Drug Therapy Guidelines

Transcription

1 Drug Therapy Guidelines Applicable Medical Benefit Effective: 8/15/18 Pharmacy- Frmulary 1 x Next Review: 6/19 Pharmacy- Frmulary 2 x Date f Origin: 10/99 Grwth Stimulating Drugs: Nrditrpin Flexpr, Gentrpin, Humatrpe, Omnitrpe, Nutrpin, Saizen, Serstim, Zmactn TM, Zrbtive (smatrpin, recmbinant grwth hrmne) Pharmacy- Frmulary 3/Exclusive x Review Dates: 10/99, 11/28/00, 3/9/01, 4/26/01, 12/16/03, Pharmacy- Frmulary 4/AON x 11/16/04, 9/14/05, 8/29/06, 11/5/07, 12/15/08, 12/09, 3/10, 1/11, 12/11, 12/12, 12/13, 12/14, 6/15, 6/16, 6/17, 6/18 I. Medicatin Descriptin Endgenus grwth hrmne (GH) is respnsible fr stimulating nrmal skeletal, cnnective tissue, muscle, and rgan grwth in children and adlescents. It als plays an imprtant rle in adult metablism. Recmbinant prducts mimic all f these actins. Smatrpin (recmbinant grwth hrmne) is typically administered subcutaneusly r intramuscularly nce daily. While all grwth hrmne prducts are variatins f smatrpin, sme prducts are apprved by the U.S. Fd and Drug Administratin fr different pediatric and adult indicatins. Grwth Hrmne Prducts Adult GHD* HIV Wasting CRD** ISS+ Nnan Syndrme Pediatric GHD* Indicatin Prader- Willi Syndrme SGA++ SHOX+++ Turner Syndrme Gentrpin Humatrpe Nrditrpin Flexpr Nutrpin, Nutrpin AQ Omnitrpe Saizen Serstim Zmactn TM Zrbtive *GHD =grwth hrmne deficiency/insufficiency **CRD = grwth failure due t chrnic renal disease +ISS = idipathic shrt stature ++SGA = small fr gestatinal age +++SHOX=treatment f shrt stature / grwth failure in children with hmebx-cntaining gene deficiency Shrt Bwel Syndrme II. Psitin Statement Cverage is determined thrugh a prir authrizatin prcess with supprting clinical dcumentatin fr every request. Page 1 f 9

2 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 III. Plicy Frmulary 1: See Sectins A, B Frmulary 2: See Sectins A, B Frmulary 3/Exclusive: See Sectins A, B Frmulary 4/AON: See Sectins A, B A. Prir authrizatin criteria: Prescriber Requirements: Pediatric members are under the care f a pediatric endcrinlgist r a pediatric nephrlgist with expertise in grwth hrmne. Adult therapy must be rdered r recmmended by an apprpriate specialist fr diagnsis. Cverage is prvided fr the fllwing diagnses: Pediatric grwth hrmne deficiency: Epiphyses must be cnfirmed as pen in members 10 years f age AND GH deficiency established by: Grwth hrmne deficiency cnfirmed by any 2 prvcative test results belw 10 ng/ml [Nte: tests must be perfrmed with 2 different agents e.g. L-Dpa, insulin-induced hypglycemia, arginine, glucagn, clnidine] OR One prvcative stimulatin test less than 15 ng/ml, cmbined with a lw insulin-like grwth factr-1 (IGF-1) level and lw IGFBP-3 (insulin-like grwth factr binding prtein-3) fr age, gender, and pubertal status [Nte: Lw is defined as being in the lwer half f the nrmal reference range, r belw the nrmal reference range. Reference range will vary with the lab assay used therefre results shuld be interpreted against the standards prvided by the lab perfrming the test] AND Grwth failure established by: Member s height must be belw the third percentile fr their age and gender related height AND / OR Grwth velcity subnrmal 2 standard deviatins (SD) frm the agerelated mean measured ver 1 year AND Delayed skeletal maturatin 2 SD belw the age/gender related mean Pediatric grwth failure due t chrnic kidney disease: Member has nt received a renal transplant AND Member s height must be belw the third percentile fr their age and gender related height as demnstrated n updated grwth chart Grwth failure in children brn small fr gestatinal age (SGA): Member is brn SGA, defined as grwth charts shwing birth weight, birth length, r bth that are mre than 2 standard deviatins belw mean nrmal values fllwing adjustment fr age and gender AND Failed t manifest catch-up grwth by age 2 Turner s syndrme in girls: Page 2 f 9

3 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 Karytype analysis cnfirms diagnsis (45, XO gentype) AND Member height falls belw the fifth percentile fr age (which usually ccurs between tw and five years f age) demnstrated n updated grwth chart with baseline height and weight Prader-Willi syndrme: Assessment fr any underlying airway bstructin including sleep study is prvided AND Diagnsis cnfirmed by apprpriate genetic testing (lss f gene functin assciated with chrmsme 15 such as translcatin r maternal uniparental dismy) AND Cntraindicated fr use in members with severe besity (e.g., weight >225 percent f ideal bdy weight), respiratry cmprmise, r severe sleep apnea AND Baseline height and weight is prvided Nnan Syndrme: Chart dcumentatin is prvided cnfirming diagnsis AND Updated grwth chart is prvided Shrt stature r grwth failure in children with shrt stature hmebx (SHOX) deficiency: Diagnsis demnstrated by chrmsme analysis AND Updated grwth chart is prvided Adult grwth hrmne deficiency: Adult-nset grwth hrmne deficiency islated grwth hrmne r multiple hrmne deficiencies (hyppituitarism), as a result f pituitary disease, hypthalamic disease, surgery, radiatin therapy, r trauma with ne f the fllwing: Serum IGF-1 cncentratin is lwer than the age-specific lwer limit f nrmal in a member wh has rganic pituitary disease OR If IGF-1 is nt subnrmal, a subnrmal GH respnse t insulin-induced hypglycemia (<5.1 ng/ml) r arginine-ghrh (<4.1ng/ml) is necessary t cnfirm diagnsis Childhd nset grwth hrmne deficiency as a result f cngenital, genetic, acquired, r idipathic causes: A perid f at least ne mnth shuld pass befre re-evaluating GH status after therapy has been discntinued at final height AND ne f the fllwing: Retesting has been perfrmed using Insulin tlerance test (ITT) as a first-line unless cntraindicated (examples: members at high risk fr crnary artery disease r with a histry f seizures) OR Alternative testing when ITT cntraindicated: grwth hrmne releasing hrmne (GHRH)+arginine (ARG) test glucagn test ARG test alne OR Retesting is waived due t: Page 3 f 9

4 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 knwn mutatins, embrypathic/cngenital defects, irreversible hypthalamic-pituitary structural lesins AND evidence f panhyppituitarism (at least 3 pituitary hrmne deficiencies) AND IGF-I levels belw the age- and sex-apprpriate reference range fr GH therapy Cverage f Zrbtive (r Nrditrpin Flexpr, if requested) is prvided fr the treatment f shrt bwel syndrme when: Diagnsis is dcumented as a result f resected r damaged bwel with chrnic diarrhea, weight lss, electrlyte imbalances, malnutritin, dehydratin, and malabsrptin f fats, vitamins and minerals AND There is dependence n specialized nutritinal supprt needs including dietary adjustments such as a high carbhydrate, lw fat diet, enteral feedings, parenteral nutritin, fluid, and micrnutrient supplements demnstrated thrugh nutritinist cnsultatin, dietary interventins, pertinent labs Cverage f Serstim is prvided fr the treatment f HIV members with wasting r cachexia when: Member is 18 years f age AND Cmparative weights and heights are dcumented AND Wasting syndrme is nt attributable t ther causes such as; depressin, MAC, chrnic infectius diarrhea, r malignancy (Kapsi s sarcma limited t the skin r mucus membranes is cvered) AND Cnfirmatin f wasting syndrme has been dcumented (e.g., unintentinal weight lss f at least 10% f bdy weight) AND Optimal antiretrviral therapy has been attempted AND Failure f nn-invasive frms f nutritinal therapy (such as appetite stimulants like megestrl acetate and drnabinl). B. Step therapy: A step edit is in place whereby nn-preferred medicatins (Gentrpin, Humatrpe, Omnitrpe, Nutrpin, Saizen, Zmactn) will nly be cvered fr members wh have failed a trial with the plan-preferred medicatin (Nrditrpin Flexpr): When requesting cverage f a brand medicatin fr which an A/B rated generic is available, there is sufficient evidence that the use f the A/B rated generic equivalent has resulted in inadequate results AND Member must have attempted and failed an adequate (3 mnth) trial with the plan-preferred medicatin smatrpin (Nrditrpin Flexpr) befre any ther grwth hrmne medicatin will be cvered OR when at least ONE f the fllwing criteria have been met: The plan-preferred medicatins are cntraindicated r will likely cause an adverse reactin by r physical r mental harm t the member. The plan-preferred medicatins are expected t be ineffective based n the knwn clinical histry and cnditins f the member and the member s prescriptin drug regimen. The member has tried the plan-preferred medicatins r anther prescriptin drug in the same pharmaclgic class r with the same mechanism f actin and such prescriptin drug was discntinued due t lack f efficacy r effectiveness, diminished effect, r an adverse event. The member is stable n the medicatin selected by their healthcare prfessinal fr the Page 4 f 9

5 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 medical cnditin under cnsideratin (where stable is defined as receiving the medicatin fr an adequate perid f time, have achieved ptimal respnse, and cntinued favrable utcmes are expected UNLESS the medicatin was initially selected slely due t the availability f a drug sample r a cupn card and the member des nt therwise meet the definitin f stable ). The plan-preferred medicatin is nt in the best interest f the member because it will likely cause a significant barrier t the member s adherence r t cmpliance with the member s plan f care, will likely wrsen a cmrbid cnditin f the member, r will likely decrease the member s ability t achieve r maintain reasnable functinal ability in perfrming daily activities. Exceptins: Nrditrpin Flexpr trial will NOT be required when: Zrbtive is used fr treatment f shrt bwel syndrme OR Serstim is used in HIV related cachexia r wasting. IV. Quantity Limits Cverage is available as fllws: Adults Gentrpin and Omnitrpe: 0.08 mg/kg/week Humatrpe: mg/kg/day Nrditrpin Flexpr: mg/kg/day Nutrpin and Nutrpin AQ: mg/kg/day in members yunger than 35 years f age; mg/kg/day in members 35 years f age and lder Saizen: 0.01 mg/kg/day Serstim: 6 mg/day (weight dependent) Zrbtive: 8 mg/day Children- Dsing adjustments in children are dependent upn maintaining IGF-1 levels within a targeted range; therefre, maximum units are individualized. V. Cverage Duratin Pediatric human grwth hrmne deficiency, grwth failure in children SGA, grwth failure due t Turner s syndrme, Nnan Syndrme, SHOX, chrnic renal failure, r Prader-Willi Syndrme: Nrditrpin Flexpr: cverage prvided fr 12 mnths and may be renewed All ther grwth hrmne prducts: cverage prvided fr 3 mnths with fllw-up authrizatins f up t 12 mnths depending n cmparative respnse (see Step-Therapy requirements) Adult grwth hrmne deficiency Nrditrpin Flexpr: cverage prvided fr 12 mnths and may be renewed All ther grwth hrmne prducts: cverage prvided fr 3 mnths with fllw-up authrizatins f up t 12 mnths depending n cmparative respnse (see Step-Therapy requirements) Shrt bwel syndrme: Zrbtive: 1 mnth and may be renewed Nrditrpin Flexpr: cverage is prvided fr 6 mnths and may be renewed HIV-related wasting r cachexia: 3 mnths and may be renewed Page 5 f 9

6 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 VI. Cverage Renewal Criteria Cverage may be renewed accrding t the fllwing criteria in the absence f unacceptable txicity frm the drug: Pediatric human grwth hrmne deficiency, grwth failure in children SGA, grwth failure due t Turner s syndrme, Nnan Syndrme, SHOX, r chrnic renal failure: pen epiphyses dcumented (bne age f 16 years fr bys, 14 years fr girls) AND grwth respnse f at least 4.5 cm/yr (prepubertal grwth rate) r at least 2.5 cm/yr (pstpubertal grwth rate) dcumented with updated grwth chart and recent height and weight with date measured Prader-Willi Syndrme: Updated grwth chart and recent height and weight with date measured AND Dcumented increase in lean bdy mass (r decrease in fat) OR Maintenance f benefit in males up t 16 years f age and in females up t 14 years f age Adult grwth hrmne deficiency: Clinical benefit dcumented (e.g., increase in ttal lean bdy mass, increase in IGF-1 and IGFBP- 3 levels, r increase in exercise capacity) AND Benefit seen frm cmparative weight t baseline with height Shrt bwel syndrme: Prgress ntes shwing benefit AND Applicable labs/testing shwing benefit AND Renewable in situatins where the member is deriving clinical benefit (e.g., the member is experiencing a decrease in intravenus nutritin requirements) HIV-related wasting r cachexia: Renewable in the presence f weight stabilizatin r increase dcumented with height and cmparable weights VII. Billing/Cding Infrmatin Pertinent diagnses: B20 C75.1, C75.2 Human immundeficiency virus (HIV) disease Malignant neplasm f pituitary gland and cranipharyngeal duct C79.31 Secndary malignant neplasm f brain and spinal crd D35.2, D35.3 Benign neplasm f pituitary gland and cranipharyngeal duct D44.3, D44.4 Neplasm f uncertain behavir f pituitary gland and cranipharyngeal duct E23.0 Panhyppituitarism E23.0 Pituitary dwarfism E23.6 Unspecified anterir pituitary disrders E22.2 Other disrders f neurhypphysis E23.1, E89.3 Iatrgenic pituitary disrders Page 6 f 9

7 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 E23.6 Other disrders f the pituitary and ther syndrmes f diencephalhypphyseal rigin E23.3, E23.7 Unspecified endcrine disrder K91.2 Other and unspecified pstsurgical nnabsrptin N18.2 Chrnic kidney disease, stage ii (mild) N18.3 Chrnic kidney disease, stage iii (mderate) N18.4 Chrnic kidney disease, stage iv (severe) N18.5 Chrnic kidney disease, stage v N18.6 End stage renal disease N18.9 Chrnic kidney disease, unspecified Q96.9 Gnadal dysgenesis (i.e., Turner's syndrme) Q87.1 Prader-Willi syndrme Q87.1 Russell-Silver syndrme R62.50 Lack f physilgical develpment R64 Cachexia Z92.3 Persnal histry f irradiatin presenting hazards t health VIII. Summary f Plicy Changes 3/1/11: Increlex plicy mved t separate guideline Remval f Idipathic Shrt Stature frm cvered indicatins Step-Therapy Mdified t ne plan-preferred prduct (Nrditrpin ) 6/15/12: Additinal indicatins added t Omnitrpe Pancreatitis and benzyl alchl warnings added Required dcumentatin added t criteria 3/15/13: clarified which plans have step therapy requirements 7/1/13: Cmmercial Rx and Medicaid/Family Health Plus criteria differentiated 3/15/14: n plicy changes 3/15/15: n plicy changes 7/1/15: frmulary distinctins made Zmactn added t plicy 9/15/15: n plicy changes 2/3/16: clarificatin made that Nrditrpin wuld be cnsidered fr cverage in the treatment f shrt bwel syndrme 7/19/16: n plicy changes 5/1/17: step therapy criteria added 6/21/17: n plicy changes 8/15/18: specified prvcatin tests must be perfrmed using 2 different agents Page 7 f 9

8 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/2018 defined lw values fr IGF added Nrditrpin Flexpr frmulatins IX. References 1. UpTDate Online, retrieved April Clinical Pharmaclgy: Elsevier/Gld Standard. Smatrpin mngraph. Accessed 3/ Facts and Cmparisns Online, retrieved January Micrmedex - Smatrpin Drugdex Evaluatin. Thmpsn Reuters. Accessed 4/ Prduct Infrmatin: Gentrpin. Revised 12/ Prduct Infrmatin: Humatrpe. Revised 12/ Prduct Infrmatin: Nrditrpin Flexpr. Revised 2/ Prduct Infrmatin: Omnitrpe. Revised 12/ Prduct Infrmatin: Nutrpin. Revised 12/ Prduct Infrmatin: Saizen. Revised 5/ Prduct Infrmatin: Serstim. Revised 5/ Prduct Infrmatin: Zmactn TM. Revised 1/ Prduct Infrmatin: Zrbtive. Revised 5/ Vimalachandra D, Hdsn EM, Willis NS, Craig JC, Cwell C, Knight JF. Grwth hrmne fr children with chrnic kidney disease. Cchrane Database Syst Rev. 2006;3:CD Seikaly MG, Salhab N, Warady BA, Stablein D. Use f rhgh in children with chrnic kidney disease: lessns frm NAPRTCS. Pediatr Nephrl. 2007;22(8): Mahan JD, Warady BA, Cnsensus Cmmittee. Assessment and treatment f shrt stature in pediatric patients with chrnic kidney disease: a cnsensus statement. Pediatr Nephrl. 2006;21(7): Haffner D, Wühl E, Schaefer F, Nissel R, Tönshff B, Mehls O. Factrs predictive f the shrt- and lng-term efficacy f grwth hrmne treatment in prepubertal children with chrnic renal failure. The German Study Grup fr Grwth Hrmne Treatment in Chrnic Renal Failure. J Am Sc Nephrl. 1998;9(10): Mencarelli F, Kiepe D, Lezappa G, Stringini G, Cappa M, Emma F. Grwth hrmne treatment started in the first year f life in infants with chrnic renal failure. Pediatr Nephrl. 2009;24(5): Saenger P, Wikland KA, Cnway GS, Davenprt M, Gravhlt CH, Hintz R, Hvatta O, Hultcrantz M, Landin- Wilhelmsen K, Lin A, Lippe B, Pasquin AM, Ranke MB, Rsenfeld R, Silberbach M. Recmmendatins fr the diagnsis and management f Turner syndrme. J Clin Endcrinl Metab. 2001;86(7): Bndy CA, Turner Syndrme Study Grup. Care f girls and wmen with Turner syndrme: a guideline f the Turner Syndrme Study Grup. Clin Endcrinl Metab. 2007;92(1): Richmnd EJ, Rgl AD. Grwth hrmne deficiency in children. Pituitary. 2008;11(2): Grwth Hrmne Research Sciety. Cnsensus guidelines fr the diagnsis and treatment f grwth hrmne (GH) deficiency in childhd and adlescence: summary statement f the GH Research Sciety. GH Research Sciety. J Clin Endcrinl Metab. 2000;85(11): Biller BM, Samuels MH, Zagar A, Ck DM, Arafah BM, Bnert V, Stavru S, Kleinberg DL, Chipman JJ, Hartman ML. Sensitivity and specificity f six tests fr the diagnsis f adult GH deficiency. J Clin Endcrinl Metab. 2002;87(5): Page 8 f 9

9 Drug Therapy Guidelines Grwth Stimulating Drugs Last Review Date: 6/ Mlitch ME, Clemmns DR, Malzwski S, Merriam GR, Shalet SM, Vance ML, Endcrine Sciety's Clinical Guidelines Subcmmittee, Stephens PA. Evaluatin and treatment f adult grwth hrmne deficiency: an Endcrine Sciety Clinical Practice Guideline. J Clin Endcrinl Metab. 2006;91(5): Chen P, Rgl AD, Deal CL, Saenger P, Reiter EO, Rss JL, Chernausek SD, Savage MO, Wit JM. Cnsensus statement n the diagnsis and treatment f children with idipathic shrt stature: a summary f the Grwth Hrmne Research Sciety, the Lawsn Wilkins Pediatric Endcrine Sciety, and the Eurpean Sciety fr Paediatric Endcrinlgy Wrkshp. J Clin Endcrinl Metab. 2008;93(11): Claytn PE, Cianfarani S, Czernichw P, Jhannssn G, Rapaprt R, Rgl A. Management f the child brn small fr gestatinal age thrugh t adulthd: a cnsensus statement f the Internatinal Scieties f Pediatric Endcrinlgy and the Grwth Hrmne Research Sciety. J Clin Endcrinl Metab. 2007;92(3): Byrne TA, Wilmre DW, Iyer K, Dibaise J, Clancy K, Rbinsn MK, Chang P, Gertner JM, Lautz D. Grwth hrmne, glutamine, and an ptimal diet reduces parenteral nutritin in patients with shrt bwel syndrme: a prspective, randmized, placeb-cntrlled, duble-blind clinical trial. Ann Surg. 2005;242(5): Ck DM, Yuen KC, Biller BM, Kemp SF, Vance ML, American Assciatin f Clinical Endcrinlgists. American Assciatin f Clinical Endcrinlgists medical guidelines fr clinical practice fr grwth hrmne use in grwth hrmne-deficient adults and transitin patients update. Endcr Pract 2009 Sep-Oct;15 Suppl 2: Wilsn TA, Rse SR, Chen P, Rgl AD, Backeljauw P, Brwn R, Hardin DS, Kemp SF, Lawsn M, Radvick S, Rsenthal SM, Silverman L, Speiser P; Lawsn Wilkins Pediatric Endcrinlgy Sciety Drug and Therapeutics Cmmittee. Update f guidelines fr the use f grwth hrmne in children: the Lawsn Wilkins Pediatric Endcrinlgy Sciety Drug and Therapeutics Cmmittee. J Pediatr Oct;143(4): Drug Safety Cmmunicatin FDA-12/22/2010., htm The Plan fully expects that nly apprpriate and medically necessary services will be rendered. The Plan reserves the right t cnduct pre-payment and pst-payment reviews t assess the medical apprpriateness f the abve-referenced therapies. The preceding plicy applies nly t members fr whm the abve named pharmacy benefit medicatins are included n their cvered frmulary. Members with clsed frmulary benefits are subject t trying all apprpriate frmulary alternatives befre a cverage exceptin fr a nn-frmulary medicatin will be cnsidered. The preceding plicy is a guideline t allw fr cverage f the pertinent medicatin/prduct, and is nt meant t serve as a clinical practice guideline. Page 9 f 9