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

Medicines Consultation Closed

PHARMAC is seeking feedback on a proposal relating to certain medicines in the neurology, immunology and nephrology therapeutic areas to take effect from 1 July 2017.

In summary:

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

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by Friday, 12 May 2017 to:

Adrienne Martin
Senior Therapeutic Group Manager/Team Leader
PHARMAC

Email: consult@pharmac.govt.nz

Fax:     04 460 4995
Post:    PO Box 10 254, Wellington 6143

All feedback received before the closing date will be considered by PHARMAC’s Board (or its delegate) prior to making a decision on this proposal.

Feedback we receive is subject to the Official Information Act 1982 (OIA) and we will consider any request to have information withheld in accordance with our obligations under the OIA. Anyone providing feedback, whether on their own account or on behalf of an organisation, and whether in a personal or professional capacity, should be aware that the content of their feedback and their identity may need to be disclosed in response to an OIA request.

We are not able to treat any part of your feedback as confidential unless you specifically request that we do, and then only to the extent permissible under the OIA and other relevant laws and requirements. If you would like us to withhold any commercially sensitive, confidential proprietary, or personal information included in your submission, please clearly state this in your submission and identify the relevant sections of your submission that you would like it withheld.  PHARMAC will give due consideration to any such request.

Details of the proposals

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 would 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 2 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 2 inj available on a PSO.

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

Midazolam background

Midazolam injections are currently funded without restrictions.

In November 2016, the Neurological Subcommittee of PTAC reviewed requests to make midazolam injection available on a PSO for use (buccally) in seizure control in status epilepticus. The Subcommittee considered that midazolam administered buccally has the same or similar therapeutic effect to rectal diazepam. The Subcommittee noted diazepam was a longer acting benzodiazepine. However, Members considered that midazolam may be a more suitable alternative as it is easier to administer, allows dose titration (via dripping the solution buccally) and was not able to be expelled, as is the case with rectal diazepam.

The Subcommittee recommended that two ampoules of midazolam injection (5 mg per ml, 3 ml plastic ampoules) for the treatment of status epilepticus be available on a PSO with a high priority. This recommendation was endorsed by PTAC at its February 2017 meeting. [PDF, 260 KB]  

Note that the Mental Health Subcommittee of PTAC also reviewed the above request at its November 2016 meeting and considered that the lower strength (1 mg per ml, 5 ml) should also be made available on a PSO for the same use as its use would be less risky with regard to an overdose in children. This view was also endorsed by PTAC at its February 2017 meeting.

Infliximab – widen access for neurosarcoidosis and Behçet’s disease

  • Restrictions on the use of infliximab injection 100 mg (Remicade) in DHB hospitals would 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

Re-assessment required after 18 months

Neurologist

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:
    1. IV cyclophosphamide has been tried; or
    2. Treatment with IV cyclophosphamide is clinically inappropriate.

Continuation – neurosarcoidosis

Re-assessment required after 18 months

Neurologist

Either:

  1. A withdrawal period has been tried and the patient has relapsed; or
  2. All of the following:
    1. A withdrawal period has been considered but would not be clinically appropriate; and
    2. There has been a marked reduction in prednisone dose; and
    3. Either:
      1. There has been an improvement in MRI appearances; or
      2. Marked improvement in other symptomology.

Initiation – severe Behçet's disease

Re-assessment required after 4 months

All of the following:

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

a) Behçet’s disease diagnosed according to the International Study Group for Behçet’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.

b) 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 Behçet'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):

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

Continuation- ocular inflammation

Re-assessment required after 12 months

Both:

  1. Patient has had a good clinical response to initial treatment; and
  2. Either:
    1. A trial withdrawal of infliximab has been trialled and patient has relapsed after trial withdrawal; or
    2. Patient has Behcet’s disease

Both

  1. Either:
    1. Following 3 initial doses, the patient has had a good clinical response and must be reassessed for continuation at 12 months; or
    2. Following 12 months’ treatment, and every 12 months thereafter, the patient must be reassessed for continuation and meet one of the following:
      1. 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); or
      2. Sustained steroid sparing effect, allowing reduction in prednisone to <10mg daily, or steroid drops less than twice daily if under 18 years old; and
  2. 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.
  • No other changes to the infliximab restriction criteria are proposed.

Infliximab background

Infliximab is a monoclonal antibody tumour necrosis factor (TNF)-alpha inhibitor that is used to treat a range of immunological conditions. It is administered by intravenous infusion and is currently funded in DHB hospitals subject to restrictions for use in graft versus host disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, severe and chronic ocular inflammation, pulmonary sarcoidosis, Crohn’s disease, severe ulcerative colitis and plaque psoriasis.

In November 2015, the Neurological Subcommittee of PTAC discussed the treatment options for patients with neurosarcoidosis and noted an unmet clinical need in patients who did not respond to, or could not take, first line options (corticosteroids). The Subcommittee recommended that infliximab be funded for neurosarcoidosis subject to the criteria outlined above with a high priority. This recommendation was endorsed by PTAC at its February 2016 meeting.

PHARMAC has assessed 8 Named Patient Pharmaceutical Assessment (NPPA) applications for infliximab for the treatment of neurosarcoidosis since July 2013, all of which were approved. We estimate that approximately 10 patients per year with neurosarcoidosis would be eligible for treatment with infliximab under the proposed criteria.

Following discussions and recommendations from the Dermatology and Ophthalmology Subcommittees in relation to an application to fund TNF-alpha inhibitors for treatment-refractory Behçet’s disease, PTAC recommended that that the funding of infliximab should be widened to include ocular and non-ocular manifestations of Behçet's disease, subject to the restrictions outlined above, with a medium priority.

We estimate that approximately 25 patients per year with Behçet's disease would meet the proposed criteria.

More information about these two changes, including links to relevant PTAC and Subcommittee minutes, can be found in the Application Tracker records for infliximab at: https://connect.pharmac.govt.nz/apptracker/s/global-search/Infliximab(external link)

In addition to the above two new uses, we are proposing some changes to the criteria for infliximab for ocular inflammation in line with recommendations from the Ophthalmology Subcommittee at its meeting in 2014, and we also propose to remove the reference to Behçet’s disease as this would not be necessary if the proposed new Behçet’s disease restrictions were implemented.

Relevant minutes from the Subcommittee’s discussion. [PDF, 135 KB]

Enoxaparin sodium – widen access to include use in home haemodialysis

  • Access to enoxaparin sodium injections (Clexane) would 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.
  • No changes are proposed for the Special Authority criteria for the indication of ‘venous thromboembolism other than in pregnancy or malignancy’.

Enoxaparin background

Enoxaparin sodium is a low molecular weight heparin (LMWH) anticoagulant which is administered by subcutaneous injection. It is used for the prevention and treatment of deep-vein thrombosis in surgical and medical patients, treatment of unstable angina and myocardial infarction and for the prevention of thrombus formation in haemodialysis. It is also used for treatment of venous thromboembolism in pregnancy and the prevention of thrombus formation in cardioversion for atrial fibrillation (unapproved indications). There are no restrictions on the use of enoxaparin sodium in DHB hospitals.

At its most recent meeting, in December 2016, the Nephrology Subcommittee of PTAC reviewed a funding application to widen access to enoxaparin for people undergoing haemodialysis at home or in a community setting. The Subcommittee recommended that access be widened, only if cost-neutral to the Combined Pharmaceutical Budget.

Traditionally, anticoagulation during haemodialysis has been achieved using unfractionated heparin. LMWHs such as enoxaparin sodium have been found to be equally effective, and their use is now supported in major guidelines. Enoxaparin sodium is easier to administer, given that only one bolus injection is sufficient to cover most session durations.

The Subcommittee considered the dosage of enoxaparin used in clinical practice is likely to be 0.3–0.5 mg/kg administered into the venous circuit at the start of the dialysis session. Enoxaparin costs are therefore dependent on patient weight; however, we consider they are similar to unfractionated heparin at current prices.

Approximately 500 people are undergoing haemodialysis at home or in a community setting using unfractioned heparin. This proposal would allow funded access to enoxaparin in the community for these patients.

Minutes of the Subcommittee’s discussion will be published on PHARMAC’s website as soon as they are available.