Hospital Circular 04/2004: Hospital Circulars - Department of Health, Victoria, Australia

Hospital Circular 04/2004

Date Issued: 9 February 2004

Distribution: Public Hospitals

Subject: Highly Specialised Drugs Program

Purpose: To advise hospitals of changes to the Highly Specialised Drugs Program, effective 1 March 2004

We have had recent advice from the Australian Government of changes to the Highly Specialised Drugs Program, effective 1 March 2004.

ADD DRUG

Bosentan monohydrate

CAUTION:
Bosentan monohydrate is a category X drug and must not be given to pregnant women. Pregnancy must be avoided during treatment and for at least 3 months following cessation of treatment with this drug.

NOTE:
Any queries concerning the arrangements to prescribe bosentan monohydrate may be directed to the Health Insurance Commission on 1800 700 270 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday).

Written applications for authority to prescribe bosentan monohydrate should be forwarded to:

Health Insurance Commission
Prior Written Approval of Specialised Drugs
Reply Paid 9826
GPO Box 9826
HOBART TAS 7001

NOTE:
Bosentan monohydrate is not PBS-subsidised for patients with pulmonary hypertension secondary to interstitial lung disease associated with scleroderma, where the total lung capacity is less than 70% of that predicted.

The following provides some explanatory Notes regarding the availability of PBS-subsidised treatment with bosentan monohydrate of primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma, in patients with disease of WHO Functional Class III or IV severity.

1. Definition of primary pulmonary hypertension and pulmonary arterial hypertension secondary to scleroderma.

Primary pulmonary hypertension and pulmonary arterial hypertension secondary to scleroderma are defined as follows:

mean pulmonary artery pressure (mPAP) greater than 25 mmHg at rest and pulmonary capillary wedge pressure (PCWP) less than 18 mmHg; or
mPAP greater than 30 mmHg with exercise and PCWP less than 18 mmHg; or
where a right heart catheter cannot be performed on clinical grounds, right ventricular systolic pressure (RVSP), assessed by echocardiography (ECHO), greater than 40 mmHg, with normal left ventricular function.

2. Definition of WHO Functional Class III or IV disease severity.

WHO Functional Class III disease severity is defined as follows:
Patients with pulmonary hypertension resulting in marked limitation of physical activity who are comfortable at rest and on ordinary physical activity experience dyspnoea or fatigue, chest pain or near syncope.
WHO Functional Class IV disease severity is defined as follows:
Patients with the inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.

3. Designated hospitals.

Refer to HIC website at www.hic.gov.au for a list of designated hospitals.

4. Test requirements to establish baseline for initiation of treatment and response to treatment for continuation of treatment.

(a) Initiation of treatment.
Written applications for PBS-subsidised treatment should be accompanied by the results of a right heart catheter (RHC) composite assessment, plus an ECHO composite assessment, plus a 6 minute walk test (6MWT) to establish the patient's baseline measurements.

Where it is not possible to perform all 3 tests above on clinical grounds, the following list outlines the preferred test combination, in descending order, for the purposes of initiation of PBS-subsidised treatment:

RHC plus ECHO composite assessments;
RHC composite assessment plus 6MWT;
RHC composite assessment only.

In circumstances where a RHC cannot be performed on clinical grounds, applications may be submitted to the HIC for consideration based on the results of the following test combinations, which are listed in descending order of preference:

ECHO composite assessment plus 6MWT;
ECHO composite assessment only.

Where fewer than 3 tests are able to be performed on clinical grounds, a reason outlining why the particular test/s could not be conducted must be provided with the authority application.

For patients who commence bosentan monohydrate therapy on or after 1 March 2004, the test results provided with the application for initial treatment must be no more than 2 months old at the time of application.

For patients with primary pulmonary hypertension and pulmonary arterial hypertension secondary to scleroderma who were commenced on bosentan monohydrate treatment prior to 1 March 2004 and who have received less than 6 months of treatment with bosentan monohydrate at the time of application, the first application for PBS-subsidised treatment must include, where available, all 3 test results at the time that the patient commenced treatment with bosentan monohydrate (baseline).

For patients with primary pulmonary hypertension and pulmonary arterial hypertension secondary to scleroderma who were commenced on bosentan monohydrate treatment prior to 1 March 2004 and who have received 6 or more months of treatment at the time of application, the first application for PBS-subsidised treatment must include, where available, all 3 test results at the time that the patient commenced treatment with bosentan monohydrate (baseline), plus the test results at the time of application. The latter test results must be no more than 2 months old.

(b) Continuation of treatment.
The following list outlines the preferred test combination, in descending order, for the purposes of continuation of PBS-subsidised treatment:

RHC plus ECHO composite assessments plus 6MWT;
RHC plus ECHO composite assessments;
RHC composite assessment plus 6MWT;
ECHO composite assessment plus 6MWT;
RHC composite assessment only;
ECHO composite assessment only.

The results of the same tests as conducted at baseline should be provided with each written continuing treatment application (i.e. every 6 months), except for patients who were able to undergo all 3 tests at baseline, and whose subsequent ECHO and 6MWT results demonstrate disease stability or improvement, in which case RHC can be omitted. In all other patients, where the same test(s) conducted at baseline cannot be performed for assessment of response on clinical grounds, a reason why the test(s) could not be conducted must be provided with the application.

The test(s) results provided with the application for continuing treatment must be no more than 2 months old at the time of application.

5. Definition of response to bosentan monohydrate or prior vasodilator treatment.

For adult patients with 2 or more baseline tests, response to treatment is defined as 2 or more tests demonstrating stability or improvement of disease, as assessed by a physician from a designated hospital.

For adult patients with a RHC composite assessment alone at baseline, response to treatment is defined as a RHC result demonstrating stability or improvement of disease, as assessed by a physician from a designated hospital.

For adult patients with an ECHO composite assessment alone at baseline, response to treatment is defined as an ECHO result demonstrating stability or improvement of disease, as assessed by a physician from a designated hospital.

For patients aged less than 18 years, response to treatment is defined as at least 1 of the baseline tests demonstrating stability or improvement of disease, as assessed by a physician from a designated hospital.

6. Authority approval requirements.

(a) Initiation of PBS-subsidised treatment.
(i) De-novo patients.

For the initial treatment of patients who commence therapy on or after 1 March 2004, 1 written application which includes 2 separate authority prescriptions must be submitted to the HIC for authorisation. The total duration of initial PBS-subsidised treatment that will be approved with this first written application is up to 6 months.

Approvals for the first authority prescription will be limited to 1 month of therapy with the 62.5 mg strength tablet, with the quantity approved based on the dosage recommendations in the Therapeutic Goods Administration (TGA)-approved Product Information. No repeats will be authorised for this prescription. The second authority prescription may be written for either the 62.5 mg tablet or the 125 mg tablet strengths. Where the 62.5 mg tablet strength is required, please contact the HIC on 1800 700 270 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday) for further advice. Approvals for the second authority prescription will be limited to 1 month of treatment, with the quantity approved based on the dosage recommendations in the TGA-approved Product Information, and a maximum of 4 repeats. The approved second authority prescription will be returned to the prescriber by the HIC 2 weeks after the date of the approval of the first authority prescription, to allow for the uninterrupted completion of the 6 month initial treatment course. The HIC will contact prescribers prior to dispatch of the second authority prescription to confirm the tablet strength required for the patient.

(ii) Patients who commenced bosentan monohydrate prior to 1 March 2004.
For patients with primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma who commenced treatment with bosentan monohydrate prior to
1 March 2004 and who have received less than 6 months of treatment at the time of application, a written application, accompanied by 1 authority prescription must be submitted to the HIC for authorisation. Approvals will provide sufficient supply to allow the patient to complete a total of 6 months of combined PBS-subsidised and non-PBS-subsidised treatment, with the quantity approved based on the dosage recommendations in the TGA-approved product information.

For patients with primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma who commenced treatment with bosentan monohydrate prior to
1 March 2004 and who have received 6 or more months of treatment at the time of application, a written application, accompanied by 1 authority prescription must be submitted to the HIC for authorisation. Approvals will be limited to provide sufficient supply of PBS-subsidised treatment to allow the patient to receive 6 months of treatment, with the quantity approved based on the dosage recommendations in the TGA-approved Product Information.

All patients with primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma who commenced treatment with bosentan monohydrate prior to
1 March 2004 will be eligible to commence PBS-subsidised treatment with bosentan monohydrate. Thereafter, to be eligible for further PBS-subsidised supply, patients must demonstrate a response to bosentan monohydrate treatment, as defined above under definition of response.

(b) Continuation of treatment.
Written applications for continuing treatment must be submitted to the HIC for authorisation every 6 months. Approvals will be limited to provide sufficient supply for up to a maximum of 6 months of treatment, based on the dosage recommendations in the TGA-approved Product Information.

Applications for continuing treatment will only be approved for patients who have demonstrated a response to bosentan monohydrate treatment. The assessment of the patient's response to the initial and subsequent 6 month courses of treatment should be made following the preceding 5 months of treatment, in order to allow sufficient time for a response to be demonstrated. Applications for continuing treatment with bosentan monohydrate should be made prior to the completion of the 6 month treatment course to ensure continuity for those patients who respond to treatment, as assessed by the treating physician.

(c) Cessation of treatment.
For patients ceasing treatment, approval will only be granted to provide sufficient supply of the 62.5 mg tablet strength to allow gradual dose reduction over a period of no more than 1 month duration. Prescribers should telephone the HIC on 1800 700 270 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday) to receive authorisation for this final supply and to ensure no unintended break in treatment occurs.

7. Re-treatment with bosentan monohydrate.

Patients who do not respond to treatment are not eligible to receive further PBS-subsidised treatment with bosentan monohydrate under any circumstances.

8. Further information.

A diagrammatical representation of the above information and the restriction can be obtained from the HIC website at www.hic.gov.au.

Public hospital authority required

Initial treatment of adult patients who have been assessed by a physician from a designated hospital to have:

(a) WHO Functional Class III primary pulmonary hypertension and a mean right atrial pressure of 8 mmHg or less, as measured by RHC, unless a RHC is contraindicated on clinical grounds;

(b) WHO Functional Class III pulmonary arterial hypertension secondary to scleroderma and a mean right atrial pressure of 8 mmHg or less, as measured by RHC, unless a RHC is contraindicated on clinical grounds.

Patients must have failed to respond [see Note for definition of response] to 6 or more weeks of appropriate vasodilator treatment unless intolerance or a contraindication to such treatment exists.

In circumstances where a RHC cannot be performed on clinical grounds, applications may be submitted to the HIC for consideration based on the test results of the ECHO composite assessment plus 6MWT or the ECHO composite assessment only.

Applications for authorisation must be in writing and must include:

(1) two completed authority prescription forms [see Note for authority approval requirements]; and

(2) a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results from the 3 tests below, where available:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; and

(3) a copy of a signed patient acknowledgment form indicating that the patient understands and acknowledges that PBS-subsidised treatment with bosentan monohydrate for primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma will cease if the treating physician determines that the patient has not achieved a response to treatment [see Note for definition of response].

Details of prior vasodilator treatment, including the dose and duration of treatment, must be provided at the time of application. Where the patient is commenced on bosentan monohydrate treatment due to an adverse event or a contraindication to vasodilator treatment, details on the nature of the adverse event or contraindication according to the TGA-approved Product Information must also be provided with the application.

Where fewer than 3 tests (see requirement 2 above) are able to be performed on clinical grounds, a reason outlining why the particular test/s could not be conducted must be provided with the authority application [see Note for test requirements].

The maximum quantity authorised will be limited to provide sufficient supply for 1 month of treatment, based on the dosage recommendations in the TGA-approved Product Information. No repeats will be authorised for the first authority prescription issued under this criterion [see Note for full details of authority approval requirements]. A maximum of 4 repeats will be authorised for the second authority prescription issued under this criterion. Where fewer than 4 repeats are initially requested with the second authority prescription, authority approvals for sufficient repeats to complete a maximum of 6 months of treatment may be requested by telephone.

Public hospital authority required

Initial treatment of adult patients who have been assessed by a physician from a designated hospital to have:
(a) WHO Functional Class III primary pulmonary hypertension and a mean right atrial pressure greater than 8 mmHg, as measured by RHC, unless a RHC is contraindicated on clinical grounds;
OR
(b) WHO Functional Class III pulmonary arterial hypertension secondary to scleroderma and a mean right atrial pressure greater than 8 mmHg, as measured by RHC, unless a RHC is contraindicated on clinical grounds;
OR
(c) WHO Functional Class IV primary pulmonary hypertension;
OR
(d) WHO Functional Class IV pulmonary arterial hypertension secondary to scleroderma.

Applications for authorisation must be in writing and must include:
(1) two completed authority prescription forms (see NOTE for authority approval requirements); and
(2) a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results from the 3 tests below, where available:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; and

Public hospital authority required

Initial treatment of patients aged less than 18 years who have been assessed by a physician from a designated hospital and who have WHO Functional Class III primary pulmonary hypertension and either a mean right atrial pressure of 8 mmHg or less, as measured by RHC, or, where a RHC cannot be performed on clinical grounds, normal right ventricular function as assessed by ECHO.

Patients must have failed to respond [see Note for definition of response] to 6 or more weeks of appropriate prior vasodilator treatment unless intolerance or a contraindication to such treatment exists.

Applications for authorisation must be in writing and must include:

(1) two completed authority prescription forms [see Note for authority approval requirements]; and
(2) a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results from the 3 tests below, where available:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; and

(3) a copy of a patient acknowledgment form, signed by the parent or authorised guardian, indicating that they understand and acknowledge that PBS-subsidised treatment with bosentan monohydrate for primary pulmonary hypertension will cease if the treating physician determines that the patient has not achieved a response to treatment [see Note for definition of response].

Details of prior vasodilator treatment, including the dose and duration of treatment must be provided at the time of application. Where the patient is commenced on bosentan monohydrate treatment due to an adverse event or a contraindication to vasodilator treatment, details on the nature of the adverse event or contraindication according to the TGA-approved Product Information must also be provided with the application.

Public hospital authority required

Initial treatment of patients aged less than 18 years who have been assessed by a physician from a designated hospital to have:

(a) WHO Functional Class III primary pulmonary hypertension and either a mean right atrial pressure greater than 8 mmHg, as measured by RHC, or, where a RHC cannot be performed on clinical grounds, right ventricular dysfunction as assessed by ECHO;
OR
(b) WHO Functional Class IV primary pulmonary hypertension.

Applications for authorisation must be in writing and must include:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; and

Public hospital authority required

Initial PBS-subsidised supply for continuing treatment of patients who have been assessed by a physician from a designated hospital to have WHO Functional Class III or IV primary pulmonary hypertension, or WHO Functional Class III or IV pulmonary arterial hypertension secondary to scleroderma, and who were receiving treatment with bosentan monohydrate prior to 1 March 2004.

Applications for authorisation must be in writing and must include:

(1) a completed authority prescription form [see Note on authority approval requirements]; and
(2) (a) for patients who have received less than 6 months of bosentan monohydrate treatment at the time of application - a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results of the following 3 tests, where available, at the time treatment with bosentan monohydrate was commenced:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; or

(b) for patients who have received 6 or more months of bosentan monohydrate treatment at the time of application - a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results of the following 3 tests, both at the time treatment with bosentan monohydrate was commenced and at the time of application, where available:

RHC composite assessment; and
ECHO composite assessment; and
6MWT; and

(3) the date of commencement of bosentan monohydrate treatment; and
(4) (a) for adult patients - a copy of a signed patient acknowledgment form indicating that the patient understands and acknowledges that PBS-subsidised treatment with bosentan monohydrate for primary pulmonary hypertension or pulmonary arterial hypertension secondary to scleroderma will cease if the treating physician determines that the patient has not achieved a response to treatment [see Note for definition of response]; or
(b) for patients aged less than 18 years - a copy of a patient acknowledgment form, signed by the parent or authorised guardian, indicating that they understand and acknowledge that PBS-subsidised treatment with bosentan monohydrate for primary pulmonary hypertension will cease if the treating physician determines that the patient has not achieved a response to treatment [see Note for definition of response].

Where fewer than 3 tests (see requirement 2a or 2b above) are able to be performed on clinical grounds, a reason outlining why the particular test/s could not be conducted must be provided with the authority application [see Note for test requirements].

The maximum quantity authorised will be limited to provide sufficient supply for 1 month of treatment, based on the dosage recommendations in the TGA-approved Product Information. The number of repeats authorised will be dependent on the duration of prior bosentan monohydrate therapy. Where patients have received less than 6 months of non-PBS-subsidised treatment with bosentan monohydrate , sufficient repeats to allow the patient to complete a total of 6 months of combined PBS-subsidised and non-PBS-subsidised therapy will be authorised. Where patients have received 6 months or more of non-PBS-subsidised treatment with bosentan monohydrate, up to 5 repeats will be authorised.

Where fewer than the number of repeats to allow the patient to complete a total of 6 months of non-PBS-subsidised and/or PBS-subsidised bosentan monohydrate therapy are initially requested under this criterion, authority approvals for sufficient repeats to complete a total of 6 months of non-PBS-subsidised and PBS-subsidised treatment may be requested by telephone.

Public hospital authority required

Continuing PBS-subsidised treatment of patients with WHO Functional Class III or IV primary pulmonary hypertension or WHO Functional Class III or IV pulmonary arterial hypertension secondary to scleroderma, who have received approval for initial PBS-subsidised treatment with bosentan monohydrate and have completed the initial treatment course, and who have been assessed by a physician from a designated hospital to have achieved a response to treatment [see Note for definition of response].

Applications for authorisation must be in writing and must include:

(1) a completed authority prescription form; and
(2) a completed Bosentan Monohydrate (Tracleer) PBS Authority Application - Supporting Information form [may be downloaded from the HIC website (www.hic.gov.au)] which includes results from the 3 tests below, where available:

RHC composite assessment; and
ECHO composite assessment; and
6MWT.

Where fewer than 5 repeats are initially requested under this criterion, authority approvals for sufficient repeats to complete a maximum of 6 months of treatment may be requested by telephone.

Public hospital authority required

Final PBS-subsidised supply for patients with WHO Functional Class III or IV primary pulmonary hypertension or WHO Functional Class III or IV pulmonary arterial hypertension secondary to scleroderma who have not responded to bosentan monohydrate therapy [see Note for definition of response], to allow for gradual cessation of treatment.

Applications for authorisation under this criterion should be made on the telephone [see Note on authority approval requirements].

Approval will only be granted for the 62.5 mg tablet strength. The maximum quantity authorised will be limited to provide sufficient supply for 1 month of treatment.

Under no circumstances will telephone approvals be granted for treatment that would extend the final treatment period beyond 1 month.

6429J	Tablet 62.5 mg (base)	60	$4,035.00	Tracleer	AT
6430K	Tablet 125 mg (base)	60	$4,035.00	Tracleer	AT

NOTE:
These prices are based on special supply arrangements-see Pharmaceutical Benefits Pricing Authority relativity sheet for full details.

Changes notified by hospital circular will be updated in the Guidelines on the Commonwealth/State Highly Specialised Drugs Program Guidelines website and the claim form amended.

Noreen Dowd
Director, Programs
Metropolitan Health & Aged Care Services