization approved for 8 patients with acute
gout (*one patient failed both NSAID & corticosteroid)
5
4
Total # of
Patients
Failed NSAID*
4
NSAID contraindicated
3
2
1
0
2
2
Failed corticosteroid*
1
Acute attack while on
allopurinol
38
Colchicine DUR
 Colcrys®
 3 Prior Authorizations approved for Chronic Gout

Patients were already on allopurinol
 2 Prior Authorization approved for other Diagnosis


1 : vasculitis (approved for 3 month trial)
1 : Familial Mediterranean Fever (patient has been on
colchicine for years)
39
Colchicine DUR
 Colcrys®
 5 Prior Authorizations Denied

3 patients with paid Colcrys® claims previously (Colcrys®
would pay if there was a previous paid claim for colchicine in
the past 90 days. This AutoPA rule has since been removed.)
 2 patients with paid Colcrys® claims had chronic constipation
 1 patient has been on generic colchicine since 2005
 1 patient has been on generic colchicine since 2008 (please
refer to profile #16 in packet for further review)
 1 patient had diagnosis of pseudogout on prior authorization
form, but no other information was provided by the prescriber.
40
Colchicine DUR
 Colcrys®
 5 Prior Authorizations Denied (con’t.)

2 patients had no paid Colcrys® claims
 1 patient had “possible gout” with uric acid level of 6.6 mg/dl
and no contraindications to NSAIDS/corticosteroids
 1 patient was subsequently approved the following day when
the prescriber phoned into the call center with additional
information.
41
Colchicine DUR
 Colcrys®
 5 patients had at least one paid Colcrys® claim, but a
Prior Authorization request was never submitted


3 patients have no paid claims for any other gout medications
(NSAIDs, corticosteroids, allopurinol)
 Assumption would be off-label use
2 patients also on allopurinol
 Assumption would be gout diagnosis
42
Colcrys® - Summary
 72.2% (13/18) of the Prior Authorization requests
received were approved.
 Continue to require Prior Authorization for Colcrys®
with the current therapeutic criteria (listed on next
slide)
 Off-label use for treatment of chronic constipation was
discovered
 Turned off Auto Pay rule which approved Colcrys® at
point of sale if there was a paid colchicine claim in the
past 90 days.
43
Therapeutic Criteria for Colcrys®
Acute Gout
1.
•
Contra-indication and/or failure to NSAIDS or
corticosteroids
2. Chronic Gout
•
Adjunct to allopurinol AND contra-indication or
failure to NSAIDS
44
Colchicine DUR
 References
 Neogi, T. NEJM 2011;364(5):443-452.
 Management of Gout. Pharmacist’s Letter/Prescriber’s Letter November 2010, Volume




26, Number 261102.
Kelly, J. (2011, June 10). Outraged Politicians Demand Gout Drug Price Probe.
Retrieved from http://www.medscape.com/viewarticle/744408
Federal Register/ Vol.75, No. 190/ Friday, October 1, 2010/ Notices:60768-60771.
http://fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm227796.htm
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Enforcemen
tActivitiesbyFDA/SelectedEnforcementActionsonUnapprovedDrugs/ucm118990.htm
45
Ketorolac DUR
 Historical Perspective:
 Discovered that in the drug profiles the Maximum
Quantity was set at 10 tablets per day.
 The Maximum Quantity was immediately changed to 4
tablets per day as recommended by the package insert.
 Report was generated to see how many patients have
actually received doses higher than the recommended
amount and based on this report it was felt that a
Retrospective DUR would be appropriate.
46
Ketorolac DUR
 Black Box Warnings:
 WARNING


TORADOL ORAL (ketorolac tromethamine), a nonsteroidal anti-inflammatory drug
(NSAID), is indicated for the short-term (up to 5 days in adults) management of moderately
severe acute pain that requires analgesia at the opioid level and only as continuation
treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total
combined duration of use of TORADOL ORAL and ketorolac tromethamine should not
exceed 5 days.
TORADOL ORAL is not indicated for use in pediatric patients and it is NOT indicated for
minor or chronic painful conditions. Increasing the dose of TORADOL ORAL beyond a daily
maximum of 40 mg in adults will not provide better efficacy but will increase the risk of
developing serious adverse events.
 GASTROINTESTINAL RISK

Ketorolac tromethamine, including TORADOL, can cause peptic ulcers, gastrointestinal
bleeding and/or perforation of the stomach or intestines, which can be fatal. These events
can occur at any time during use and without warning symptoms. Therefore, TORADOL is
CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent
gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease
or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal
events.
47
Ketorolac DUR
 Black Box Warnings con’t.
 CARDIOVASCULAR RISK


NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial
infarction, and stroke, which can be fatal. This risk may increase with duration of use.
Patients with cardiovascular disease or risk factors for cardiovascular disease may be at
greater risk.
TORADOL is CONTRAINDICATED for the treatment of peri-operative pain in the setting of
coronary artery bypass graft (CABG) surgery.
 RENAL RISK

TORADOL is CONTRAINDICATED in patients with advanced renal impairment and in
patients at risk for renal failure due to volume depletion.
 RISK OF BLEEDING


TORADOL inhibits platelet function and is, therefore, CONTRAINDICATED in patients with
suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis,
incomplete hemostasis and those at high risk of bleeding.
TORADOL is CONTRAINDICATED as prophylactic analgesic before any major surgery.
48
Ketorolac DUR
 Black Box Warnings con’t.
 RISK DURING LABOR AND DELIVERY

The use of TORADOL in labor and delivery is contraindicated because it may adversely affect
fetal circulation and inhibit uterine contractions. The use of TORADOL is contraindicated in
nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs
on neonates.
 CONCOMITANT USE WITH NSAIDS

TORADOL is CONTRAINDICATED in patients currently receiving aspirin or NSAIDs
because of the cumulative risk of inducing serious NSAID-related side effects.
 SPECIAL POPULATIONS


Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs) of
body weight and for patients with moderately elevated serum creatinine.
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c0336606-7366-41ce-9cef-aa6524b92b11
49
Ketorolac DUR
 Patients were selected for evaluation if there was a
paid claim for ketorolac > 40mg total daily dose over
the 3 month period 3/1/2011-5/31/2011.
 A total of 29 patient profiles were evaluated
 Letters were sent to 9 prescribers about 9 patients on
6/20/2011.
 As of 7/7/2011, 3 responses have been received (33%
response rate)
50
Ketorolac DUR
 Criteria Paragraph
 During a retrospective drug utilization review, it was noted that your
patient, (Patient Name), received at least one prescription of more than 20
tablets and/or received multiple consecutive fills of ketorolac. The
recommended maximum daily dose of oral ketorolac is 40mg per day (10mg
tablet four times daily). Ketorolac is FDA approved for the short term (up
to 5 days) management of moderately severe acute pain that requires
analgesia at the opioid level and only as continuation treatment following
IV or IM dosing of ketorolac. The total combined duration of use of
injectable and oral ketorolac should not exceed 5 days. Increasing the dose
beyond the recommended daily maximum of 40mg will not provide better
efficacy, but will increase the risk of developing serious adverse events.
Ketorolac has black box warnings addressing the following risks:
Gastrointestinal, Cardiovascular, Renal, Risk of Bleeding, Risk During
Labor and Delivery, Concomitant Use with NSAIDs, and in Special
Populations.
51
Ketorolac DUR
 20 patients who did not receive a letter had only one fill
≤ 20 tablets in six months. These claims paid at point of
sale with no Prior Authorization needed.
16
14
14
15 tabs/3 days
12
10 tabs/2 days
10
Total # of
Patients
15 tabs/2 days
8
20 tabs/4 days
6
4
2
14 tabs/3 days
2
20 tabs/3 days
1
1
1
1
0
52
Ketorolac DUR
 There was a total of 9 patients who did receive a letter.
These claims also paid at point of sale with no Prior
Authorization needed.
5
4
4
Total # of
Patients
3
2
1
30 tabs/7 days
3
2
30 tabs/5 days
2-11 Rx's filled - see next
slide for details
0
53
Ketorolac DUR
 Breakdown of 4 patients with multiple fills:
 Patient 1 – 30 tabs/5 days (Dec 6, Dec 20, Feb 13, & Apr
16)
 Patient 2 – 30 tabs/7 days (Dec 10, Feb 28, & May 11)
 Patient 3 – 40 tabs/20 days (Feb 23) & 15 tabs/3 days (Apr
22)
 Patient 4 – 11 fills of 15 tabs/3 days (Jan 12, Feb 10, Feb 25,
Mar 6, Mar 15, Mar 29, Apr 6, Apr 11, Apr 22, May 5, &
May 11)

Please refer to patient’s profile in packet for detailed profile
54
Ketorolac DUR
Response detail as of 7/7/2011
 Note that providers may choose more than one selection per response.
 Information clinically useful: plan to monitor
 I will use this information for care of future patients.
 No longer my patient
 My patient, but I did not prescribe this
 My patient, but I have not seen him/her recently
 Somewhat useful to my practice
1
1
1
1
1
1
 “The meds were being given in the ER and PCP I believe”
55
Ketorolac DUR - Summary
 Maximum quantity per day reduced from 10 to 4
tablets on 5/24/2011
 DUR letter sent on 6/20/2011 to 9 prescribers with 3
responses as of 7/7/2011
56
Tramadol with SSRIs or SNRIs
Potential for Serotonin Syndrome
Pharmacy Provider Profiling
 Profiles are being generated and are currently in the
process of being sent out along with the Serotonin
Syndrome Handout.
 New Response form created to be more relevant to
Pharmacists. (Please see form in Packet as well as new
prescriber response form).
57
Proposed Studies for Next Quarter:
 Analysis of Auto Refill Practice
 Atypical Antipsychotics: Impact of P&T Recommendations
 High Dose Utilization through multiple strengths of
selected medication
 Atypical Antipyschotics
 Focalin XR®
 Injectable Atypical Antipsychotics
 P&T Committee Narcotic Analgesic Studies
 Further discussed in following slides
58
Proposed Studies for Next Quarter:
 Synagis 2010-2011 Season
 Update on the impact of using the 2009 revised
American Academy of Pediatrics (AAP)
recommendations for infants with gestational age
between 32 to 35 weeks.
 Ribavirin
 Only FDA approved for treatment of hepatitis C with
concomitant interferon.
 Leukotrienes vs. inhaled corticosteroids in children with
asthma
59
Auto Refill Practices
Some pharmacies are instituting Auto Refill policies
which allow them to automatically dispense refills
based on days since last fill
 Issues
 Potential for stockpiling
 Potential for continued fill of discontinued medications
 Increase cost/waste
 Please see Survey in Packet
60
Auto Refill Practices
 Fax blast of survey went out to 318 pharmacies on July
8, 2011.
 As of 7/11/2011 a total of 48 surveys have been returned
(15% response rate)
61
Auto Refill Practices – Results


Does your pharmacy participate in an Auto Refill process? Yes __16___ No __32___
Do you exclude Auto Refill for any specific third party payers? Yes __4___ No __16___


How are specific patients included in the Auto Refill process?





__0___ All patients are automatically enrolled in Auto Refill
__12___ All patients are offered Auto Refill as a service option
__7___ A patient must specifically request Auto Refill
__1___ All patients are included unless they specifically “opt out” of the program
Which medications does your pharmacy include in your Auto Refill?







If so which? ____See attached sheet for comments______
__2___ All medications
__14___ Maintenance medications only
__1___ Our Pharmacy has a specific list of medications or therapeutic classes (please list) see attached sheet
Our Pharmacy has a list of excluded medications (please list), otherwise all are included in auto refill program
7 responses see attached sheet
Does your system automatically flag all medications or does each RX have to be individually flagged? 14
responses see attached sheet
Do you have a systematic method to discontinue an Auto Refill to prevent duplication of therapy when drugs or
doses change? 12 responses see attached sheet
How many days remain on the prescription when your system Auto fills the medication? 12 responses
average 5 days
62
Auto Refill Practices - Results

Does your system alert the patient that the prescription is ready for pick up? Yes __16__ No __5__
if so, how?






How long does the medication sit on the shelf before it is returned to stock? 27 responses
average 14 days
How does your store handle medications not picked up?




Comments? See attached sheet
Do you find the Auto Refill process has increased compliance by the patient? Yes __12___ No __2___


Comments? See attached sheet
Do you find the Auto Refill process potentially dangerous for patients? Yes __11___ No __7___


__22___ Phone call to patient
__6___ Mail out
__9___ Other
Do you find the Auto Refill process beneficial for patients? Yes __14___ No __4___


__16___ Phone
__10___ Text
__10___ Email
__2___ Other (comments for both – manual call or delivery or mail)
Comments? See attached sheet
Do you have any other comments related to the Auto Refill process? 24 responses see attached sheet
63
Atypical Antipsychotics
P&T Recommendations
 Approved for diagnosis per FDA indications or off-label indications





with supporting evidence-based literature.
All patients receiving at least 90 days of therapy for the past 120 days as
of implementation date will be grandfathered. No criteria for diagnosis
required.
No PDL requirements for patients with schizophrenia and related
psychosis.
Bipolar, major depression adjunctive, autism and other designated
acceptable diagnoses will require failure of a preferred agent for
designated non-preferred agents.
Age, dose and quantity per labeling information on all drugs.
If the medical diagnosis and required drug history have been
submitted as prior claims then the prescription will auto-approve at
point of sale. i.e. No written PA required.
64
Atypical Antipsychotics
P&T Recommendations
Agent
Diagnoses/Criteria
Abilify®
Schizophrenia and Related Psychoses; Bipolar
Disease; Autism; Adjunctive Therapy in Major
Depression with continuous antidepressant therapy
within the last eight weeks with trials of a minimum
of two different antidepressants with a minimum
trial of two weeks each.
Abilify® Injectable
Schizophrenia and Related Psychoses with Acute
Agitation; Bipolar Disease with Acute Agitation
Clozapine
Resistant Schizophrenia and Related Psychoses
Fanapt®
Schizophrenia and Related Psychoses
Geodon®
Schizophrenia and Related Psychoses; Bipolar
Disease – Mania and Mixed State
Geodon® Injectable
Schizophrenia and Related Psychoses with Acute
Agitation
65
Atypical Antipsychotics
P&T Recommendations (continued)
Agent
Invega®
 Adherence
Diagnoses/Criteria
RatesSchizophrenia and Related Psychoses
Invega Sustenna®
Schizophrenia and Related Psychoses AND
History of Oral Invega® or Risperidone within
the past 2 years AND
Failure of Risperdal Consta®
Risperidone
Schizophrenia and Related Psychoses; Bipolar
Disease – Mania and Mixed State; Autism; Disruptive
Behavioral Disorders; Obsessive Compulsive
Disorder
*Brand name will deny for brand/generic rule
Risperdal Consta®
Schizophrenia and Related Psychoses
Saphris®
Schizophrenia and Related Psychoses; Bipolar
Disease – Mania and Mixed State
66
Atypical Antipsychotics
P&T Recommendations (continued)
Agent
Seroquel®
 Adherence
Diagnoses/Criteria
RatesSchizophrenia and Related Psychoses ; Bipolar
Disease – Mania and Mixed State; Bipolar
Depression; Obsessive Compulsive Disorder
Seroquel XR®
Schizophrenia and Related Psychoses ; Bipolar
Disease – Mania and Mixed State; Bipolar
Depression; Adjunctive Major Depression
Continuous - antidepressant therapy within the last
eight weeks with trials of a minimum of two different
antidepressants with a minimum trial of two weeks
each.
Symbyax®
Treatment Resistant Depression - Continuous
antidepressant therapy within the last eight weeks
with trials of a minimum of two different
antidepressants with a minimum trial of two weeks
each.
67
Atypical Antipsychotics
P&T Recommendations (continued)
Agent
Zyprexa®
 Adherence
Diagnoses/Criteria
RatesSchizophrenia and Related Psychoses, Acute
Agitation; Bipolar, Acute Agitation
Zyprexa Injection®
Schizophrenia and Related Psychoses; Bipolar
Disease, Acute Agitation
Zyprexa Relprevv®
Reimbursed as Medical Benefit Only; Schizophrenia
and Related Psychoses
68
Atypical Antipsychotics
P&T Recommendations
Patients Receiving Atypical Antipsychotics
35%
65%
With Approvable
Diagnosis
Without Approvable
Diagnosis
All information based on Idaho Medicaid Pharmacy Data 1st Quarter 2011
(1/1/11-3/31/11).
69
High Dose Atypical Antipsychotics
417 recipients received multiple doses of the same atypical antipsychotic
during April, May, June 2011
Product Distribution by Number of Recipients
Multiple Doses of Same Agent
1
184
SYMBYAX
1
17 30
FANAPT
INVEGA
CLOZAPINE
59
62
ABILIFY
GEODON
109
77
ZYPREXA
RISPERIDONE
SEROQUEL
All information based on Idaho Medicaid Pharmacy Data 2nd Quarter 2011 (4/1/11-6/30/11).
70
High Dose Focalin XR®
16
15
14
12
12
# of patients
on multiple
strengths
10
10
8
6
4
2
0
Apr-11
May-11
Jun-11
4 patients had multiple strengths each month over the 3 month period
71
Injectable Atypical Antipsychotics
Invega® Sustenna® and Risperdal® Consta®
 Indications
Agent
Indication
Invega® Sustenna®
Acute and Maintenance Treatment of Schizophrenia
Risperdal® Consta®
Treatment of Schizophrenia
Risperdal® Consta®
Mono or Adjunct therapy to Lithium or Valproate in
Bipolar I Disorder
 Utilization Overview
Agent
Recipients
Invega® Sustenna®
106
Risperdal® Consta®
148
Oral Agents
6936
Patients Receiving Both Oral and Injectable – 1st Quarter 2011
148
*Idaho Medicaid Data 4th Quarter 2010 (10/1/2010-12/31/2010)
72
Injectable Atypical Antipsychotics
Invega® Sustenna® and Risperdal® Consta®
 Responsibilities of the parties involved
 Magellan

Run reports to identify Prescribers, Pharmacies, and Patients
 Idaho Medicaid Pharmacy Unit

Analyze reports and identify where intervention is needed
 Idaho Medicaid Program Integrity

Send out letters requesting documentation of dose
administration
73
P&T Committee Narcotic Analgesic
Studies
 Committee Recommendation for Drug Utilization
Review of Narcotic Analgesics
 The Committee recommended a comprehensive drug utilization review of
short and long-acting narcotics. This was based on concern over the
misuse/abuse of these agents that is not addressed through the preferred
drug list. Components of the proposed review are outlined below.
 Patient Profiling
 Number of patients on monthly (chronic) narcotics
 Number of different agents used by individual patients
 Total (cumulative) monthly doses of all concurrent narcotics
 Number of prescribers per patient
 Analysis of multiple scripts from multiple providers
74
P&T Committee Narcotic Analgesic
Studies
 Patient Profiling Continued
 Other addictive drugs prescribed concurrently
 Diagnosis/indication for narcotic use and data backing that
diagnosis
 Patients with no relevant diagnosis for medication
 Evaluation for evidence of illicit drug use
 Relationships of long-acting narcotic use and breakthrough
narcotics use (lack of long acting and/or breakthrough
narcotics given continuously)
 Hospital and ER admissions for overdose
 Prescription fill history, including early refills
75
P&T Committee Narcotic Analgesic
Studies
 Provider Profiling
 Prescribing pattern for non-pain clinic prescribers
 They also suggested utilizing several data sources outside
Medicaid including outlier reports from the Board of
Pharmacy Prescription Drug Monitoring Program,
legal/arrest databases and hospital discharge medication
records.
76
P&T Committee Narcotic Analgesic
Studies
 Possible policy changes suggested for consideration after
collection and analysis of the data



Restriction of prescriptions to prescribers and pharmacies within
Idaho state borders
Stricter refill policies (90% rather than current 75% threshold)
Expansion of lock-in program
77
P&T Committee Narcotic Analgesic
Studies
 DUR Board Suggestions
 Propose doing one study per quarter?
 What studies would be most beneficial?
 What studies would be feasible?
 Recommendations?
78
Synagis Utilization Intervention
 Update using the 2010-2011 RSV season data on the
impact of using the 2009 revised American Academy
of Pediatrics (AAP) recommendations for infants with
gestational age between 32 to 35 weeks.
 Profiles will be reviewed to assess outcomes
Ribavirin
 Generic ribavirin vs. Ribapak®
 Review patient profiles to determine if patients have a
diagnosis of hepatitis C and are concomitantly on
interferon.
80
Prospective DUR Report
 History Errors:
• DD – drug-to-drug
• PG – drug to pregnancy
• TD – therapeutic duplication
• ER – early refill
• MC – drug-to-disease
 Non-History Errors:
• PA – drug-to-age
• HD – high dose
• LD – low dose
• SX – drug-to-gender
81
Early Refill Edits
Specific Therapeutic
Description
Medications
# of (all)
claims
# of paid
claims
ANALGESICS, NARCOTICS
morphine, codeine, oxycodone, etc.
2,254
246
ANTICONVULSANTS
carbamazepine, phenytoin, gabapentin, etc.
1,041
180
ANTI-ANXIETY DRUGS
benzodiazepines
771
131
ANTIPSY, ATYP, DOP, & SERO, ANTAG
Saphris®, Clozaril®, Fanapt®, Zyprexa®, Latuda®, Seroquel®, Invega®,
Risperdal®, Geodon®
484
70
SEROTONIN SPEC REUPTAKE INHIB(SSRI)
Celexa®, Lexapro®, Prozac®, etc.
398
37
ANTI-NARCOLEPSY/ANTI-HYPERKINESIS
Nuvigil®, Provigil®, Focalin®, Daytrana®, methylphenidate
294
25
PROTON-PUMP INHIBITORS
Nexium®, omeprazole, Aciphex®, etc.
275
40
BETA-ADRENERGIC AGENTS
albuterol, salmeterol, formeterol, etc.
233
35
ADRENERG.,AROMAT.,NON-CATECHOLAMINE
amphetamines (Adderall®, Vyvanse®)
221
27
HYPOTENSIVES, SYMPATHOLYTIC
clonidine, guanfacine, etc.
204
40
82
DUR Summer Newsletter
 Copy of Spring Newsletter in packet
 Brainstorm for new topics
83
Medicaid Update
84