Post-market Review of Pulmonary Arterial Hypertension (PAH) Medicines

Page last updated: 3 February 2023


Every effort has been made to ensure web accessibility to the Post-market Review of Pulmonary Arterial Hypertension medicines, however complete web accessibility cannot be guaranteed.  If you have trouble accessing information within the report and you would like a copy to be provided to you, please direct all queries via email to PBS postmarket.


Pulmonary Arterial Hypertension (PAH) is a type of high blood pressure that arises when the arteries on the right side of the heart that supply blood to the lungs (pulmonary arteries) thicken and become rigid.  When the pulmonary arteries thicken, the heart needs to work harder to provide adequate blood flow to the lungs, meaning that the body may not get all the oxygen it needs to function well. Patients with PAH can experience shortness of breath, dizziness, chest pain and fatigue.

A PAH diagnosis is confirmed by detection of high blood pressure in the pulmonary artery and the severity of disease is classified by its impact on physical activity. The PAH World Health Organization (WHO) Functional Class classification of symptoms is used to define the severity of disease as experienced by patients, as summarised in Table 1.

Table 1. Summary of PAH WHO Functional Class classification of symptoms

PAH WHO Functional Class*

Description of symptoms

1 (I)

No symptoms of PAH during physical activity or when at rest.

2 (II)

Symptoms occur during normal physical activity but not when at rest.

3 (III)

Symptoms occur during normal and minor physical activity but not when at rest.

4 (IV)

Symptoms occur with any physical activity and when at rest.

*Functional Class 1, 2, 3 and 4 is referred to in international guidelines, and also the PBS criteria, using Roman Numerals (shown in brackets: I, II, III, IV).  

In February 2015, the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee (PBAC) reviewed the Pharmaceutical Benefits Scheme (PBS) utilisation of PAH medicines. The DUSC considered that the PBS restrictions for PAH medicines were not consistent with current treatment guidelines as:

  • Patients with PAH WHO Functional Class (FC) III symptoms with a mean right arterial pressure of 8 mm Hg or less were required to trial -at least six weeks of appropriate vasodilator medicine without an adequate response before accessing a PAH.
  • Treatment of patients with PAH WHO FC II symptoms was not allowed.
  • Combination therapy was not subsidised.

In July 2015, the PBAC considered a submission from the sponsor of bosentan, epoprostenol and macitentan to remove the requirement for patients to be assessed as having achieved a response to treatment for continuing access to these medicines. The submission claimed that the PBS restriction requiring ongoing evidence of improvement or stability in disease status was inconsistent with best clinical practice and international guidelines. The submission further argued that in the case of an inadequate response to initial therapy, guidelines recommended sequential combination therapy, rather than cessation or switching between therapies as was required by the PBS restrictions. Noting the submission’s claim that the PBS continuing restriction for PAH medicines was inconsistent with best clinical practice and international guidelines, the PBAC considered that there were several issues around PAH medicines that could not be assessed within the scope of the submission.

Further information is available in the July 2015 PBAC Public Summary Documents  for the combined bosentan, epoprostenol and macitentan submission.

In December 2015, the PBAC recommended a Post-market Review (PMR) of the efficacy and cost‑effectiveness of PAH medicines, including the existing listings for patients with WHO FC III and IV symptoms, and the expanded use of these therapies as recommended in international guidelines.

The purpose of the PMR was to review the safety, efficacy (treatment benefit) and cost-effectiveness of these medicines, in the context of patient access to optimal treatment and Quality Use of Medicines. 

The PMR was approved by the then Minister for Health on 7 April 2016 and was carried out under the Australian Government’s post-market monitoring program, which aims to ensure the continued safe, cost-effective and Quality Use of Medicines listed on the PBS.

Medicines included in the PAH Review were:

Table 1. PBS-listed PAH medicines included in the PMR*

Medicine Class

PBS listed medicines

generic drug name

endothelin receptor antagonists (ERAs)

ambrisentan, bosentan monohydrate, macitentan

phosphodiesterase type 5 inhibitors (PDE-5i)

sildenafil, tadalafil


epoprostenol sodium, iloprost

soluble guanylate cyclase stimulators (sGC stimulator)


Selexipag, first PBS-listed 1 February 2021, was not included in the PMR.


Reference Group


Nominating Body



Professor Terence Campbell



Pharmaceutical benefits policy, cardiology

Professor Anna Kemp-Casey


Individual - Technical Expert

Drug utilisation

Professor Susanna Proudman

Individual - Technical Expert

Pulmonary disease

Professor Trevor Williams

Individual - Technical Expert

Pulmonary disease

Ms Michelle Tew

Australian Health Economics Society

Technical Expert

Health economics

Dr Eugene Kotlyar

Cardiac Society of Australia and New Zealand

Organisational representative

Cardiac disease

Professor Garry Jennings

Heart Foundation

Organisational representative


Ms Elizabeth De Somer

Dr Vicki Gardiner

Medicines Australia

Organisational representative

Pharmaceutical Industry

Professor Geoff Strange

Pulmonary Hypertension Society of Australia and New Zealand

Organisational representative

Pulmonary disease

Dr Charlotte Hespe

Royal Australian College of General Practitioners

Organisational representative

General practice

Mr Garth Birdsey

Society of Hospital Pharmacists

Organisational representative

Hospital pharmacy

Dr Jane Cook

Dr Grant Pegg

Therapeutic Goods Administration

Organisational representative

Regulation and safety of medicines

Dr Jeremy Wrobel

Thoracic Society of Australia and New Zealand

Organisational representative

Pulmonary disease

Dr Christine Walker

Consumers’ Health Forum

Organisational representative

Health consumer advocacy

Final Terms of Reference

The PBAC considered the draft Review Terms of Reference (ToR) and comments from stakeholders at the August 2016 PBAC special meeting. Following the August 2016 PBAC special meeting the then Minister for Health approved the final Terms of Reference for the Review:

  1. Review recent clinical guidelines for the management of PAH and compare this to the PBS restrictions and Therapeutic Goods Administration (TGA) indications for the use of PAH medicines.
  2. Review the utilisation of PAH medicines in Australia, including sources of data that can provide additional information on clinical use that is not available from PBS data.
  3. Review the clinical outcomes that are most important or clinically relevant to patients with PAH, and the extent to which these outcomes are included in the evidence previously considered by PBAC.
  4. Collate and evaluate evidence on the comparative effectiveness of PAH medicines, including combination use and use in the WHO functional class II patient populations.
  5. Following ToR 1-4 consider reviewing the cost-effectiveness of existing PBS listings for PAH medicines, and in treatment of WHO functional class II and combination treatment in class III and class IV patients.

Public Submissions addressing the final Terms of Reference (closed)

The public submission process for the Pulmonary Arterial Hypertension (PAH) Medicines Review was open between 13 February 2017 and 27 March 2017. To view submissions please go to the Public Consultation page

Consumer Session

A consumer session was held in Sydney on 14 October 2017 with members of the Pulmonary Hypertension Association Australia (PHAA).  To view the Consumer Outcome Statement please go to the Public Consultation page.

Public Consultation on the Draft Review Report (closed)

Public Consultation on the draft Review Report was open between 21 May 2018 and 10 June 2018.

Post-market Review of PAH Medicines – Final Report to the PBAC

The Final Report is provided in ten parts in DOCX and PDF format. ‘Commercial-in-confidence information has been redacted.

  1. Executive Summary (PDF  1797 KB) - (Word 290 KB)
  2. Background and Term of Reference 1 (PDF  3193 KB) - (Word 2021 KB)
  3. Term of Reference 2 (PDF 1473 KB) - (Word 392 KB)
  4. Appendix 2A (PDF 1473 KB) - (Word 1466 KB)
  5. Appendix 2B (PDF 605 KB) - (Word 392 KB)
  6. Appendix 2C (PDF 1225 KB) - (Word 213 KB)
  7. Term of Reference 3 (PDF 1025 KB) - (Word  61 KB)
  8. Appendix 3A (PDF 475 KB) - (Word 45 KB)
  9. Term of Reference 4 (PDF 4731 KB) - (Word 1315 KB)
  10. Term of Reference 5 (PDF 864 KB) - (Word 67 KB)

PBAC Consideration of the Final Report

The PBAC considered the PMR of PAH Final Report in November 2018, including PBAC sub-committee advice and stakeholder comments. Parts of the PBAC Minutes have been redacted due to ‘Commercial-in-confidence’ information.

PBAC Consideration of PBS PAH medicine restriction changes arising from the Post-market Review

Over several meetings between March 2019 and March 2022, the PBAC considered and recommended changes to PBS restrictions for PAH medicines to improve patient access and align PBS restrictions more closely with clinical guidelines.

Parts of the PBAC minutes have been redacted due to ‘Commercial-in-confidence’ information.

Plain Language Summary

A brief plain language summary  (PDF 204 KB)(Word 41 KB) of PMR outcomes for consumers is available.

Review Process

This Review followed the Post-market Review Framework available on the Reviews website. This process included public consultation on the draft Terms of Reference, an opportunity to provide submissions to the Review, and an opportunity to comment on the draft Review Report.

Further Information

Further information on post-market reviews is available on the Reviews website.

Subscribe to news updates for the latest information regarding reviews, including public consultation, and publication of review reports.