BlueCross BlueShield of Tennessee Medical Policy Manual

Pulmonary Arterial Hypertension Agents

NDC CODE(S)

00703-1985-01 - Epoprostenol Sodium 0.5 MG SOLR (TEVA PARENTERAL MEDICINES)

00703-1995-01 - Epoprostenol Sodium 1.5 MG SOLR (TEVA PARENTERAL MEDICINES )

66215-0403-01 - Veletri 0.5 MG SOLR (ACTELION PHARMACEUTICALS)

66215-0402-01 - Veletri 1.5 MG SOLR (ACTELION PHARMACEUTICALS)

00173-0517-00 - Flolan 0.5 MG SOLR (GLAXO SMITH KLINE)

00173-0519-00 - Flolan 1.5 MG SOLR (GLAXO SMITH KLINE)

66302-0101-01 - Remodulin 1 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0102-01 - Remodulin 2.5 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0105-01 - Remodulin 5 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0110-01 - Remodulin 10 MG/ML SOLN (UNITED THERAPEUTICS CORP)

00069-0338-01 - Revatio 10 MG/12.5ML SOLN (PFIZER U.S)

66302-0206-01 - Tyvaso Starter 0.6 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0206-02 - Tyvaso Refill 0.6 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0206-03 - Tyvaso 0.6 MG/ML SOLN (UNITED THERAPEUTICS CORP)

66302-0206-04 - Tyvaso Starter 0.6 MG/ML SOLN (UNITED THERAPEUTICS CORP)

00069-0336-21 - Revatio 10 MG/ML SUSR (PFIZER U.S.)

00069-4190-68 - Revatio 20 MG TABS (PFIZER U.S.)

66302-0300-XX - Orenitram 0.125 MG TBCR (UNITED THERAPEUTICS CORP)*

66302-0302-XX - Orenitram 0.25 MG TBCR (UNITED THERAPEUTICS CORP)*

66302-0310-XX - Orenitram 1 MG TBCR (UNITED THERAPEUTICS CORP)*

66302-0325-XX - Orenitram 2.5 MG TBCR (UNITED THERAPEUTICS CORP)*

66302-0467-60 - Adcirca 20 MG TABS (LILLY)

61958-0801-XX - Letairis 5 MG TABS (GILEAD SCIENCES)*

61958-0802-XX - Letairis 10 MG TABS (GILEAD SCIENCES)*

66215-0101-XX - Tracleer 62.5 MG TABS (ACTELION PHARMACEUTICALS)*

66215-0102-XX - Tracleer 125 MG TABS (ACTELION PHARMACEUTICALS)*

66215-0501-XX - Opsumit 10 MG TABS (ACTELION PHARMACEUTICALS)*

50419-0250-XX - Adempas 0.5 MG TABS (BAYER HEALTHCARE PHARMA)*

50419-0251-XX - Adempas 1 MG TABS (BAYER HEALTHCARE PHARMA)*

50419-0252-XX - Adempas 1.5 MG TABS (BAYER HEALTHCARE PHARMA)*

50419-0253-XX - Adempas 2 MG TABS (BAYER HEALTHCARE PHARMA)*

50419-0254-XX - Adempas 2.5 MG TABS (BAYER HEALTHCARE PHARMA)*

66215-0602-XX - Uptravi 200 MCG TABS (ACTELION PHARMACEUTICALS)*

66215-0604-06 - Uptravi 400 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0606-06 - Uptravi 600 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0608-06 - Uptravi 800 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0628-20 - Uptravi 200 & 800 MCG TBPK (ACTELION PHARMACEUTICALS)

66215-0610-06 - Uptravi 1000 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0612-06 - Uptravi 1200 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0614-06 - Uptravi 1400 MCG TABS (ACTELION PHARMACEUTICALS)

66215-0616-06 - Uptravi 1600 MCG TABS (ACTELION PHARMACEUTICALS)   

66215-0302-00 - Ventavis 10 MCG/ML SOLN (ACTELION PHARMACEUTICALS)

66215-0302-30 - Ventavis 10 MCG/ML SOLN (ACTELION PHARMACEUTICALS)

66215-0303-00 - Ventavis 20 MCG/ML SOLN (ACTELION PHARMACEUTICALS)

66215-0303-30 - Ventavis 20 MCG/ML SOLN (ACTELION PHARMACEUTICALS)

00173-0857-02 - Sterile Diluent Flolan pH 12 SOLN (GLAXO SMITH KLINE)

 

 

 

*Multiple package sizes available

DESCRIPTION

Pulmonary arterial hypertension (PAH) is a rare, progressive disorder. Early symptoms of PAH include dyspnea during exercise, chest pain, and fainting episodes. The exact cause of PAH is unknown and although treatable, there is no known cure for the disease. PAH typically affects females between 30-60 years of age and affects females twice as frequently as males. The individual with PAH may go without diagnosis for years due to mild, non-specific complaints, only present during demanding exercise. However, diagnosis and treatment is vital, as the untreated high blood pressure in the lungs may lead to heart failure. The progressive nature of this disease means that an individual may initially experience only mild symptoms, but will eventually require medical care to maintain a normal lifestyle.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

Reference Charts:

 

Inadequate Clinical Response Criteria

 

Inadequate clinical response for patients who were initially in WHO Functional Class II or III:

 
  • Resulting clinical status defined as stable and not satisfactory

 

OR

 
  • Resulting clinical status defined as unstable and deteriorating

 

Inadequate clinical response for patients who were initially in WHO Functional Class IV:

 
  • No rapid improvement to WHO Functional Class III or better

 

OR

 
  • Resulting clinical status defined as stable and not satisfactory

 

WHO Classification of Pulmonary Hypertension (PH)

Group 1 PAH

Pulmonary arterial hypertension (PAH)

Group 2 PH

Pulmonary hypertension owing to left heart disease

Group 3 PH

Pulmonary hypertension owing to lung diseases and/or hypoxia

Group 4 PH

Chronic thromboembolic pulmonary hypertension (CTEPH)

Group 5 PH

Pulmonary hypertension with unclear multifactorial mechanisms

RENEWAL CRITERIA

INDICATION(S) DOSAGE & ADMINISTRATION
Revatio™ (oral tablet or suspension) 20 mg three times a day, 4-6 hours apart.
Revatio™ (intravenous injection) 10 mg (12.5 mL) three times a day administered as an intravenous bolus injection
Adcirca® (oral tablet) 40 mg (two 20 mg tablets) once daily. (Dividing the dose (40 mg) over the course of the day is not recommended). May be given in combination with Letairis
Flolan®/Veletri (continuous intravenous infusion)

Increase in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established.

Epoprostenol must be infused via a central venous catheter
Remodulin (continuous intravenous infusion)

1.25 ng/kg/min (or 0.625 ng/kg/min if not tolerated); dose increase based on clinical response (increments of 1.25 ng/kg/min per week for the first 4 weeks of treatment, later 2.5 ng/kg/min per week).

Orenitram™ (oral tablet)

Starting dose: 0.25 mg by mouth twice daily or 0.125 mg three times daily. Titrate by 0.25 mg or 0.5 mg twice daily or 0.125 mg three times daily, not more than every 3 to 4 days as tolerated. Maximum dose is determined by tolerability.

Transitioning from SC/IV routes of treprostinil (Remodulin):

• Orenitram total daily dose (mg) = 0.0072 X Remodulin dose (ng/kg/min) X weight (kg)

• Decrease the dose of Remodulin while simultaneously increasing the dose of Orenitram. The Remodulin dose can be reduced up to 30 ng/kg/min per day and dose of Orenitram simultaneously increased up to 6 mg per day (2 mg TID) if tolerated.

Tyvaso® (oral inhalation)

3 breaths (18 mcg) orally via the Tyvaso Inhalation System 4 times daily. Dose is titrated by an additional 3 breaths at approximately 1- to 2-week intervals to eventually reach 9 breaths (54 mcg) per treatment session administered 4 times daily if tolerated. (1 ampule contains sufficient medication for all 4 treatment sessions in a single day)

Ventavis® (oral inhalation)

Initially, 2.5 mcg delivered at the mouthpiece via I-neb AAD system and if well tolerated, the dose may be increased and maintained at 5 mcg administered 6 to 9 times daily, but no more than every 2 hours, during waking hours based on individual need and tolerability. Max daily dose is 45 mcg (5 mcg administered 9 times per day). (1 ampule should be used for each dose; the 20 mcg/mL strength is intended to decrease treatment times in patients who experience extended treatment times )

Letairis™ (oral tablet)

Initiate at 5 mg daily, with or without tadalafil 20mg daily. At 4-week intervals, either the dose of Letairis or tadalafil can be increased, as needed and tolerated, to Letairis 10 mg or tadalafil 40mg.

Tracleer® (oral tablet)

Initiate at 62.5 mg twice daily with or without food for 4 weeks, and then increase to 125 mg twice daily. (Patients <40 kg – initial and maintenance dose is 62.5 mg twice daily)

Opsumit (oral tablet)

10 mg once daily for oral administration

Adempas (oral tablet)

Initiate treatment at 1mg taken three times a day. For patients who may not tolerate the hypotensive effect, consider starting dose of 0.5 mg three times a day. Dosage may be increased by 0.5mg at intervals of no sooner than 2-weeks as tolerated to a maximum of 2.5mg three times a day.

Uptravi

Recommended starting dose is 200 mcg twice daily. Increase the dose in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily.

*tolerability may be improved when taken with food

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Ambrisentan. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Epoprostenol. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Iloprost. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Macitentan. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Riociguat. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Selexipag. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Sildenafil. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Tadalafil. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2016, November). Treprostinil. Retrieved November 30, 2016 from MICROMEDEX Healthcare Series.

U. S. Food and Drug Administration. (2012, June). Center for Drug Evaluation and Research. Veletri® (epoprostenol). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022260s005lbl.pdf.

U. S. Food and Drug Administration. (2013, November). Center for Drug Evaluation and Research. Ventavis® (iloprost). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021779s014lbl.pdf.

U. S. Food and Drug Administration. (2014, December). Center for Drug Evaluation and Research. Remodulin® (treprostinil). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021272s019lbl.pdf.

U. S. Food and Drug Administration. (2014, May). Center for Drug Evaluation and Research. Adempas® (riociguat). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204819s002lbl.pdf.

U. S. Food and Drug Administration. (2015, April). Center for Drug Evaluation and Research. Adcirca® (tadalafil). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022332s007lbl.pdf.

U. S. Food and Drug Administration. (2015, April). Center for Drug Evaluation and Research. Flolan® (treprostinil). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020444s021lbl.pdf.

U. S. Food and Drug Administration. (2015, April). Center for Drug Evaluation and Research. Revatio® (sildenafil). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021845s016,022473s010,203109s009lbl.pdf.

U. S. Food and Drug Administration. (2015, December). Center for Drug Evaluation and Research. Uptravi® (selexipag). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207947s000lbl.pdf.

U. S. Food and Drug Administration. (2015, October). Center for Drug Evaluation and Research. Letairis® (ambrisentan). Retrieved November 30, 2016 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022081s033lbl.pdf.

U. S. Food and Drug Administration. (2016, January). Center for Drug Evaluation and Research. Orenitram® (treprostinil). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203496s002lbl.pdf.

U. S. Food and Drug Administration. (2016, June). Center for Drug Evaluation and Research. Opsumit® (macitentan). Retrieved November 30, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204410s008lbl.pdf.

U. S. Food and Drug Administration. (2016, June). Center for Drug Evaluation and Research. Tyvaso® (treprostinil). Retrieved December 1, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022387s014lbl.pdf.

ORIGINAL EFFECTIVE DATE:  6/1/2002

MOST RECENT REVIEW DATE:  5/9/2017

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

Pharmaceutical Decision Support Tree

Pulmonary Arterial Hypertension Agents -  ambrisentan (Letairis™), bosentan (Tracleer®), epoprostenol (Flolan®/Veletri®), iloprost (Ventavis®), macitentan (Opsumit®), riociguat (Adempas®), selexipag (Uptravi®), sildenafil (Revatio™), tadalafil (Adcirca®) and treprostinil (Orenitram™, Remodulin®, Tyvaso®)

  1. Is this the initial request for the agent?

If yes, go to question #2

If no, go to question #14

  1. Does the individual have a diagnosis of pulmonary arterial hypertension (PAH) and is 18 years of age or older (unless the requested product is specifically Remodulin®, then 16 years of age or older)?

If yes, go to question #3

If no, go to question #7

  1. Is the diagnosis confirmed by documented right heart catheterization with mean pulmonary artery pressure (mPAP) > 25mm Hg?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there documentation of ALL of the following?

If yes, go to question #5

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for monotherapy?

If yes, go to question #6

If no, go to question #10

  1. Is the individual designated as New York Heart Association (NYHA) or World Health Organization (WHO) functional class of ANY ONE of the following as (see policy for chart)?

If yes, go to question #7

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual of reproductive potential have a negative pregnancy test prior to start of therapy and is enrolled in the manufacturer’s REMS program (Opsumit®, Letairis, Tracleer® and Adempas® ONLY)?

If yes, go to question #14

If no, this does not meet medical necessity and/or medical appropriateness criteria

If not applicable, go to question #14

  1. Does the individual have a diagnosis of Chronic-Thromboembolic Pulmonary Hypertension and the requested agent is riociguat (Adempas®)?

If yes, go to question #9

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the individual 18 years of age or older with ALL of the following?

If yes, go to question #10

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual have ANY ONE of the following?

If yes, go to question #11

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there documentation that treatment will NOT be used in combination with ANY ONE of the following?

If yes, go to question #12

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for combination therapy for pulmonary arterial hypertension for ANY ONE of the following?

If yes, go to question #13

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the combination therapy regimen is limited to a two drug regimen from two different therapeutic classes as listed below (unless otherwise specified)?

If yes, go to question #14

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for ANY ONE of the following?

INDICATION(S)

BILLABLE UNITS

Medical Benefit Only

DOSAGE & ADMINISTRATION
Revatio™ (oral tablet or suspension)   20 mg three times a day, 4-6 hours apart.
Revatio™ (IV injection) 3 billable units per day 10 mg (12.5 mL) three times a day administered as an intravenous bolus injection
Adcirca® (oral tablet)   40 mg (two 20 mg tablets) once daily. (dividing the dose (40 mg) over the course of the day is not recommended). May be given in combination with Letairis
Flolan®/Veletri (continuous intravenous infusion) 6 billable units per day

Increase in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established.

Epoprostenol must be infused via a central venous catheter
Remodulin (continuous IV infusion) 7 billable units per day

1.25 ng/kg/min (or 0.625 ng/kg/min if not tolerated); dose increase based on clinical response (increments of 1.25 ng/kg/min per week for the first 4 weeks of treatment, later 2.5 ng/kg/min per week).

Orenitram™ (oral tablet)  

Starting dose: 0.25 mg by mouth twice daily or 0.125 mg three times daily. Titrate by 0.25 mg or 0.5 mg twice daily or 0.125 mg three times daily, not more than every 3 to 4 days as tolerated. Maximum dose is determined by tolerability.

Transitioning from SC/IV routes of treprostinil (Remodulin):

• Orenitram total daily dose (mg) = 0.0072 X Remodulin dose (ng/kg/min) X weight (kg)

• Decrease the dose of Remodulin while simultaneously increasing the dose of Orenitram. The Remodulin dose can be reduced up to 30 ng/kg/min per day and dose of Orenitram simultaneously increased up to 6 mg per day (2 mg TID) if tolerated.

Tyvaso® (oral inhalation) 1 billable unit per day

3 breaths (18 mcg) orally via the Tyvaso Inhalation System 4 times daily. Dose is titrated by an additional 3 breaths at approximately 1- to 2-week intervals to eventually reach 9 breaths (54 mcg) per treatment session administered 4 times daily if tolerated. (1 ampule contains sufficient medication for all 4 treatment sessions in a single day)

Ventavis® (oral inhalation) 1 billable unit per day

Initially, 2.5 mcg delivered at the mouthpiece via I-neb AAD system and if well tolerated, the dose may be increased and maintained at 5 mcg administered 6 to 9 times daily, but no more than every 2 hours, during waking hours based on individual need and tolerability. Max daily dose is 45 mcg (5 mcg administered 9 times per day). (1 ampule should be used for each dose; the 20 mcg/mL strength is intended to decrease treatment times in patients who experience extended treatment times )

Letairis™ (oral tablet)  

Initiate at 5 mg daily, with or without tadalafil 20mg daily. At 4-week intervals, either the dose of Letairis or tadalafil can be increased, as needed and tolerated, to Letairis 10 mg or tadalafil 40mg.

Tracleer® (oral tablet)  

Initiate at 62.5 mg twice daily with or without food for 4 weeks, and then increase to 125 mg twice daily. (Patients <40 kg – initial and maintenance dose is 62.5 mg twice daily)

Opsumit (oral tablet)  

10 mg once daily for oral administration

Adempas (oral tablet)  

Initiate treatment at 1mg taken three times a day. For patients who may not tolerate the hypotensive effect, consider starting dose of 0.5 mg three times a day. Dosage may be increased by 0.5mg at intervals of no sooner than 2-weeks as tolerated to a maximum of 2.5mg three times a day.

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual continue to meet individual approval criteria in questions 2 through 14?

If yes, go to question #16

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is response to treatment indicated by ANY ONE of the following?

If yes, go to question #17

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is treatment with ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.