Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Treatment of Pulmonary Artery Hypertension with Intravenous, Subcutaneous, and Inhaled Pharmacologic Agents

Policy #:08.00.25j

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. MEDICALLY NECESSARY

Epoprostenol (Flolan®, Veletri®), intravenous infusion, is considered medically necessary and, therefore, covered, when all of the following criteria are met:
  • The individual has a confirmed diagnosis of pulmonary arterial hypertension (PAH), in accordance with the World Health Organization (WHO) Group 1 classification.
    • The diagnosis of PAH has been confirmed by a catherization (right heart or Swan-Ganz) or echocardiography.
  • Documentation that the individual's mean pulmonary arterial pressure is greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise/exertion.
  • The individual meets the New York Heart Association (NYHA) Functional Classification requirement of Class III-IV.

Treprostinil sodium (Remodulin®), intravenous or subcutaneous infusion, is considered medically necessary and, therefore, covered when all of the following criteria are met:
  • The individual has a confirmed diagnosis of PAH, in accordance with the WHO Group 1 classification.
    • The diagnosis of PAH has been confirmed by a catherization (right heart or Swan-Ganz) or echocardiography.
  • Documentation that the individual's mean pulmonary arterial pressure is greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise/exertion.
  • The individual meets the NYHA Functional Classification requirement of Class II-IV.

Iloprost (Ventavis®) and Treprostinil, (Tyvaso®), inhalation, is considered medically necessary and, therefore, covered when all of the following criteria are met:
  • The individual has a confirmed diagnosis of PAH, in accordance with the WHO Group 1 classification.
    • The diagnosis of PAH has been confirmed by a catherization (right heart or Swan-Ganz) or echocardiography.
  • Documentation that the individual's mean pulmonary arterial pressure is greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise/exertion.
  • The individual meets the NYHA Functional Classification requirement of Class III-IV.


EXPERIMENTAL/INVESTIGATIONAL

All other uses for epoprostenol (Flolan®), treprostinil (Remodulin®), Veletri® (epoprostenol), Ventavis® (iloprost), and Tyvaso® (treprostinil) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

NOT ELIGIBLE FOR SEPARATE REIMBURSEMENT

The Company covers the use of intravenous (IV) fluids for the preparation (e.g., dilution, reconstitution) of pharmaceuticals, biologics, and other substances for IV administration; however, such use is considered to be integral to the administration of the pharmaceutical, biologic, or other substance and is, therefore, not eligible for reimbursement. Participating providers may not bill members for this service.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

The World Health Organization (WHO) Group 1 Classification

Pulmonary arterial hypertension (PAH) represents Group 1 within the Pulmonary Hypertension World Health Organization (WHO) clinical classification system and is one of five such groups. The groups are divided based on etiology.
  • Idiopathic (IPAH): a rare form of PAH characterized by elevated pulmonary artery pressure with no apparent cause.
  • Heritable (HPAH): a form of PAH caused by predisposing genes or from a familial context.
    • Bone morphogenetic protein receptor type 2 (BMPR2)
    • Activin receptor-like kinase 1 gene (ALK1), endoglin (with or without haemorrhagic telangiectasia)
    • Unknown
  • Drug- and toxin-induced
  • Associated with (APAH)
    • Connective tissue diseases
    • Human immunodeficiency virus (HIV) infection
    • Portal hypertension
    • Congenital heart disease (CHD)
    • Schistosomiasis
    • Chronic haemolytic anemia
  • Persistent pulmonary hypertension of the newborn (PPHN)
Unique class 1 (Group 1)
  • Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)

The New York Heart Association (NYHA) Functional Classifications are summarized as follows:

Class I: Individuals with no limitation of physical activity and no symptoms. Ordinary physical activity does not cause undue fatigue, palpitations, or dyspnea (shortness of breath).

Class II: Individuals with slight limitation of physical activity and mild symptoms. Comfortable at rest. Ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.

Class III: Individuals with marked limitation of physical activity due to symptoms. Comfortable at rest, but less than ordinary activity causes fatigue, palpitations, dyspnea, or anginal pain.

Class IV: Individuals with severe limitations experience symptoms of heart failure or the anginal syndrome that may be present even while at rest. If any physical activity is undertaken, discomfort is increased.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, epoprostenol (Flolan®) and treprostinil (Remodulin®) are covered under the medical benefit of the Company’s products when the medical necessity criteria listed in this medical policy are met.

A medication or class of medications may be a product or group contract exclusion. Individual benefits must be verified.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

All pharmacologic agents listed in this medical policy have US Food and Drug Administration approval for the treatment of PAH.

Description

DESCRIPTION AND ETIOLOGY OF PULMONARY ARTERIAL HYPERTENSION (PAH)

Pulmonary arterial hypertension (PAH) (also referred to as pulmonary hypertension [PH] or primary or secondary pulmonary hypertension [PPH, SPH]) is a progressive disorder characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, which carries blood from the heart to the lungs. Hypertension occurs when most of the small arteries throughout the lungs narrow in diameter, increasing resistance to blood flow through the lungs. To overcome the increased resistance, pressure intensifies in the pulmonary artery and in the right ventricle that pumps blood into the pulmonary artery. The right side of the heart is forced to work harder against this increased pressure, and, over time, this heightened work load causes the right side of the heart to become enlarged and can progress to right-sided heart failure (cor pulmonale). The National Institutes of Health (NIH) registry working group has defined PAH as a mean pulmonary artery pressure >25 mm Hg at rest or 30 mm Hg with exercise and no known or proven etiology. There are two main methods used to measure pulmonary artery (PA) pressures: trans-thoracic echocardiogram (TTE) and right heart catheterization.

Signs and symptoms of the presence of PAH occur when increased pressure cannot fully overcome the elevated resistance, resulting in insufficient blood flow to the body and its organs. The most frequently reported symptom of PAH is dyspnea of exertion (DOE), and the person may report periods of fainting. As the condition worsens, other symptoms, such as dizziness, swelling (edema) of the ankles or legs, overall muscle weakness, chest pain, cyanosis of the skin and/or lips, and heart palpitations, are reported.

THE WORLD HEALTH ORGANIZATION (WHO) CLASSIFICATION OF PULMONARY HYPERTENSION (PH)

PAH is one subset of the larger disease category of pulmonary hypertension (PH). PH is a general term used to describe a chronic, progressive condition characterized by high pulmonary vascular pressure in the lungs. The World Health Organization (WHO) developed a 5-group classification system for PH based upon disease etiology. The individuals in WHO Group 1 are considered to have PAH, whereas those in the remaining Group 2--Group 5 are considered to have PH. However, when the groups are discussed collectively, the term PH is used.

OVERALL TREATMENT OF PAH

The treatment of PAH is highly individualized. The goals of PAH treatment consist of symptom improvement, enhanced functional capacity, reversal or prevention of disease worsening, and prevention of hospitalization. Therapy to control PAH consists of diet, exercise, and pharmacologic treatment. Oxygen and medications such as anticoagulants, diuretics, and digoxin are used initially to treat the underlying cause of PAH. In more advanced disease, medications such as calcium channel blockers, intravenous (IV) or inhaled prostanoids (e.g., epoprostenol), endothelin receptor antagonists (e.g., bosentan), or phosphodiesterase 5 inhibitors (e.g. sildenafil) are used as monotherapy or in combination.

AGENTS ADMINISTERED VIA INTRAVENOUS ROUTE

EPOPROSTENOL (FLOLAN®)
Epoprostenol (Flolan®) is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. It is indicated for the treatment of pulmonary arterial hypertension (WHO Group 1) to improve exercise capacity in individuals with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases.

EPOPROSTENOL (VELETRI®)
Veletri® (epoprostenol) is a potent vasodilator intended for the treatment of pulmonary artery hypertension (PAH) to improve exercise capacity. During clinical trials, data demonstrating efficacy was obtained predominantly from individuals with NHYA Functional Class III-IV symptoms with etiology from idiopathic or inherited PAH or PAH associated with connective tissue diseases. Veletri® (epoprostenol) is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.

AGENTS ADMINISTERED VIA INTRAVENOUS OR SUBCUTANEOUS INFUSION

TREPROSTINIL (REMODULIN®)
Treprostinil (Remodulin®) is a prostacyclin that causes direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. It is indicated in the treatment of pulmonary arterial hypertension (WHO Group 1) in individuals with NYHA Class II-IV symptoms. Treprostinil (Remodulin®) is administered as a continuous infusion via a self-inserted subcutaneous catheter using an infusion pump designed for subcutaneous drug delivery. Continuous subcutaneous infusion (undiluted) is the preferred mode of delivery. Intravenous infusion (with dilution required), is reserved for those who cannot tolerate continuous subcutaneous infusion.

AGENTS ADMINISTERED VIA INHALATION

ILOPROST (VENTAVIS®) INHALATION SOLUTION
Ventavis® (iloprost) inhalation solution is indicated for the treatment of pulmonary arterial hypertension to improve exercise tolerance and NYHA symptoms and prevent deterioration. During clinical trials, data demonstrating efficacy was obtained mostly from individuals with NYHA Functional Class III-IV symptoms who had idiopathic or inherited PAH or PAH associated with connective tissue diseases. Ventavis® is administered via an I-neb® Adaptive Aerosol Delivery (AAD) system typically obtained from a specialized pharmacy. The I-neb® ADD nebulizer is not the same type of device that is commonly used to deliver nebulized medications for conditions such as asthma.

TREPROSTINIL (TYVASO®) INHALATION SOLUTION
Tyvaso® (treprostinil) inhalation solution is a prostacyclin vasodilator indicated for the treatment of PAH (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately individuals with NHYA Functional Class III symptoms with etiologies of idiopathic or inherited PAH or PAH associated with connective tissue diseases. Tyvaso® is given by oral inhalation only via a special nebulizing device, the Optineb®, and its accessories; the Optineb® is typically obtained from a specialized pharmacy. The Optineb® is not the same type of device that is commonly used to deliver nebulized medications for conditions such as asthma.

COMPARISON OF PRODUCTS

DrugRoute of Administration NYHA Functional Class Symptoms
Flolan® (epoprostenol) *Continuous intravenous infusion Class III and Class IV
Veletri® (epoprostenol) * Continuous intravenous infusion Class III and Class IV
Remodulin® (treprostinil) *Continuous intravenous or subcutaneous infusion Class II, Class III, Class IV
Ventavis® Inhalation Solution (iloprost) *Inhaled Class III and Class IV
Tyvaso® Inhalation Solution (treprostinil)*Inhaled Class III
*Safety and effectiveness in the pediatric population have not been established.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Actelion Pharmaceuticals Ltd. Diagnosing PAH. Last updated: August 2013. Available at: http://www.pah-info.com/diagnosing-pah. Accessed March 7, 2017.

American Heart Association. Heart failure classification. [American Heart Association Web site]. 09/14/14. Available at:http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-Failure_UCM_306328_Article.jsp. Accessed March 7, 2017.s

Dugdale D, Hadjiliadis, D, Pulmonary Hypertension. 10/09/14. Medline Plus Web site. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000112.htm. Accessed March 7, 2017.

Epoprostenol (Flolan®). Micromedex® Healthcare Series. [Micromedex® Web site]. Last modified 8/21/2014. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 7, 2017.

Hopkins W, Rubin L. Treatment of pulmonary hypertension in adults. Wolters Kluwer Health. [Up to Date Web site]. Sept 2014. Available at: http://www.uptodate.com [via subscription only]. Accessed March 7, 2017.

McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-619.

Rubin L, Hopkins W. Overview of pulmonary hypertension in adults. Wolters Kluwer Health. [UpToDate Web site]. July 2012. Available at: http://www.uptodate.com [via subscription only]. Accessed March 7, 2017.

Ronald J. Oudiz RJ, Rubin LJ. Exercise-Induced Pulmonary Arterial Hypertension. A New Addition to the Spectrum of Pulmonary Vascular Diseases. Circulation. November 17, 2008; 118:2120-2121. Available at: http://circ.ahajournals.org/content/118/21/2120. Accesses March 7, 2017.

Rubin L, Hopkins W. Treatment of pulmonary hypertensin in adults. Wolters Kluwer Health. [UpToDate Web site]. July 2-12. Available at: http://www.uptodate.com [via subscription only]. Accessed March 7, 2017.

Treprostinil (Remodulin®). Micromedex® Healthcare Series. [Micromedex® Web site]. Last modified 10/13/2014. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 7, 2017.

United Therapeutics. Tyvaso® (treprostinil) Product Information. Breathe in the Power of a Prostanoid. 02/2014. Available at: http://www.tyvaso.com/dtc. Accessed March 7, 2017.

US Food and Drug Administration. Center for Drug Evaluation and Research. Drugs @FDA. Approval letter for Epoprostenol. Available at:http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022260s000ltr.pdf. Accessed March 7, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Remodulin® (treprostinil sodium) injection. Accelerated and Restricted Approvals Under Subpart H (drugs) and Subpart E (biologics)labeling. [FDA Web site]. Approval date: 5/21/02. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-272_Remodulin.cfm. Accessed March 7, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Remodulin® (treprostinil sodium) injection labeling. [FDA Web site]. September 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-272_Remodulin.cfm. Accessed March 7, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Flolan® (epoprostenol sodium). Detailed view: Safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER) -- March 2008. [FDA Web site]. 07/12/09. Available at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm116457.htm. Accessed March 7, 2017.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

I27.0 Primary pulmonary hypertension

I27.20 Pulmonary hypertension, unspecified

I27.21 Secondary pulmonary arterial hypertension

I27.22 Pulmonary hypertension due to left heart disease

I27.23 Pulmonary hypertension due to lung diseases and hypoxia

I27.24 Chronic thromboembolic pulmonary hypertension

I27.29 Other secondary pulmonary hypertension

I27.83 Eisenmenger's syndrome

P29.30 Pulmonary hypertension of newborn




HCPCS Level II Code Number(s)

J1325 Injection, epoprostenol, 0.5 mg


J3285 Injection, treprostinil, 1 mg

J7686 Treprostinil, inhalation solution, FDA-approved final product, noncompounded, administered through DME, unit dose form, 1.74 mg

Q4074 Iloprost, inhalation solution, FDA-approved final product, noncompounded, administered through DME, unit dose form, up to 20 mcg

S0155 Sterile dilutant for epoprostenol, 50 ml

S9061 Home administration of aerosolized drug therapy (e.g., Pentamidine); administrative services, professional pharmacy services, care coordination, all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9347 Home infusion therapy, uninterrupted, long-term, controlled rate intravenous or subcutaneous infusion therapy (e.g., epoprostenol); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Effective 10/05/2017 this policy has been updated to the new policy template
format.
Version Effective Date: 10/01/2017
Version Issued Date: 09/29/2017
Version Reissued Date: N/A

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