Decision to widen access to various anti-infectives

Medicines Decision

What we’re doing

We’re pleased to announce our decision to widen funded access to three treatments:

  • Ledipasvir with sofosbuvir
  • Tenofovir disoproxil fumarate
  • Paromomycin

All changes will take effect from 1 January 2018.

Any changes to the original proposal?

This was the subject of a consultation letter dated 14 November 2017.   The final decision differs from the original proposal in the following way:

  • Ledipasvir with sofosbuvir: the funding requirement for patients with mixed cryoglobulinaemia with an associated purpuric skin rash to have cryoglobulinaemic glomerulonephritis has been amended to remove the cryoglobulins requirement for glomerulonephritis.
  • Tenofovir: separate to the issue of women of childbearing potential, the current funding criteria for tenofovir for severe hepatitis B required a “Mayo score” greater than 20. We were advised that Mayo scores are not used in practice anymore, so we have removed this requirement entirely.
  • Tenofovir: earlier this year, PHARMAC had widened funded access to HIV treatments to remove severity requirements. This was done to tenofovir in Section B but not in Section H. This was an oversight, and as part of this decision this has been corrected.
  • Tenofovir: During updating the restrictions we identified a number of typos in the current criteria. These have been fixed.
  • Paromomycin: We have amended the criteria so that gastroenterologists may apply for funded paromomycin. This change was made both in Section B and Section H. 

Who we think will be most interested

Among other groups, this decision will be of interest to:

  • community and hospital prescribers, particularly Infectious Disease specialists and general practitioners,
  • hospital and community pharmacists, DHBs, suppliers and wholesalers, and
  • patients with hepatitis B or C and consumer advocacy groups.

What will the effect of our decision be?

From 1 January 2018

Ledipasvir with sofosbuvir: Patients with chronic hepatitis C and decompensated cirrhosis will no longer need to meet a minimum MELD score (a measure of severity) to be eligible for funded treatment.

Tenofovir disoproxil fumarate: Women of childbearing age with hepatitis B will be eligible for funded tenofovir. Tenofovir provides the same benefit against the virus as other funded treatments such as entecavir, but has a lower risk of causing harm to an unborn child.

Paromomycin: will be funded for eradication of Entamoeba histolytica carriage. 

Detail about this decision

Ledipasvir with sofosbuvir (Harvoni)

From 1 January 2018, the Special Authority criteria for ledipasvir with sofosbuvir (Harvoni) tab 90 mg with sofosbuvir 400 mg will be amended as follows (additions in bold, deletions in strikethrough):

Special Authority for Subsidy

Chronic hepatitis C – Advanced disease - ribavirin is not contraindicated

Applications from any relevant practitioner. Approvals valid for 12 weeks for applications meeting the following criteria:

All of the following:

1 Patient has chronic hepatitis C (any genotype); and

2 Ribavirin treatment is not contraindicated; and

3 Any of the following:

3.1     Patient has decompensated cirrhosis (Child-Pugh B or C) with a MELD score of 12 or greater; or
3.2     Patient has been accepted onto a list for a liver transplant or has received a liver transplant; or
3.3     Patient has essential mixed cryoglobulinaemia with associated purpuric skin rash and; either

3.3.1       Cryoglobulinaemic gGlomerulonephritis; or
3.3.2       Systemic vasculitis.

Chronic hepatitis C – Advanced disease - ribavirin is contraindicated

Applications from any relevant practitioner. Approvals valid for 24 weeks for applications meeting the following criteria:

All of the following:

1 Patient has chronic hepatitis C (any genotype); and

2 Ribavirin treatment is contraindicated; and

3 Any of the following:

3.1     Patient has decompensated cirrhosis (Child-Pugh B or C) with a MELD score of 12 or greater; or
3.2     Patient has been accepted onto a list for a liver transplant or has received a liver transplant; or
3.3     Patient has essential mixed cryoglobulinaemia with associated purpuric skin rash and; either:

3.3.1       Cryoglobulinaemic gGlomerulonephritis; or
3.3.2       Systemic vasculitis.

Tenofovir disoproxil fumarate (Viread)

From 1 January 2018, the Special Authority criteria for tenofovir disoproxil fumarate (Viread) tab 300 mg will be amended as follows (additions in bold, deletions in strikethrough):

TENOFOVIR DISOPROXIL FUMARATE – Subsidy by endorsement; can be waived by Special Authority see SA1362QQQQ

Endorsement for treatment of HIV: Prescription is deemed to be endorsed if tenofovir disoproxil fumarate is co-prescribed with another anti-retroviral antiretroviral subsidised under Special Authority SA1651 and the prescription is annotated accordingly by the Pharmacist or endorsed by the prescriber.

Note:

Tenofovir disoproxil fumarate prescribed under endorsement for the treatment of HIV is included in the count of up to 4 subsidised antiretrovirals for the purposes of Special Authority SA1651

Tab 300 mg ..............................................................531.00              30                      ✔ Viread

➽SA1362QQQQ Special Authority for Waiver of Rule

Initial application — (Chronic Hepatitis B) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid without further renewal unless notified for applications meeting the following criteria:

Any of the following: Both:

1 All of the following:

1.1     Patient has confirmed Hepatitis B infection (HBsAg positive for more than 6 months); and
1.2     Patient has had previous lamivudine, adefovir or entecavir therapy; and
1.3     HBV DNA greater than 20,000 IU/mL or increased 10 fold or higher over nadir; and
1.4     Any of the following:

1.4.1       Lamivudine resistance - detection of M204I/V mutation; or
1.4.2       Adefovir resistance - detection of A181T/V or N236T mutation; or
1.4.3       Entecavir resistance - detection of relevant mutations including I169T, L180M T184S/A/I/L/G/C/M, S202C/G/I, M204V or M250I/V mutation; or

2 Patient is either listed or has undergone liver transplantation for HBV; or

3 Patient has decompensated cirrhosis with a Mayoscore > 20.

Initial application — (Pregnant, Women of child bearing age with active hepatitis B) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid for 12 months 2 years for applications meeting the following criteria:

Both: All of the following:

1 Patient is HBsAg positive and pregnant; and

2 Either:

2.1     HBV DNA > 20,000 IU/mL and ALT > ULN; or
2.2     HBV DNA > 20 million IU/mL and ALT normal; and

3 Either:

3.1     Patient is of child bearing potential and has not yet completed a family; or
3.2     Patient is pregnant; or
3.3     Patient is breastfeeding.

Renewal — (Confirmed Hepatitis B following funded tenofovir treatment for pregnancy within the previous two years) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid without further renewal unless notified for applications meeting the following criteria:

Either:

1 All of the following:

1.1     Patient has confirmed Hepatitis B infection (HBsAg positive for more than 6 months); and
1.2     Patient has had previous lamivudine, adefovir or entecavir therapy; and
1.3     HBV DNA greater than 20,000 IU/mL or increased 10 fold or higher over nadir; and
1.4     Any of the following:

1.4.1      Lamivudine resistance - detection of M204I/V mutation; or
1.4.2      Adefovir resistance - detection of A181T/V or N236T mutation; or
1.4.3      Entecavir resistance - detection of relevant mutations including I169T, L180M T184S/A/I/L/G/C/M, S202C/G/I, M204V or M250I/V mutation; or

2 Patient is either listed or has undergone liver transplantation for HBV.

Renewal — (Subsequent pregnancy or Breastfeeding, Women of child bearing age with active hepatitis B) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid for 12 months 2 years for applications meeting the following criteria:

Both: All of the following:

1 Patient is HBsAg positive and pregnant or breastfeeding; and

2 Either:

2.1     HBV DNA > 20,000 IU/mL and ALT > ULN; or
2.2     HBV DNA > 20 million IU/mL and ALT normal; and

3 Any of the following:

3.1     Patient is of child bearing potential and has not yet completed a family; or
3.2     Patient is pregnant; or
3.3     Patient is breastfeeding.

Initial application — (Pregnant, prevention of vertical transmission) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid for 6 months for applications meeting the following criteria:

Both:

1 Patient is HBsAg positive and pregnant; and

2 HBV DNA > 20 million IU/mL and ALT normal.

Renewal — (Subsequent pregnancy, prevention of vertical transmission) only from a gastroenterologist, infectious disease specialist or general physician. Approvals valid for 6 months for applications meeting the following criteria:

Both:

1 Patient is HBsAg positive and pregnant; and

2 HBV DNA > 20 million IU/mL and ALT normal.

Notes:
  • Tenofovir disoproxil fumarate should be stopped 6 months following HBeAg seroconversion for patients who were HBeAg positive prior to commencing this agent and 6 months following HBsAg seroconversion for patients who were HBeAg negative prior to commencing this agent.
  • The recommended dose of Tenofovir disoproxil fumarate for the treatment of all three indications is 300 mg once daily.
  • In patients with renal insufficiency (calculated creatinine clearance less than 50ml/min), Tenofovir disoproxil fumarate dose should be reduced in accordance with the approved Medsafe datasheet guidelines.
  • Tenofovir disoproxil fumarate is not approved for use in children.

Also from 1 January 2018, the hospital restrictions for tenofovir disoproxil fumarate (Viread) tab 300 mg will be amended as follows (additions in bold, deletions in strikethrough):

➥ Restricted

Initiation – Confirmed hepatitis B

Any of the following: Both:

1 All of the following:

1.1     Patient has confirmed Hepatitis B infection (HBsAg positive for more than 6 months); and
1.2     Patient has had previous lamivudine, adefovir or entecavir therapy; and
1.3     HBV DNA greater than 20,000 IU/mL or increased less than or equal to 10-fold 10 fold or higher over nadir; and
1.4     Any of the following:

1.4.1      Lamivudine resistance - detection of M204I/V mutation; or
1.4.2      Adefovir resistance - detection of A181T/V or N236T mutation; or
1.4.3      Entecavir resistance - detection of relevant mutations including I169T, L180M T184S/A/I/L/G/C/M, S202C/G/I,M204V S202C/G/I, M204V or M250I/V mutation; or

2 Patient is either listed or has undergone liver transplantation for HBV; or

3 Patient has a decompensated cirrhosis with a Mayo score less than or equal togt; 20.

Initiation –Pregnant or Breastfeeding, Women of child bearing age with active Active hepatitis B

Limited to 12 months treatment

Both: All of the following:

1 Patient is HBsAg positive and pregnant; and

2 Either:

2.1     HBV DNA > less than or equal togt; 20,000 IU/mL and ALT > less than or equal togt; ULN.; or
2.2     HBV DNA > 20 million IU/mL and ALT normal; and

3 Any of the following:

3.1     Patient is of child bearing potential and has not yet completed a family; or
3.2     Patient is pregnant; or
3.3     Patient is breastfeeding.

Initiation – Pregnant, prevention of vertical transmission

Limited to 6 months treatment

Both:

1 Patient is HBsAg positive and pregnant; and

2 HBV DNA less than or equal togt; 20 million IU/mL and ALT normal.

Initiation – Confirmed HIV

Both: Patient has

1 Cconfirmed HIV infection.; and

2 Any of the following:

2.1     Symptomatic patient; or
2.2     Patient aged 12 months and under; or
2.3     Both:

2.3.1      Patient aged 1 to 5 years; and
2.3.2      Any of the following:

2.3.2.1    CD4 counts less than or equal tolt; 1000 cells/mmless than or equal to#xB3;; or
2.3.2.2    CD4 counts less than or equal tolt; 0.25 less than or equal to#xD7; total lymphocyte count; or
2.3.2.3    Viral load counts less than or equal togt; 100000 copies per ml; or

2.4     Both:

2.4.1      Patient aged 6 years and over; and
2.4.2      CD4 counts less than or equal tolt; 500 cells/mmless than or equal to#xB3;.

Initiation – Prevention of maternal transmission

Either:

1 Prevention of maternal foetal transmission; or

2 Treatment of the newborn for up to eight weeks.

Initiation – Post-exposure prophylaxis following non-occupational exposure to HIV

Both:

1 Treatment course to be initiated within 72 hours post exposure; and

2 Any of the following:

2.1     Patient has had unprotected receptive anal intercourse with a known HIV positive person; or
2.2     Patient has shared intravenous injecting equipment with a known HIV positive person; or
2.3     Patient has had non-consensual intercourse and the clinician considers that the risk assessment indicates prophylaxis is required.

Initiation – Percutaneous exposure

Patient has percutaneous exposure to blood known to be HIV positive.

Paromomycin (Humatin)

From 1 January 2018, the Special Authority criteria for paromomycin (Humatin) cap 250 mg will be amended as follows (additions in bold, deletions in strikethrough):

Special Authority for Subsidy

Initial application only from an infectious disease specialist, or clinical microbiologist, or gastroenterologist. Approvals valid for 1 month for applications meeting the following criteria:

Either:

1 where the pPatient has confirmed cryptosporidium infection; or

2 For the eradication of Entamoeba histolytica carriage.

Renewal only from an infectious disease specialist, or clinical microbiologist or gastroenterologist. Approvals valid for 1 month for applications meeting the following criteria:

Either:

1 where the pPatient has confirmed cryptosporidium infection; or

2 For the eradication of Entamoeba histolytica carriage.

Also from 1 January 2018, the hospital restrictions for paromomycin (Humatin) cap 250 mg will be amended as follows (additions in bold, deletions in strikethrough):

Restricted

Clinical microbiologist, or infectious disease specialist or gastroenterologist.

Our response to what you told us

We appreciate all the feedback we received and are grateful for the time people took to respond to this consultation. All consultation responses received by 28 November 2017 were considered in their entirety when making the decision. The table below summarises the main themes raised in feedback.

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz or call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 66 00 50.

Feedback theme

PHARMAC response

Supported funding of treatments for other hepatitis C patients, such as funding a pangenotypic agent.

PHARMAC is assessing funding applications for a number of hepatitis C treatments for various patient groups.

Remove cryoglobulins as a criterion for patients with glomerulonephritis who will require a kidney transplant without hep C treatment.

We have made this change.

A note should be added to ledipasvir with sofosbuvir stating that for patients with genotype 3, 12 weeks with ribavirin results in a higher SVR rate than 24 weeks without ribavirin.

The rules for funding of Harvoni require a patient to have a 12 week maximum course if ribavirin if not contraindicated. Patients who can take ribavirin are not eligible for a funded 24 week course whether with or without ribavirin.

The distribution arrangement for Viekira Pak is preferred to the Harvoni model and should be a model for other XPharm medicines.

Noted.

Access to tenofovir should be widened such that patients with undetectable HBV DNA and ALT normal can access it if they were on entecavir.

PHARMAC recently conducted an RFP for hepatitis B agents, which included seeking pricing for widening of funded access, and is currently evaluating bids.

Tenofovir should be funded as an original pack or have the wastage rule applied, as should any medicine with a list price over $150.

This is an ongoing treatment, in packs of 30, for which patients would receive long term treatment, so we consider wastage is unlikely.

Applications for paromomycin should be able to come from gastroenterologists.

We have adding gastroenterologists to the possible applicants for paromomycin.

Should a registered product for paromomycin become available, the wastage rule be applied.

Should a registered paromomycin product become available, we would consider pharmacy reimbursement claiming rules at that time.