Idaho Medicaid Drug Utilization Review Program

1. Idaho Medicaid Drug Utilization Review Program 19 January 2012

2. Follow-up to Previous Reviews • Analysis of Auto Refill Practice • Hepatitis C • Transdermal Testosterone Utilization • Oral Terbutaline Utilization • Thiazolidinediones (TZD’s)

3. Auto Refill Practices • Fax blast of survey went out to 318 pharmacies on July 8, 2011. • As of 1/16/2012 a total of 78 surveys have been returned (25% response rate)

4. 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

5. Auto Refill Practices • Several States currently do not allow Auto Refill of prescription medications for their Medicaid participants. • Several points regarding Auto Refill were discussed. Dr. Brown suggested that a two pronged approach be considered: : #1 Rule based change is done for Idaho Medicaid and/or #2 Statutory based change possibility that auto refill not be allowed for any Idaho citizen regardless of payer.

6. 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.

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

8. 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)

9. 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.

10. 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)

11. 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.

12. 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. • Prior authorization for Incivek and Victrelis with therapeutic criteria is NOT recommended at this time due to recommendation from P&T Committee. DUR project will be done in approximately 6 months to evaluate for appropriateness and whether or not patients completed the course of triple therapy.

13. 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)

14. Transdermal Testosterone DUR • Product Selection • Preferred agents • Androgel n=91 • Androderm Patches n=31 • Non-preferred agents • Testim Gel n=1 • Fortesta Gel n=0 • Axiron Underarm Solution n=0

15. Transdermal Testosterone DUR • Patient Diagnoses

16. Transdermal Testosterone DUR • Potential Cost Savings • $133,447 paid in claims for the study period • If only paid claims for patients with diagnosis of hypogonadism (n=50), cost savings would be $79,200. • Reference • Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology & Metabolism, June 2010, Vol 95(6):2536-2559. Evidence based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of the evidence.

17. Transdermal Testosterone DUR • Diagnosis of androgen deficiency in men • Consistent symptoms and signs • Unequivocally low serum testosterone levels: Defined as a morning level below the normal range as defined by the testing laboratory (the lower limit of normal testosterone is approximately 280-300ng/dl but may vary slightly between laboratories). Serum testosterone levels exhibit a circadian variation with peak values in the morning. Confirm low testosterone concentration in men with an initial testosterone level in the mildly hypogonadal range because 30% of such men may have a normal testostosterone level on repeat measurement.

18. Transdermal Testosterone DUR • More specific symptoms and signs of androgen deficiency in men • As defined by the Endocrine Society • Incomplete or delayed sexual development, eunuchoidism • Reduced sexual desire (libido) and activity • Decreased spontaneous erections • Breast discomfort, gynecomastia • Loss of body (axillary and pubic) hair, reduced shaving • Very small (especially <5ml) or shrinking testes • Inability to father children, low or zero sperm count • Height loss, low trauma fracture, low bone mineral density • Hot flushes, sweats • Idaho Medicaid does not cover for the s/s underlined

19. Transdermal Testosterone DUR • Less specific symptoms and signs of androgen deficiency in men • As defined by the Endocrine Society • Decreased energy, motivation, initiative, and self-confidence • Feeling sad or blue, depressed mood, dysthymia • Poor concentration and memory • Sleep disturbance, increased sleepiness • Mild anemia (normochromic, normocytic, in the female range) • Reduced muscle bulk and strength • Increased body fat, body mass index • Diminished physical or work performance • As these symptoms/signs are quite non-specific, need to have these in conjunction with at least one symptom/sign from previous slide.

20. Transdermal Testosterone DUR • Follow-Up Laboratory Determination in 3-6 months • Achieve testosterone level during treatment in the mid-normal range; test 3-6 months after therapy has started • Then Annual Monitoring • Assess whether symptoms have responded to treatment • Assess whether patient is suffering any adverse effects • Assess adherence to therapy

21. Transdermal Testosterone DUR • Duration of Therapy • For patients with a start and stop date within this study period (defined as first fill after July 1, 2010 and last fill prior to May 26, 2011) N=65

22. Transdermal Testosterone DUR • Number of Prescriptions

23. Transdermal Testosterone DUR • Duration with respect to diagnosis

24. Transdermal Testosterone DUR • Recommendations • Initiate therapeutic criteria for transdermal testosterone • Diagnosis of hypogonadism • At least one non-sexual dysfunction symptom • Serum testosterone level below the lower limit of normal • Contact prescribers of current patients receiving transdermal testosterone (prescription filled within the last 60 days) informing them of the therapeutic criteria and requesting documentation of the points listed above. For study period, would be 35 Androgel patients and 18 Androderm patients but will run more recent list.

25. Transdermal Testosterone DUR • Recommendations, continued • Initial approval would be for three months • Then follow-up serum testosterone level would be required (should be in mid-normal range). • Subsequent approvals would be for one year. Requirements for annual renewal would be: • Serum testosterone level while on therapy • Documentation that symptoms have responded to treatment • Documentation that patient is not experiencing adverse effects • Assessment of adherence to therapy

26. Transdermal Testosterone DUR • Proposed testosterone DUR letter paragraph: • Your patient, NAME, has a paid pharmacy claim for a topical testosterone agent within the last 60 days. Idaho Medicaid’s Pharmacy and Therapeutics Committee recommended that prior authorization with therapeutic criteria be added to the topical androgenic drug class. Idaho Medicaid’s Drug Utilization Review (DUR) Board reviewed usage from June 2010 to June 2011 and only 41% of the patients who received a topical testosterone agent had a documented diagnosis of hypogonadism in their electronic profile. Effective DATE, prior authorization with therapeutic criteria will be required for this drug class. Patients will be approved for therapy if they have (1) diagnosis of hypogonadism, (2) documented serum testosterone level that is below the lower limit of the normal range, and (3) clinical signs/symptoms of hypogonadism. If you wish for your patient to continue topical testosterone therapy, please complete the attached prior authorization form and submit to Idaho Medicaid.

27. Oral Terbutaline Utilization • FDA Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor • On February 17, 2011, the Food and Drug Administration (FDA) released a Safety Announcement addressing the use of terbutaline for preterm labor and the potential adverse effects it can have on the mother. • A review of Idaho Medicaid Recipients showed that between 5/1/2011 and 7/31/2011 there was a total of 28 female recipients between the ages of 10-55 who received prescriptions for terbutaline.

28. Oral Terbutaline Utilization • Review of the data included female patients between the ages of 10-55, n=28. • Female patients < 10 years or > 55 years: 1 - 62 year old • No male patients • 23/28 patients had a pregnancy diagnosis in the electronic profile. • Average age 27 years (range 19-37) • 1 fill – 22 • 2 fills – 5 • 3 fills – 1 • Average fill was for 35 tablets (range 3-90)

29. Oral Terbutaline Utilization

30. Oral Terbutaline Utilization • Based off this manual review of profiles by the State of Idaho Pharmacist, profiles were run for the time period of July 1, 2011 through September 30, 2011 and 24 patients were identified. • Letters will be generated and sent out to those prescribers who have prescribed terbutaline along with the FDA Safety Announcement and specific detailed question form. • Currently there is no Therapeutic Criteria for oral terbutaline, only pays within the age/quantity limits.

31. 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

32. Thiazolidinediones (TZD’s) • Patients were selected for evaluation if there was a paid claim for Avandia®, Avandamet®, or Avandaryl® 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 1/16/2012, 16 responses have been received (25% response rate.)

33. Thiazolidinediones (TZD’s) • Risk Evaluation and Mitigation Strategy (REMS) • Rosiglitazone REMS Program • Approved 05/2011 - Updated 11/2011 • 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

34. 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.

35. Thiazolidinediones (TZD’s) • Risk Evaluation and Mitigation Strategy (REMS) • As of November 18, 2011 GSK withdrew all rosiglitazone products from the current supply chain • 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

36. Thiazolidinediones (TZD’s)Number of claims

37. Current Interventions/Outcomes Studies • Citalopram High Dose • Oral Terbutaline Intervention • P&T Committee Narcotic Analgesic Studies • Transdermal Testosterone Intervention

38. Citalopram High Dose DUR • FDA Drug Safety Communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide) • On August 24, 2011, the Food and Drug Administration (FDA) released a Safety Announcement addressing the high dose of citalopram and potential adverse effects it can have on the heart. The maximum daily dose is now recommended to be 40 mg per day when it was previously 60 mg per day. • A review of Idaho Medicaid Recipients showed that during the previous 3 months 234 recipients had received doses greater than 40 mg per day.

39. Citalopram High Dose DUR • Letters were sent out about 235 patients on 10/6/2011 to 186 prescribers with a list of their patients along with the FDA Safety Announcement and Survey Response Form. (see Letter and Announcement in Packet) • As of 1/03/2012, 59 responses have been received (32% response rate)

40. Citalopram High Dose DUR: Response Detail as of 1/3/2012 • Note that providers may choose more than one selection per response. • Will use this information for care of future patients 28 • Reviewed info and have modified or plan to modify treatment 27 • Found Info clinically useful and plan to monitor patients 21 • Reviewed info and do not believe adjustment is necessary 19 • Very useful to my practice 18 • Will change dose 18 • Extremely useful to my practice 14 • Somewhat useful to my practice 10 • Not useful to my practice 6

41. Citalopram High Dose DUR: Response Detail as of 1/3/2012 • Note that providers may choose more than one selection per response. • Previously saw this patient, but no longer in my care 5 • Attempted to modify the therapy, but the patient response was not favorable 5 • Will discontinue medication 3 • Patient is under my care, but I am not prescriber for this med 2 • I am not the provider for this patient 1

42. Citalopram High Dose DUR:Response Detail as of 1/3/2012 • “Already aware. Refused to change as med is working. Acknowledges risks.” • “Pt has not been seen at our clinic since 12-13-2010. Currently in jail” • “Pt. weighs approx 375 lb. I believe he requires a higher dose than normal wt individual” • “I believe further investigation was warranted before this change was enacted” • “He is on 20-30mg, Not at the accused 40mg. How did you get the misinformation. Other Doctor is handling all meds.” • Profile reviewed and patient was on 10mg/5ml and filled 120ml’s 9/21/2011 & 12/29/2011 • “Pt now taking only 40mg” • Profile reviewed and patient is currently taking venlafaxine ER • “Will change dose if pt follows up. This pt has failed follow-up and is out of refills”

43. Citalopram High Dose DUR:Response Detail as of 1/3/2012 • “Each pt. individually evaluated and backing clinically from higher than recommended dose. Have or will discuss ECG monitoring. Improved depression response with more than 60mg per day” • “As a psychiatrist, I am aware of the indications for psychotropic's and I do my best to minimize the use of antipsychotics. Pt. did report improvement on 60mg QD. Pt due for follow-up and will reduce dose back to 40mg at that time. I question why this info was not available much earlier as this Rx has been on the market a long time-i.e., re the potential cardiac S.E.” • “Pt OK off celexa” • Profile reviewed and patient is currently taking paroxetine • “We have attempted reducing with poor response. Have actually added bupropion. Pt had wanted further increases but stabilized with addition of bupropion.” • “Was aware of the new dose recommendations but appreciate help identifying pts who are currently getting doses higher than 40mg.”

44. Citalopram High Dose DUR:Response Detail as of 1/3/2012 • “She is stable. In early Sept. incr. anxiety.” • “Pt needs to be informed of meds.” • “Pt is not in our system as an existing pt or a treated pt. Thanks.” • “This pt has moved to Texas and I no longer see him.” • “Dose already decreased to 40mg” • Profile reviewed and dose decreased from 60mg to 40mg on 11/15/2011 • “He is on 8mg per day” • “Will have EKG” • “Pt is currently stable on dose and no side effects noted.” • “Pt takes 10mg per 5 ml x 15 ml day. This is 30mg per day. No change planned.” • “The dose is 20mg. I am already aware of FDA warning, but thanks!” • “Consult with parent”

45. Citalopram High Dose DUR:Response Detail as of 1/3/2012 • “This Pt has the following dose – citalopram 10mg/5ml. 10ml qd for 20 mg per day” • “Will decrease dose to 40mg.” • “Pt is not on citalopram at this time” • Profile reviewed and patient filled #45 - 40mg on 9/17/2011, 10/17/2011, 11/14/2011, and 12/15/2011 • “Risks and benefits were discussed with pt regarding high dose. Pt felt that stability was best if med had been. Will check ECG.” • “Pt is on 10mg citalopram not 40mg. Other Pt is on 15mg not 40mg” • Profiles reviewed and patients were on 10mg/5ml. • “Will have EKG” • “I did not prescribe this med. No longer my patient.” • “She is already on another med. Citalopram was dc-d.” • “May change to another med” • “Pt is stable and monitored q 2 wk. Will check EKG”

46. Citalopram High Dose DUR:Response Detail as of 1/3/2012 • “Pt stopped medication on his own – months ago” • “I would recommend a reduction” • “Condition stable. Increase symptoms on lower dose.” • “Condition is improved. Stable on higher dose.” • “It does seem that the pt has already had her dose reduced to 40mg per day” • “According to my records, pt is on 10mg per day” • “Have already adjusted dose to 40mg” • “She was on this dose upon transfer to me from hospital” • “Pt is responding well to medication. Adjusting dose would be detrimental. I will obtain an EKG.” • “Current dose effective but have not seen client recently to change dose. Will need to speak to guardian.” • “Will change dose to 40mg” • “Will reconsider dosing”

47. Citalopram High Dose DUR • Recommendations • Decrease the maximum daily dose to the FDA recommended 40mg. • Require a quantity override Prior Authorization for any claims with a dose greater than 40mg per day. • Grandfather recipients currently on greater than 40mg per day???

48. Oral Terbutaline Intervention • Letters were sent out on 12/7/2011 to prescribers of the 24 patients identified along with the FDA Safety Announcement and Survey Response Form. (see Letter, Announcement, and Prescriber Response Form in Packet) • As of 1/03/2012, 3 responses have been received (13% response rate)

49. Oral Terbutaline Intervention:Response Detail as of 1/3/2012 • Note that providers may choose more than one selection per response. • Any pts who received oral terbutaline for preterm labor experienced serious side effects – NO 3 • Additional Comments 1 • “premature Zolcor suppression Magnesium Sulfate. Should the use be suppressed when other agents have been unsuccessful.” • Oral terbutaline for any pt for preterm labor – YES 1 • “If nifedipine is not tolerated, terbutaline works well. It helps manage discomfort and contraction frequency. It decreases the number of trips patients make to labor and delivery for contractions. I don’t use terbutaline often, but it still has a role in some patients.” • Oral terbutaline for any pt for preterm labor – NO 1 • Diagnosis for which terbutaline was prescribed 1 • “Preterm contractions, RAD”

50. Oral Terbutaline Intervention: • Recommendations from the Board ???