Idaho Medicaid Drug Utilization Review Program

1. Idaho Medicaid Drug Utilization Review Program 14 April 2011

2. Follow-up to Previous Reviews • Long Acting Beta Agonist Inhalers • Lack of Prior Controller Use • Long Acting Beta Agonist Inhalers with High Rescue Inhaler Use • Fentanyl Patch Frequency < 72 Hours

3. Long Acting Beta Agonist Inhalers: Lack of Controller Use • Letters sent if patient had at least one fill of a LABA during the 3 month period that ended on 9/30/2010. History was evaluated for long term continuous use of a LABA and lack of a controller medication if applicable. Results: • 150 patient profiles were evaluated. • Letters were sent to 32 prescribers about 30 patients on 12/16/2010 (21.3% lettering rate.) • As of 3/31/2011, 9 responses have been received (28% response rate.) • See packet for copy of the letter .

4. Long Acting Beta Agonist Inhalers: Lack of Controller Use: Response detail as of 3/31/2011: • Note that providers may choose more than one selection per response. • Reviewed and do not believe adjustment is needed 3 • Reviewed and have or will modify the treatment 2 • Information clinically useful: plan to monitor 2 • I will use this information in the care of future pts 2 • No longer my patient 1 • My patient, but I did not prescribe this 2 • Somewhat useful to my practice 4 • Not useful to my practice 2 • Information appears to be incorrect 1

5. Long Acting Beta Agonist Inhalers with High Rescue Inhaler Use • Patients were selected for evaluation if they had at least one fill of a LABA during the 6 month period and at least 2 fills for a SABA in the period that ended on 10/30/2010. • 208 patient profiles were evaluated. • Letters were sent to 399 prescribers about 102 patients on 12/28/2010 (192% lettering rate.) • As of 3/31/2011, 119 responses have been received (30% response rate.) • See packet for copy of the letter.

6. SABA overuse in LABA patients: Response detail as of 1/1/2011: • Note that providers may choose more than one selection per response. • Reviewed and do not believe adjustment is needed 21 • Reviewed and have or will modify the treatment 23 • Attempted to modify therapy unsuccessfully 7 • Information clinically useful: plan to monitor 25 • I will use this information in the care of future pts 8 • Not my patient 8 • Previously saw this pt, but no longer in my care 14 • My patient, but I did not prescribe this 31 • Under my care, but have not seen recently 9 • Extremely useful to my practice 8 • Very useful to my practice 20 • Somewhat useful to my practice 11 • Not useful to my practice 1o • Information appears to be incorrect 2 • Will discontinue medication 1 • Will change dose 6

7. Fentanyl Topical Patch (Duragesic®): Frequency of Administration Patients were selected for evaluation if they received more than 10 patches in a 30 day period during the 3 month period that ended on 11/30/2010. 291 patient profiles were evaluated. Letters were sent to 60 prescribers about 44 patients on 12/28/2010 (21% lettering rate.) As of 3/31/2011, 29 responses have been received (48 % response rate.) See packet for copy of the letter.

8. Fentanyl Patch Frequency of Administration: Response detail as of 1/1/2011: • 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 4 • Attempted to modify therapy unsuccessfully 4 • Information clinically useful: plan to monitor 2 • Previously saw this pt, but no longer in my care 3 • Very useful to my practice 2 • Somewhat useful to my practice 2 • Will change dose 1

9. Quetiapine (Seroquel® ) is an atypical antipsychotic with the following indications and recommended doses Low Dose Quetiapine Utilization * Clinical studies indicate that the antipsychotic effect occurs in the range of 600-800mg

10. Seroquel® Dosage Dosage Strengths Available: 25mg, 50mg, 100mg, 200mg, 300mg, 400mg Legitimate Use of Lower Strengths • Initial dose titration (approximately 5 days) • Dose adjustments • Dose individualization not covered by single strength tablets Use of Concern • Off label use for insomnia

11. Use of Quetiapine for Insomnia • Used at doses considered sub-therapeutic for schizophrenia or bipolar disorder • Used for insomnia in patients who do not have co-morbid psychosis • Not FDA-Approved • Not supported by available clinical evidence • Exposure of patients to adverse metabolic effects including weight gain, hyperglycemia, overt diabetes and adverse lipid profiles • More costly than traditional hypnotics

12. Idaho Medicaid DUR Study April 2008 • Reviewed Medicaid Claims 1/2006 thru 12/2007 • Identified patients using all AAPs at a low dose without schizophrenia, bipolar disorder or childhood psychosis/developmental disorders • Low dose quetiapine defined as < 300 mg/day • 395 patients identified as being on low dose quetiapine without above designated diagnoses (10% of claims) • Educational leaflets distributed

13. Current Utilization of Low Dose Quetiapine • Evaluated number of recipients receiving quetiapine 50 mg/day or less for more than 30 days for time period of 4/1/10-3/31/11 • 130 recipients receiving <25 mg daily • 525 recipients receiving >25mg & <50mg daily • Total cost was $378,994 • 28% of all quetiapine patients were getting <50mg/day

14. Current Utilization of Low Dose Quetiapine by Gender Information based on Idaho Medicaid Claims most recent 12 months (4/1/10-3/31/11)

15. Current Utilization of Low Dose Quetiapine by Age

16. Proposal for PA Criteria • Quetiapine cumulative daily doses of < 100 mg will be automatically approved only for new starts for a maximum of 15 days. (add all dosage strengths) • All other uses including dose titration in existing patients will require prior authorization review

17. Current Intervention/Outcome Studies • Tramadol with SSRI’s or SNRI’s • Potential for Serotonin Syndrome • Thiazolidinedione (TZD) Safety • Proton Pump Inhibitors • Long Term Continuous Use

18. Serotonin Syndrome • Potentially life-threatening reaction to an elevation of serotonin in the body. Agents that block the reuptake of serotonin, slow breakdown, or increase release can contribute to development of the syndrome. • Resolves quickly with appropriate treatment, including discontinuation of related medication. • Frequently undiagnosed due to lack of awareness and the wide range of medications that can cause Serotonin Syndrome.

19. 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 3/31/2011, 39 responses have been received (22% response rate.) • See packet for copy of the letter and Serotonin Syndrome Informational sheet.

20. Tramadol with SSRI’s or SNRI’s: Potential for Serotonin Syndrome

21. Tramadol with SSRI’s or SNRI’s: Potential for Serotonin Syndrome

22. Tramadol with SSRI’s or SNRI’sCriteria Paragraph • Tramadol (Ultram®) is a centrally acting synthetic opioid which also inhibits the reuptake of both serotonin and norepinephrine. Therefore, serotonin syndrome can occur when tramadol is used concomitantly with serotonergic drugs such as Selective Serotonin Reuptake Inhibitors (SSRIs) [examples: citalopram, escitalopram, fluoxetine, paroxetine, and sertraline] and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) [examples: venlafaxine, duloxetine and desvenlafaxine]. During a recent review, it was noted that your patient, Recipient Name, is receiving tramadol and a SSRI or SNRI. The specific SSRI or SNRI product is noted in the attached profile. Please review the attached profile and monitor this patient for potential serotonin syndrome and adjust medications if clinically appropriate (e.g. use a different analgesic agent). Please refer to the attached educational leaflet for signs and symptoms of serotonin syndrome as well as a listing of additional drugs that can precipitate serotonin syndrome.

23. Tramadol with SSRI’s or SNRI’s: Response detail as of 3/31/2011: • Note that providers may choose more than one selection per response. • Reviewed and do not believe adjustment is needed 15 • Reviewed and have or will modify the treatment 4 • Attempted to modify therapy unsuccessfully 3 • Information clinically useful: plan to monitor 10 • Will use this information in care of future patients 8 • Not my patient, never has been 2 • Previously saw this pt, but no longer in my care 5 • Patient under my care, but not seen recently 3

24. Tramadol with SSRI’s or SNRI’s: Response detail as of 3/31/2011 (continued): • Extremely useful to my practice 3 • Very useful to my practice 7 • Somewhat useful to my practice 5 • Not useful to my practice 4 • Will discontinue medication 2 • Will change dose 3 • Other 5

25. Tramadol with SSRI’s or SNRI’s: Comments of Interest* • Profile ID: 0001584482: I was not aware the patient was on tramadol. • Profile ID: 0000022513: Defer long term considerations to patient’s primary provider. I am ER provider for this patient. * Profile is in member packet for your review

26. Thiazolidinediones • Troglitazone – removed from market 1999 due to adverse hepatic effects • Pioglitazone hydrochloride (Actos ®) – initial approval 1999 • Pioglitazone + metformin (Actoplus Met®, Actoplus Met XR®) • Pioglitazone + glimepiride (Duetact ®) • Rosiglitazone maleate (Avandia®) – initial approval 1999 • Rosiglitazone + metformin (Avandamet ®) • Rosiglitazone + glimepiride (Avandaryl ®) Plasma glucose is lowered through PPAR gamma receptors • Liver • Heart • Adipose tissue • Skeletal muscle • Kidney vascular and gut endothelial cells

27. TZD Adverse Effects • Risk of Heart Failure OR 1.32-2.18 • Pio and Rosi • Risk of Edema OR 2.26-4.62 • Pio and Rosi • Fractures in Women OR 2.23 • Pio and Rosi • Increased all-cause or cardiovascular mortality • Rosiglitazone • No evidence with pioglitazone • Some studies suggest reduced risk of all-cause and CV mortality with pioglitazone

28. Regulatory Decisions on Rosiglitazone September 2010 The FDA required GSK to implement a restricted access program for rosiglitazone and combination products that contain rosiglitazone • Labeling changes • REMS implementation • Cease global marketing and promotion • Independent re-assessment of RECORD study • Suspension of TIDE study European Medicines Agency announced suspension of marketing authorization in Europe

29. Risk Evaluation and Mitigation Strategy (REMS) Restricted Access (added to labeling 2/4/11) • Patients already receiving and benefitting • New patients not controlled with other anti-diabetic medications and unable to take or do not wish to use pioglitazone Documentation • Prescribers: attest and document patient eligibility • Patients: consent form acknowledging review and understanding of risks REMS to be approved Spring 2011 with implementation within 6 months

30. Thiazolidinediones (TZDs) • Safety issues with Avandia® related to increased risk for Cardiovascular Events. • “The U.S. Food and Drug Administration announced that it will significantly restrict the use of the diabetes drug Avandia® (rosiglitazone) to patients with Type 2 diabetes who cannot control their diabetes on other medications. These new restrictions are in response to data that suggest an elevated risk of cardiovascular events, such as heart attack and stroke, in patients treated with Avandia®.” http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm226956.htm

31. 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 3/31/2011, 29 responses have been received (48% response rate.) • See packet for copy of the letter and FDA Drug Safety Communication Insert.

32. TZD – Concurrent Medications Other Concurrent Diabetes Medications Monotherapy 11 1 other 29 2 other 17 3 other 9 Specific Drugs Used in Combo with Avandia® Metformin 48 Sulfonylurea 18 Insulin 8 Meglitinide 2 Incretin Mimetic 1

33. TZD – Other Observations • Adherence issues noted in 13 patients • Number of Prescribers • Single 49 • Two 13 • Three 4 • Number of Pharmacies • Single 62 • Two 4

34. TZD’sCriteria Paragraph Your patient, Recipient Name, has received at least one recent prescription for rosiglitazone. The FDA has notified healthcare professionals and patients that information on the cardiovascular risks (including heart attack) of rosiglitazone has been added to the product labeling and patient Medication Guide. This information was first announced by the FDA on September 23, 2010 as part of new restrictions for prescribing and use of this drug.   In addition to describing the cardiovascular risks, the drug labels for Avandia, Avandamet, and Avandaryl have been revised to state that rosiglitazone and rosiglitazone-containing medicines should only be used: - In patients already being treated with these medicines - In patients whose blood sugar cannot be controlled with other anti-diabetic medicines and who, after consulting with their healthcare professional, do not wish to use pioglitazone-containing medicines (Actos®, Actoplus Met®, Actoplus Met XR®, or Duetact®).   Please read the attached FDA Drug Safety Communication. A link to the FDA complete safety information is included below. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226994.htm

35. TZD’s: Response detail as of 3/31/2011: • Note that providers may choose more than one selection per response. • Reviewed and have or will modify the treatment 4 • Attempted to modify therapy unsuccessfully 4 • Information clinically useful: plan to monitor 2 • Previously saw this pt, but no longer in my care 3 • Very useful to my practice 2 • Somewhat useful to my practice 2 • Will change dose 1

36. TZD’s: Comments of Interest* • Profile ID: 0001642778: I am already complying with the above and am no longer prescribing Avandia®. • Note that prescriber also wrote in next to number 8 that medication was reordered on January 26, 2011 * Profile is in member packet for your review

37. PPI’s: Long Term Use • There are multiple risks associated with long term Proton Pump Inhibitor (PPI) use. • Patients were selected for evaluation if they had at least 8 claims for a PPI over the six month period. • Profiles are under development. • See packet for copy of the letter and Educational Information Handout*

38. PPI’s: Long Term Use • Risk of Fracture:  On May 25, 2010, the FDA revised the prescription label for the proton pump inhibitor (PPI) class of drugs to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine with the use of these medications. There is an associated 25% increase in overall fractures and a 47% increase in spinal fractures in postmenopausal women. 

39. PPI’s: Long Term Use • Hypomagnesemia: The FDA has also issued a statement warning that PPIs taken for prolonged periods of time (in most cases, longer than one year) may also cause low serum magnesium levels.  Low serum magnesium levels can lead to muscle spasm, irregular heartbeat, and convulsions.  • Enteric infections: Reduction in acidity may promote bacterial colonization of the gastrointestinal tract which may result in clostridium difficile colitis or bacterial gastroenteritis.

40. PPI’s: Long Term Use • Community-acquired pneumonia: Reduction in acidity may allow ingested pathogens to colonize the stomach with subsequent translocation which increases the incidence of community-acquired pneumonias.

41. PPI’s: The review criteria was for 8 or more fills within a six month period. Considered doses above the FDA approved dose for GERD as high as listed in table. *Zegerid® not payable by Idaho Medicaid

42. PPI’s Criteria Paragraph • During a retrospective drug utilization review, it was noted that your patient, «MemberName», has received  8 or more fills for a PPI over the 6 month review period.  The FDA has recently revised the prescription label for the proton pump inhibitor (PPI) class of drugs to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine and may also cause low serum magnesium levels. The FDA recommends that when healthcare professionals prescribe PPI's, they should utilize the lowest dose and shortest duration of therapy to adequately treat the patient's condition.

43. PPI’s: Findings Upon Review:

44. PPI’s: Findings Upon Review: • Four participants < 50 years of age were previously denied twice daily therapy • three are now receiving two PPIs • one is now receiving two PPIs and an H2 antagonist • Three participants over 49 years of age are receiving one PPI at GERD dosing

45. Investigate issues of low dose atypical antipsychotics being used for sleepSpecific Aim 1: Among Medicaid beneficiaries with a mental illness, compare utilization trends of newer sedative hypnotics, alone and in combination with other psychotropics, across three state Medicaid programs from 2003-2008.Specific Aim 2: Examine the effects of prescription access policies on the utilization of newer sedative hypnotics, pre-to-post policy implementation in each state, and potential substitutions to other psychotropic drugs such as low dose atypical antipsychotics.Specific Aim 3: Compare the impact of implementing prescription access restriction policies on overall prescription drug expenditures and service utilization expenditures among Medicaid beneficiaries with a mental illness diagnosis, pre- and post-policy implementation.Specific Aim 4: Compare changes in use of sleep aids (atypical antipsychotics and/or newer sedative hypnotics) attributable to changes in drug policy between people with and without documented mental illness.NIMH Study Specific Aims • Specific Aim 1: Among Medicaid beneficiaries with a mental illness, compare utilization trends of newer sedative hypnotics, alone and in combination with other psychotropics, across three state Medicaid programs from 2003-2008.Specific Aim 2: Examine the effects of prescription access policies on the utilization of newer sedative hypnotics, pre-to-post policy implementation in each state, and potential substitutions to other psychotropic drugs such as low dose atypical antipsychotics.Specific Aim 3: Compare the impact of implementing prescription access restriction policies on overall prescription drug expenditures and service utilization expenditures among Medicaid beneficiaries with a mental illness diagnosis, pre- and post-policy implementation.Specific Aim 4: Compare changes in use of sleep aids (atypical antipsychotics and/or newer sedative hypnotics) attributable to changes in drug policy between people with and without documented mental illness.

46. Proposed Studies for Next Quarter: • Analysis of Auto Refill Practice* • Atypical Antipsychotics: Impact of P&T Recommendations • Colchicine Usage • Place in Therapy for Treatment of Gout • High Dose Utilization Through Multiple Dosage Strengths • Oxycodone • Atypical Antipsychotics • Injectable Antipsychotics All information based on Idaho Medicaid Pharmacy Data 1stQuarter 2011 (1/1/11-3/31/11) unless otherwise indicated.

47. 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

48. Atypical AntipsychoticsP&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.

49. Atypical AntipsychoticsP&T Recommendations

50. Atypical AntipsychoticsP&T Recommendations (continued) • Adherence Rates