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Date Printed: December 17, 2017: 04:35 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-39

Original Effective Date: 06/15/15

Reviewed: 05/11/16

Revised: 06/15/16

Next Review: No Longer Scheduled for Routine Review (NLR)

Subject: Parathyroid Hormone (Natpara) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Parathyroid hormone (Natpara) was approved by the U.S. Food and Drug Administration (FDA) in January 2015 as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Because of the potential risk of osteosarcoma, use of parathyroid hormone is recommended only for patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone. Parathyroid hormone was not studied in patients with hypoparathyroidism caused by calcium-sensing receptor mutations or in patients with acute post-surgical hypoparathyroidism.

The efficacy of parathyroid hormone was evaluated in a 24-week, randomized, double-blind, placebo-controlled, multicenter trial. In this trial, patients with established hypoparathyroidism receiving calcium and active forms of vitamin D (vitamin D metabolite or analogs) were randomized (2:1) to parathyroid hormone (n=84) or placebo (n=40).

Before randomization, participants entered a 2-16 weeks run-in phase. In this phase calcium supplement and active vitamin D doses were adjusted to target an albumin-corrected serum calcium concentration between 8.0 and 9.0 mg/dL and 25-hydroxyvitamin D was replaced in patients with insufficient stores. At randomization, baseline serum calcium was 8.6 mg and participants were receiving a median (interquartile range) daily oral calcium dose of 2000 (1250, 3000) mg and a median daily oral active vitamin D dose equivalent to 0.75 mcg (0.5, 1) of calcitriol.

At randomization, active forms of vitamin D were reduced by 50% and patients were randomized to parathyroid hormone 50 mcg daily or placebo. Randomization was followed by a 12-week parathyroid hormone titration phase and a 12-week parathyroid hormone dose maintenance phase. During the titration phase parathyroid hormone was increased by 25 mcg increments every four weeks up to a maximum of 100 mcg. Titration was indicated for patients who could not achieve independence from active vitamin D and who could not reduce oral calcium to 500 mg or less per day. At end of treatment, 56% of subjects randomized to parathyroid hormone were receiving 100 mcg of parathyroid hormone per day, 26% were receiving 75 mcg of parathyroid hormone per day, and 18% were receiving 50 mcg of parathyroid hormone per day. Doses of co-administered active forms of vitamin D and calcium were adjusted (reduced or increased) to maintain albumin-corrected serum calcium within a desired target range throughout the trial in both arms.

For the efficacy analysis, subjects that fulfilled three components of a three-part response criterion were considered responders. A responder was defined as an individual who had: at least a 50% reduction from baseline in the dose of active vitamin D, at least a 50% reduction from baseline in the dose of oral calcium supplementation and an albumin-corrected total serum calcium concentration between 7.5 mg/dL and 10.6 mg/dL. At the end of treatment, significantly (p-value <0.001) more subjects treated with parathyroid hormone [46/84 (54.8%)] compared to placebo [1/40 (2.5%)] met the response criterion. Forty-two percent (35/84) of subjects randomized to parathyroid hormone were independent of active forms of vitamin D and were on no more than 500 mg of oral calcium, compared with 2.5% (1/40) of subjects randomized to placebo (p<0.001). There were no differences in the proportion of patients with a calcium level between 7.5 mg and 10.6 mg at end of treatment between subjects randomized to parathyroid hormone and placebo.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of parathyroid hormone (Natpara) meets the definition of medical necessity when ALL of the following criteria are met:

  1. Indication for use is hypoparathyroidism
  2. Member has a laboratory documented history of hypoparathyroidism as indicated by a parathyroid hormone (PTH) concentration below the lower limit of the normal laboratory reference range on two test dates at least 21 days apart within the past 12 months – laboratory documentation must be provided
  3. Member does not have a history of hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
  4. Member is refractory to an adequate trial of oral calcium (e.g., doses equal to or greater than 1000 mg/day)
  5. Member is refractory to an adequate trial of calcitriol (e.g., doses equal to or greater than 0.5 mcg/day)
  6. Treatment is prescribed or supervised by a board certified endocrinologist
  7. Member is age 18 years or older

Approval duration: 6 months

Continuation of parathyroid hormone (Natpara) meets the definition of medical necessity for members meeting the following criteria:

  1. The member has been previously approved by Florida Blue or another healthplan in the past 2 years, OR the member has previously met all indication-specific criteria for coverage
  2. Indication for use is hypoparathyroidism
  3. Member has demonstrated a beneficial response to treatment with parathyroid hormone

Approval duration: 6 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Dose should be individualized to achieve a serum calcium level in the lower half of the normal range.

• Confirm vitamin D stores are sufficient and serum calcium is above 7.5 mg/dL before starting treatment

• Starting dose is 50 mcg injected once daily in the thigh.

Dose Adjustments

• Decrease dose of active vitamin D by 50%, if serum calcium is above 7.5 mg/dL

• Monitor serum calcium levels every 3 to 7 days after starting or adjusting dose and when adjusting either active vitamin D or calcium supplements dose

Drug Availability

• For injection: 25 mcg, 50 mcg, 75 mcg, or 100 mcg

PRECAUTIONS:

Boxed Warning

Risk of osteosarcoma - Avoid use in patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma or patients with a history of prior external beam or implant radiation therapy involving the skeleton).

Contraindications

• None

Precautions/Warnings

• Potential Risk of Osteosarcoma – use is only for patients who cannot be well-controlled on calcium and active vitamin D. Avoid use in patients at increased risk for osteosarcoma.

• Severe Hypercalcemia – monitor serum calcium when starting or adjusting doses or when making changes to co-administered drugs known to raise serum calcium.

• Severe Hypocalcemia –may occur upon interruption or discontinuation of treatment. Monitor serum calcium and replace calcium and vitamin D.

• Digoxin Toxicity – hypercalcemia increases the risk of digoxin toxicity. Monitor serum calcium more frequently and increase monitoring when initiating or adjusting dose.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J3590

Unclassified biologics

C9399

Unclassified drugs or biologicals

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15)

E20.0

Idiopathic hypoparathyroidism

E20.8

Other hypoparathyroidism

E20.9

Hypoparathyroidism, unspecified

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: The following National Coverage Determination (NCD) was reviewed on the last guideline revised date: Self-administered Drug List (A54770). No Local Coverage Determination (LCD) was found at the time of the last guideline revised date.

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

None

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016-04-14]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016-04-14]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015-04-24]. Available from: http://clinicaltrials.gov/.
  4. Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2015-04-24]. Available from: http://www.thomsonhc.com/.
  6. NPS Pharmaceuticals, Inc. Natpara (parathyroid hormone) injection, powder, lyophilized, for solution. 2015 [cited 2016-04-14]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d11fba31-0a6c-11e3-8ffd-0800200c9a66 /.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016-04-14]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/11/16.

GUIDELINE UPDATE INFORMATION:

06/15/15

New Medical Coverage Guideline.

08/15/15

Revision to guideline; consisting of position statement.

11/01/15

Revision: ICD-9 Codes deleted.

06/15/16

Review and revision to guideline consisting of updating position statement, warnings and references.

Date Printed: December 17, 2017: 04:35 PM