3Pharmacy and Therapeutics (P&T) Committee The role of the P&T Committee:Objectively appraises, evaluates, and selects drugs for formulary – value, place in therapy, and impact on budgetManages formulary in light of new drugs, indications, and warningsDevelop policies for educating and informing providers about new drugs and committee decisionsQuality improvementDevelop generic substitution and therapeutic interchange programsDevelop procedures for use and access to non-formulary drugsCommittee meets regularly throughout the yearMembers include physicians, pharmacists, administrators, and other health care professionals
5Overview of Diabetes Diabetes total U.S. prevalence in 2005 20.8 million people (7% of the population)Type 1: 5-10% of diagnosed casesType 2: 90-95% of diagnosed casesGestational: 20-50% of those will go on to have Type 2 in the next 5-10yrsMedications used by diabetics:57% Oral medications only16% Insulin only12% Insulin + Oral medications15% NoneDirect and indirect costs = $132 billion in 2002Risk factors for diabetes: genetic, sedentary lifestyle, overweight, pre-diabetes14.6 M are diagnosedType1: pancreas unable to produce insulinType 2: poor diet and exercise and other factors prevent the body from sensing insulin as well as it used toGestational: elevated glucose levels during pregnancy that may or may not resolvePre-diabetes – lots of inTalk about measures of glycemic control (A1C, blood glucose measures). When glycemic control is not achieved then you increase the risk of complications – kidney disease, peripheral neuropathy, retinopathy; hospitalizations/doctor visitsCDC National Diabetes Fact Sheet 2005
6Product InformationExubera® is a dry powder formulation of recombinant human regular insulin that is administered via oral inhalationIndication: Diabetes mellitus type 1 and 2Forms: Comes as 1mg or 3mg blister packsDose:Determined from preexisting premeal insulin or by weightAdminister 2-4 times/day 10min before meals
7Pharmacology Human insulin produced by recombinant DNA technology Insulin regulates glucose metabolism by stimulating uptake of glucose from the blood into skeletal muscle and fat and inhibiting hepatic glucose production.
8Pharmacokinetics Exubera® SubQ Regular Insulin After inhalation, insulin is rapidly absorbed across the pulmonary epitheliumMean time to peak serum concentration = 45minutesBioavailability:4.9-11% for nonsmokers12-19% for smokers
9Pharmacodynamics Onset of action = 10-20 min (similar to rapid-acting insulins)Duration of action =6 hrs (similar to regular)PD/PK differences existamong respiratorydiseases.More absorption in patients with COPD and smokersLess absorption in mild asthmaNo differences found between age, sex, pregnancyExubera® Package Insert.Clinical Pharmacology accessed Mar 2007
10Warnings and Interactions Contraindications:Hypersensitivity to Exubera®/any of its excipientsSmokers/ex-smokers<6monthsPoorly controlled lung diseaseAdverse Reactions:Hypoglycemia, chest pain, dry mouth, otitis media in pedsCough, dyspnea, pharnygitis, sputum, epistaxis, decrease in pulmonary function (FEV1)Common Drug Interactions:Reduce insulin’s effect: corticosteroids, diuretics, sympathomimetics, glucagon, estrogens/progesterone, protease inhibitors, atypical antipsychotics, thyroid hormonesIncrease insulin’s effect: oral antidiabetics, ACE-I, fibrates, fluoxetine, MAOI’sMask the symptoms of hypoglycemia: b-blockers, clonidineAffects absorption- leading to hypo- or hyperglycemia
11Place in Therapy Manufacturer Recommendations: Type 1: use in combo with longer-acting insulinType 2: use as monotherapy or with oral diabetic meds or longer-acting insulinEffective in patients poorly controlled on oral hypoglycemics or insulinMay be useful for patients who prefer inhaled over injected route for their rapid-acting insulinAmerican Diabetes Association Recommends:Inhaled insulin not included in treatment algorithmStatements on the ADA website question the long-term safety and cost-effectiveness of inhaled insulinOther published guidelines question the efficacy of inhaled insulin in lowering A1C<7%
13Submission of Clinical Trials The manufacturer should include:All pivotal clinical and economic studies – published and unpublishedSpreadsheet or table of these trialsMajor conclusions from Cochrane/Agency for Health Research and QualityAllows the P&T Committee to practice “evidence-based medicine”Evaluate quality, strength of clinical trialsWeigh out risks and benefits of drug, including no treatmentAccording to the Centre for Evidence-Based Medicine, "Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.
14Submission of Cost-Effectiveness Models Why do we need one?Projects the value of the product taking into account both efficacy and costHow the addition of the product will affect the health plan’s formularyDetermines the product’s place in therapy in the formularyCompares the product to “gold standards”What should one include?Take into account absolute and relative risk reductions, costs associated with administering this drug and its potential adverse effectsAssumptions and calculations should be reasonable and accurate
15Statement of Product Value Allows manufacturer to communicate value of productSummarize clinical and economic dataEstimate the per unit product costExample:“Inhaled insulin was demonstrated to have similar efficacy and side effects as injectable regular insulin, but patients prefer inhaled to injected. It may improve quality of life and reduce diabetic complications in those patients that are resistant or non-adherent to injectable insulin. Although it may cost more, it may generate savings if patients achieve better glycemic control due to better compliance to insulin therapy. ”
16Cost Comparison Table Regular Insulin (12,775 Units/year) Exubera® 1mg of Exubera® = 3 IU of Regular SC InsulinRelease unit needs to be replaced every 2 weeksCost comparison of a 70kg adult using 0.5 Units of regular insulin/kg/dayCosts are calculated over a year of useBased on AWPRegular Insulin(12,775 Units/year)Exubera®(4,380 mg/year)Syringes = $221.40Insulin vials = $787$10081 chamber= $1928 release units/year = $84Blister packs = $3042$3145++
17PA Criteria Patients must be: For Type 1 Diabetics: 18 years or older with a diagnosis of diabetes type 1 or 2Non-smokersNo hx of COPD, asthma, or other chronic respiratory diseaseDocumented A1C> 7% and baseline pulmonary function testFor Type 1 Diabetics:Must be used with a long-acting insulin (cannot use Exubera® as monotherapy)Patient has a need for short-acting insulin to achieve glycemic controlAND patient has difficulty with performing multiple injections (disability, blind)
18PA Criteria Continued For Type 2 Diabetics: First, must have tried and failed to achieve glycemic control w/ max doses of oral agents or are contraindicatedThen, must have tried to achieve glycemic control w/ a full injectable insulin regimen (long-acting + short-acting)AND patient has difficulty with performing multiple injections (disability, blind)Exubera® must be used in combination with a long-acting insulin and oral agents (unless contraindicated)