Idaho Medicaid Drug Utilization Review Program

1. Idaho Medicaid Drug Utilization Review Program 20 October 2011

2. Follow-up to Previous Reviews • Tramadol with SSRIs or SNRIs Potential for Serotonin Syndrome Pharmacy Provider Profiling • Colchicine DUR • Ketorolac DUR

3. Tramadol with SSRIs or SNRIsPotential for Serotonin SyndromePharmacy Provider Profiling • 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. • Letters along with the Serotonin Syndrome Informational sheet were sent to 182 pharmacies about 552 patients on 7/18/2011. • As of 9/27/2011, 45 responses have been received (25% response rate.)

4. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • Note that providers may choose more than one selection per response. • Reviewed and do not believe adjustment is needed 19 • Reviewed and have or will modify the treatment 10 • I have previously discussed with the provider and their response was 3 • I attempted to modify the therapy, but the patient response was not favorable 1

5. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • Note that providers may choose more than one selection per response. • Information clinically useful: plan to monitor 21 • I will use this information in the care of future pts 30 • No longer my patient 10 • Somewhat useful to my practice 8 • Extremely useful to my practice 8 • Very useful to my practice 23

6. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • “We are not a providing pharmacy for this patient.” • “The patient has been on concurrent therapy for several years with no apparent serotonic toxicity” • “Patients had a trial of Tramadol and other interacting meds since discontinued. Good reminder to watch for multiple offending drugs. This often gets over quickly on DURs.” • “John is no longer on tramadol. Only on it for a week.” • “I have previously discussed with the provider and their response was dosages not high enough to cause serotonin syndrome.” • “Patient and family counseled on serotonin syndrome. Patient has not filled medication since April (only need if pain).” • “Patient was taking Tramadol temporarily and hasn’t filled since. I have contacted providers several instances when they are adding Tramadol and they are currently taking 2 other serotonergic drugs. They always state they aren’t concerned about it.”

7. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • “Patient has addiction programs by past hydrocodone and has not responded to past antidepressant treatment. He has been on this therapy for 9 years, continue with current therapy.” • “Testing” • “Patient moved from this area Aug 15, 2011.” • “Both medications are prescribed by the same provider. Patient was counseled.” • “We explained the signs and symptoms of SS to the patient or caregiver if they get the symptoms they are to contact their prescriber. Our computer flags drugs.” • “Dr. switched Rx to Hydrocodone/APAP” • “Tramadol was changed to other pain relievers in May 2011. The patient is not symptomatic” • “Neither patient is currently taking tramadol at this time. The problem I find is the doctors are reluctant to change medication when you call them about a serotonin syndrome reaction. But refer to question 6.”

8. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • “7 of 12 required contact with the doctor” • “Patients are counseled to be aware of symptoms of Serotonin Syndrome. When taking more than one medication. Monitoring patient aware of interaction patient has been taking both Serotonergic drugs without problems. Will continue to remind patients of possible interaction with each refill. Helpful reminder reviewed with our pharmacist on staff also made copies of your hand out for educational purposes to give to patient at patient counseling.” • “Serotonin Syndrome is rare and I would rather have her take Tramadol than hydrocodone. I appreciate the service you are offering, however I do not think Serotonin Syndrome is common enough to warrant Medicaid contacting pharmacies. This one interaction would keep you busy for a very long time. Thank You.” • “I have counseled patient and she has been stable on both meds. She is aware of serotonin syndrome. Will f/u again.”

9. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • “Patient has had concomitant therapy since August 16 2010 and has not reported the symptoms of serotonin syndrome.” • “Not currently on this combination.” • “We do counsel on the possibility of SS.” • “Long standing regimen.” • “She has been consulted on the risk. She has been on Tramadol since April 2010. Cymbalta since 11/2010 without incident.” • “One patient no longer on Cymbalta. Other uses infrequently.” • “Thank you very much for bringing this to my attention. I will speak with the provider directly and report his or her response back to you.” • “To continue current regimen.” • “I have reviewed the information and plan to follow up with the prescriber concerning the treatment regimen for the specified patient.”

10. Tramadol with SSRIs or SNRIsPotential for Serotonin Syndrome Response detail as of 9/27/2011 • “She has been using this for awhile with no problem. I will let prescriber know of the issue again.” • “I have previously discussed with Doctor and he has been watching the patient sees no indication of symptoms of Serotonin Syndrome. He is aware and watching.” • “Continue therapy.” • “Counsel patient and combine with current med. Patient received full interaction consult.” • “Provider was notified about possible problems. No response.” • “Watch for symptoms, patients are not taking Tramadol all the time. Thanks.”

11. 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 Drugs-Compliance 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

12. 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®

13. Colcrys’® Place in Therapy • Utilization Overview All information based on Idaho Medicaid Pharmacy Data 2ndQuarter 2011 (4/1/11-6/30/11).

14. 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.

15. Therapeutic Criteria for Colcrys® • Acute Gout • Contra-indication and/or failure to NSAIDS or corticosteroids • Chronic Gout • Adjunct to allopurinol AND contra-indication or failure to NSAIDS

16. 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.

17. Ketorolac DUR • Patients were selected for evaluation if there was a paid claim for ketorolac > 40mg total daily dose or > 5 days duration 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 9/26/2011, 4 responses have been received (44% response rate)

18. 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.

19. Ketorolac DURResponse detail as of 9/26/2011 • Note that providers may choose more than one selection per response. • Information clinically useful: plan to monitor 2 • I will use this information for care of future patients. 2 • No longer my patient 1 • My patient, but I did not prescribe this 1 • My patient, but I have not seen him/her recently 1 • Somewhat useful to my practice 1 • “The meds were being given in the ER and PCP I believe” • “Will discuss Kadian and the use of other pain meds as an option for care”

20. 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 4 responses as of 9/26/2011

21. 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

22. Auto Refill Practices • Fax blast of survey went out to 318 pharmacies on July 8, 2011. • As of 10/3/2011 a total of 78 surveys have been returned (25% response rate)

23. Auto Refill Practices – Results • Does your pharmacy participate in an Auto Refill process?

24. Auto Refill Practices – Results • Do you exclude Auto Refill for any specific third party payers? If so which? ____See attached sheet for comments______

25. Auto Refill Practices – Results • How are specific patients included in the Auto Refill process?

26. Auto Refill Practices – Results • Which medications does your pharmacy include in your Auto Refill?

27. Auto Refill Practices – Results • Which medications does your pharmacy include in your Auto Refill? • Our Pharmacy has a list of excluded medications (please list), otherwise all are included in auto refill program 12 responses see attached sheet • Does your system automatically flag all medications or does each RX have to be individually flagged? 22 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? 20 responses see attached sheet • How many days remain on the prescription when your system Auto fills the medication? 46 responses average 5 days

28. Auto Refill Practices – Results • Does your system alert the patient that the prescription is ready for pick up? If so, how?

29. Auto Refill Practices – Results • How long does the medication sit on the shelf before it is returned to stock? • 39 responses with an average of 13 days • How does your store handle medications not picked up?

30. Auto Refill Practices – Results • Do you find the Auto Refill process beneficial for patients?

31. Auto Refill Practices – Results • Do you find the Auto Refill process potentially dangerous for patients?

32. Auto Refill Practices – Results • Do you find the Auto Refill process has increased compliance by the patient?

33. Auto Refill Practices – Results • Do you have any other comments related to the Auto Refill process? • 24 responses see attached sheet • Comments/Questions/Recommendations?

34. Hepatitis C DUR • Rationale for choosing this topic • Multiple ribavirin products are available at very different costs. • There is currently no therapeutic criteria required for ribavirin, so prescriptions pay at the pharmacy with prior authorization not needed.

35. Hepatitis C DUR – approximate cost of therapy for one month of therapy

36. Hepatitis C DUR • FDA Approved Indication • Treatment of chronic hepatitis C in combination with interferon. • Profiles Selected for Review • Patients who had at least one paid claim for oral ribavirin between 5/01/2011 and 7/31/2011. N=29 • Patient Demographics • 16 female, 13 male • Average age 46 yrs (Range 31-59)

37. Hepatitis C DUR • Diagnosis for Hepatitis C in Electronic Profile • Yes – 28 patients • No – 1 patient (but called prescriber and this patient does have hepatitis C) • Concomitant Therapy with Interferon • Defined as at least one fill for interferon between 5/01/2011 and 7/31/2011. Yes – all 29 patients • 7 of these patients are also on either Incivek or Victrelis for triple therapy.

38. Hepatitis C DUR • Medication Possession Ratio (MPR) • Definition: Total Days Supply of Dispensed Medication Total Days of Therapy • Example • e.g. Patient fills 30 tablets/30 days on January 1, March 1, and April 15 and then there are no more fills. • Total days of therapy: 31 (January) + 28 (February) + 31 (March) + 30 (April) + 14 (May) = 134 days • Note: last day of therapy is May 14th as patient has 30 days of medication to use from April 15 through May 14th. • MPR = 30 (Jan fill) + 30 (Mar fill) + 30 (Apr fill) = 90 = 0.67 134 days 134  • In general, MPR > 0.80 is considered good adherence to therapy. There are not specific standards for different drug classes. • If a patient fills prescriptions early (e.g. opioids), then MPR will be greater than 1.0

39. Hepatitis C DUR • Ribavirin MPR • Average for all 29 patients: MPR = 0.904 (average days of filled ribavirin = 126, average days of ribavirin therapy 142 days) • Subtracting out 8 patients with only one fill (who therefore had a MPR 1.0): Average MPR = 0.87 (average days of filled ribavirin = 163, average days of ribavirin therapy 186 days)

40. Hepatitis C DUR • Interferon MPR • Average for all 29 patients: MPR = 0.964 (average days of filled interferon = 138, average days of interferon therapy 145 days) • Subtracting out 7 patients with only one fill (who therefore had a MPR 1.0): Average MPR = 0.96 (average days of filled interferon = 173, average days of interferon therapy 182 days)

41. Hepatitis C DUR • Recommendations • Ribavirin and interferon do not currently require prior authorization. • All patients treated with oral ribavirin between May 1, 2011 and July 31, 2011 have a diagnosis of chronic hepatitis C and are on concomitant interferon therapy. • Therefore, prior authorization for oral ribavirin with therapeutic criteria is NOT recommended at this time.

42. Hepatitis C DUR • Potential for Cost Savings • Currently 26 out of 29 patients are using generic ribavirin 200mg tablets or capsules which are the most cost effective dosage forms. • Three (of the 26) of these patients switched from RibaPak to generic ribavirin during the time frame of this study. • Three patients are still using Ribapak or Ribasphere (400mg or 600mg) tablets.

43. Hepatitis C DUR • Cost Savings Example • Patient switched from using Ribapak 600-600 (two 600mg tablets) to using six ribavirin 200mg tablets daily [same daily dose of 600mg twice daily]. • Per 28 days of therapy: $1566 vs. $168 • Per year of therapy: $20,414 vs. $2190

44. Hepatitis C DUR • Incivek and Victrelis • New class of medications recently approved by the FDA – Protease Inhibitors for chronic hepatitis C • Triple combination with oral ribavirin and injectable interferon. Improves likelihood of attaining sustained virologic response (SVR).

45. Hepatitis C DUR • Incivek – triple therapy with ribavirin and interferon for 12 weeks followed by double therapy with ribavirin and interferon for an additional 12-36 weeks depending on viral response and prior response status. • Victrelis – triple therapy with ribavirin and interferon for 28-36 weeks with potential continuation of ribavirin and interferon through week 48 depending on viral response and prior response status

46. Hepatitis C DUR • In treatment-naïve patients, incidence of achieving SVR (ADVANCE study) • Triple therapy with Incivek – 79% • Standard ribavirin/interferon therapy – 46% • In treatment-naïve patients, incidence of achieving SVR (SPRINT-2 study) • Triple therapy with Victrelis – 66% • Standard ribavirin/interferon therapy – 38% • Cost of therapy per month: • Incivek $18,560 • Victrelis $4,984 • Currently requires prior authorization as a New Drug. • Initial approval for 12 weeks • Will be reviewed by P&T Committee in the future.

47. Hepatitis C DUR • Prior Authorization requests from the FDA approval date of Victrelis (5/13/2011) and Incivek (5/23/2011) were reviewed. • There were 17 approved requests. • 2 for Victrelis • 15 for Incivek • 2 patients never filled any prescriptions. • 1 for Victrelis • 1 for Incivek • Neither filled a prescription for ribavirin or interferon either. • All patients that filled prescriptions for Victrelis/Incivek also filled prescriptions for ribavirin and interferon for the same timeframe.

48. Hepatitis C DUR • Summary • Not recommending prior authorization for generic ribavirin • Recommend continuing to require prior authorization for Incivek and Victrelis

49. Transdermal Testosterone DUR • Rationale for this DUR Project • P&T Committee recommended implementing therapeutic criteria, including serum testosterone levels, for the Transdermal Testosterone drug class • Patient Selection • Patients with at least one paid claim for transdermal testosterone between June 1, 2010 and June 26, 2011 N=123 (122 male, 1 female with 1 fill)

50. Transdermal Testosterone DUR • Patient Demographics