Proposal for various medicines in the neurology, immunology and nephrology therapeutic areas approved

Medicines

Decision

PHARMAC is pleased to announce the approval of a proposal relating to certain medicines in the neurology, immunology and nephrology therapeutic areas to take effect from 1 July 2017.

This was the subject of a consultation letter dated 21 April 2017.

In summary, the effect of the decision is that:

  • Midazolam injection (Pfizer) will be available on a Practitioners Supply Order for use in status epilepticus
  • Infliximab (Remicade) hospital restrictions will be widened to include treatment of neurosarcoidosis and Behçet’s disease, and the ocular inflammation criteria will be amended.
  • Enoxaparin (Clexane) access will be widened to include use during home haemodialysis.

Changes to the Decision following Consultation Feedback

  • The approved hospital restrictions for infliximab for ocular inflammation differ slightly from those consulted on; however, the intent remains unchanged. Minor formatting changes were required for administrative reasons.  
  • The quantities of midazolam ampoules available on a PSO were increased such that up to 10 x midazolam 1 mg per ml, 5 ml plastic ampoules and up to 5 x 5 mg per ml, 3 ml plastic ampoules will be available.  This will improve pharmacy dispensing efficiency and potential wastage as outlined in the responses to feedback below.

Details of the decision

Midazolam injection – add to PSO for use in status epilepticus

  • Midazolam (Pfizer) injection 1 mg per ml, 5 ml and 5 mg per ml, 3 ml plastic ampoules will become available on a Practitioners Supply Order for use in status epilepticus in Section B of the Pharmaceutical Schedule from 1 July 2017 as follows:

MIDAZOLAM – Safety medicine; prescriber may determine dispensing frequency

Inj 1 mg per ml, 5 ml plastic ampoule – up to 10 inj available on a PSO.

PSO for status epilepticus use only. PSO must be endorsed for status epilepticus use only.

Inj 5 mg per ml, 3 ml plastic ampoule – up to 5 inj available on a PSO.

PSO for status epilepticus use only. PSO must be endorsed for status epilepticus use only.

Infliximab – widen access for neurosarcoidosis and Behçet’s disease

  • Restrictions on the use of infliximab injection 100 mg (Remicade) in DHB hospitals will be widened to include the treatment of neurosarcoidosis and Behçet’s disease via the addition of the following hospital restrictions in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 as follows:

Restricted

Initiation – neurosarcoidosis

Neurologist

Re-assessment required after 18 months

All of the following:

  1. Biopsy consistent with diagnosis of neurosarcoidosis; and
  2. Patient has CNS involvement; and
  3. Patient has steroid-refractory disease; and
  4. Either:

4.1   IV cyclophosphamide has been tried; or
4.2   Treatment with IV cyclophosphamide is clinically inappropriate.

Continuation – neurosarcoidosis

Neurologist

Re-assessment required after 18 months

Either:

  1. A withdrawal period has been tried and the patient has relapsed; or
  2. All of the following:

2.1   A withdrawal period has been considered but would not be clinically appropriate; and
2.2   There has been a marked reduction in prednisone dose; and
2.3   Either:

2.3.1 There has been an improvement in MRI appearances; or
2.3.2 Marked improvement in other symptomology.

Initiation – severe Behcet's disease

Re-assessment required after 4 months

All of the following:

1. The patient has severe Behcet's disease which is significantly impacting the patient’s quality of life (see Notes); and

2. Either:

2.1   The patient has severe ocular, neurological and/or vasculitic symptoms and has not responded adequately to one or more treatment(s) appropriate for the particular symptom(s) (see Notes); or
2.2   The patient has severe gastrointestinal, rheumatologic and/or mucocutaneous symptoms and has not responded adequately to two or more treatment appropriate for the particular symptom(s) (see Notes); and

3. The patient is experiencing significant loss of quality of life.

Notes.

  1. Behcet’s disease diagnosed according to the International Study Group for Behcet’s Disease. Lancet 1990;335(8697):1078-80. Quality of life measured using an appropriate quality of life scale such as that published in Gilworth et al J Rheumatol. 2004;31:931-7.
  2. Treatments appropriate for the particular symptoms are those that are considered standard conventional treatments for these symptoms, for example intravenous/oral steroids and other immunosuppressants for ocular symptoms; azathioprine, steroids, thalidomide, interferon alpha and ciclosporin for mucocutaneous symptoms; and colchicine, steroids and methotrexate for rheumatological symptoms.

Continuation – Severe Behcet's disease

Re-assessment required after 6 months

Both:

  1. Patient has had a good clinical response to initial treatment with measurably improved quality of life; and
  2. Infliximab to be administered at doses no greater than 5 mg/kg every 8 weeks.
  • Restrictions on use of infliximab injection 100 mg (Remicade) in DHB hospitals would be amended for the indications of ocular inflammation in Part II of Section H of the Pharmaceutical Schedule from 1 July 2017 as follows (additions in bold, deletions in strikethrough) (only affected criteria shown):

Initiation - severe ocular inflammation

Therapy limited to Re-assessment required after 3 doses

Both:

  1. Patient has severe, vision-threatening ocular inflammation requiring rapid control; and
  2. Either:

2.1     Patient has failed to achieve control of severe vision-threatening ocular inflammation following Treatment with high-dose steroids (intravenous methylprednisolone) followed by high dose oral steroids has proven ineffective at controlling symptoms; or
2.2     Patient developed new inflammatory symptoms while receiving high dose steroids.

Initiation - chronic ocular inflammation

Therapy limited to Re-assessment required after 3 doses

Both:

  1. Patient has severe uveitis uncontrolled with treatment of steroids and other immunosuppressants with a severe risk of vision loss; and
  2. Either:

2.1   Patient is 18 years or older and treatment with has tried at least two other immunomodulatory agents has proven ineffective; or
2.2   Patient is under 18 years and treatment with methotrexate has proven ineffective.

Continuation - severe ocular inflammation

Re-assessment required after 12 months

Both:

  1. Patient has had a good clinical response to initial treatment; and
  2. Either:

2.1     A trial withdrawal of infliximab has been trialled and patient has relapsed after trial withdrawal; or
2.2     Patient has Behcet’s disease

Any of the following:

  1. The patient has had a good clinical response following 3 initial doses; or
  2. The patient has had a sustained reduction in inflammation (Standardisation of Uveitis Nomenclature (SUN) criteria < ½+ anterior chamber or vitreous cells, absence of active vitreous or retinal lesions, or resolution of uveitic cystoid macular oedema), following 12 months’ treatment; or
  3. The patient has a sustained steroid sparing effect, allowing reduction in prednisone to <10mg daily, or steroid drops less than twice daily if under 18 years old, following 12 months’ treatment.

Note: A trial withdrawal should be considered after every 24 months of stability, unless the patient is deemed to have extremely high risk of irreversible vision loss if infliximab is withdrawn.

Continuation- chronic ocular inflammation

Re-assessment required after 12 months

Any of the following:

  1. The patient has had a good clinical response following 3 initial doses; or
  2. The patient has had a sustained reduction in inflammation (Standardisation of Uveitis Nomenclature (SUN) criteria < ½+ anterior chamber or vitreous cells, absence of active vitreous or retinal lesions, or resolution of uveitic cystoid macular oedema), following 12 months’ treatment; or
  3. The patient has a sustained steroid sparing effect, allowing reduction in prednisone to <10mg daily, or steroid drops less than twice daily if under 18 years old, following 12 months’ treatment.

Note: A trial withdrawal should be considered after every 24 months of stability, unless the patient is deemed to have extremely high risk of irreversible vision loss if infliximab is withdrawn.

Enoxaparin sodium – widen access to include use in home haemodialysis

  • Access to enoxaparin sodium injections (Clexane) will be widened in Section B of the Pharmaceutical Schedule to include use in haemodialysis from 1 July 2017 as follows (additions in bold, deletions in strikethrough) (only the affected criteria are shown):

Special Authority for Subsidy

Initial application – (Pregnancy, or Malignancy or Haemodialysis) from any relevant practitioner. Approvals valid for 1 year for applications meeting the following criteria:

Either Any of the following:

  1. Low molecular weight heparin treatment is required during a patient’s pregnancy; or
  2. For the treatment of venous thromboembolism where the patient has a malignancy; or
  3. For the prevention of thrombus formation in the extra-corporeal circulation during home haemodialysis.

Renewal – (Pregnancy, or Malignancy or Haemodialysis) from any relevant practitioner. Approvals valid for 1 year for applications meeting the following criteria:

Either Any of the following:

  1. Low molecular weight heparin treatment is required during a patient's pregnancy; or
  2. For the treatment of venous thromboembolism where the patient has a malignancy; or
  3. For the prevention of thrombus formation in the extra-corporeal circulation during home haemodialysis.

Feedback received

We appreciate all the feedback we received and acknowledge the time people took to respond. All consultation responses received by Friday 12 May 2017 were considered in their entirety in making a decision on the proposed changes. Most responses were supportive of the proposal, and the following issues were raised in relation to specific aspects of the proposal:

Theme

Comment

Midazolam injection – addition to PSO for use in status epilepticus

Support midazolam injection (Pfizer) being available on a PSO for use in status epilepticus; will provide timely access to midazolam in the event of a seizure in a medical facility.

Noted

At any one pharmacy, the dispensing volume of midazolam injections is low, therefore request the quantity of midazolam injection available on a PSO is reflective of an original pack size as this would be more efficient for pharmacies and reduce wastage

The proposed quantities available on a PSO have been amended following consideration of this feedback.

Palliative care patients often receive subcutaneous administration of midazolam. It is also used for emergencies/crises in palliative care. Consideration could be given to expanding the indications to include these.

Subcutaneous use of midazolam in the palliative care setting in the emergency setting was out of scope of the proposal. We would welcome a funding application for use in this setting particularly if there is an unmet clinical need. We would then seek clinical advice accordingly.

Information provided on Epistasis (midazolam maleate oromucsal solution in a prefilled syringe). This is registered and available in the UK. Currently under evaluation by the TGA in Australia

We note that Epistasis is not currently registered in NZ. Should the product become registered we would welcome a funding application.

Infliximab – widened access to neurosarcoidosis

Supportive of widening access and proposed criteria. Consider new cases likely to be less than 1-2 per year and definitely not more. Cases are rare and currently require more onerous NPPA process

Noted.

Infliximab – widened access for Behçet’s disease

There would be 1-2 patients per year who would access infliximab with the proposed criteria resulting in minimal impact on our Medical Day Unit.

Noted.

Has had some patients with very good response to infliximab but difficult stretching from 6 weeks to 8 weeks. Concerned about the continuation criteria restricting administration to 8 weekly.

Clinical advice from PTAC recommended that infliximab dosing for Behçet's disease would be 5mg/kg every 8 weeks and this would be the same regardless of which symptoms of Behçet's it was being used for. PHARMAC staff note this dosing restriction also applies to other infliximab indications.

 

Already treat patients with Behcets disease with infliximab under the ocular inflammation criteria but considers having two pathways would be useful.

Noted. PHARMAC staff note that patients with severe acute ocular inflammation secondary Behçet's could initiate treatment under the ophthalmology criteria if needed.

Would dermatologists be able to prescribe infliximab for Behçet's disease.

There are no prescriber restrictions therefore dermatologists (and other hospital clinicians) will be able to prescribe infliximab for Behçet's disease provided the criteria are met.

Infliximab – amendments to ocular inflammation criteria

Feels that reassessment after 3 doses is too short a time frame to be sure of response. Six months (such as with the Behcets criteria) would be more appropriate, or 4 months at the shortest. After 3 doses patients have only completed loading doses of infliximab.

The proposed criteria were developed by the Ophthalmology Subcommittee. We note that a good clinical response can be interpreted as either an improvement or non-deterioration of the patient’s symptoms after 3 doses have been given.

 

Enoxaparin sodium – widened access for use in home haemodialysis

Supportive of proposal. Heparin is currently used but consider enoxaparin to be just as good and seemingly no more expensive.

 

This aligns with our analysis.

 

Support enoxaparin access being widened to include use during home haemodialysis. This will ensure those people receiving haemodialysis in a community setting have access to a medicine that is easy to administer to prevent thrombus formation.

Noted.

 

This would result in simplified training (time saving) and less risk of adverse events. There would be cost savings due to fewer consumables required with enoxaparin compared with heparin.

 

Noted.

 

Uncertainty about switching to enoxaparin as heparin infusions are easy to learn but consider it would be good to have the choice.

 

Noted.

 

Note that nationally there are 1500 patients in the dialysis population.

This decision will enable enoxaparin to be available to potentially up to 500 home haemodialysis patients via retail pharmacy. The remaining hospital-based haemodialysis patients can currently access enoxaparin sodium via the Hospital Medicines List (HML), where it is listed unrestricted.

In the majority of community pharmacies, the dispensing volumes of enoxaparin are generally low and intermittent and spreads across multiple strengths. For these reasons the original pack or wastage rule should be applied to all dispensing and strengths of enoxaparin sodium.

Given this amended access will likely represent a very small proportion of the total community enoxaparin sodium usage, we do not consider the application of the wastage rule is justified across all strengths of enoxaparin sodium as a result of this decision.

More information

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.