Decision to decline inactive medicines funding applications

Aripiprazole depot injection for schizophrenia

Aripiprazole depot is relatively free from adverse effects including extrapyramidal side effects, weight gain, dyslipidaemia, impaired glucose tolerance, sedation, and sexual dysfunction.

It would be highly desirable to have access to a funded treatment that avoided adverse effects, particularly for the following reasons:

• Māori and Pacific Island populations often experience the metabolic effects of depot antipsychotics. It would be desirable to have a funded depot antipsychotic that doesn’t cause metabolic effects.
• Some people receive compulsory treatment under the Mental Health Act. There is a greater expectation of “do no harm” in this setting.

A recent study comparing the use of aripiprazole depot and usual care on the time to first hospitalisation in early- phase schizophrenia provides evidence that aripiprazole depot is beneficial over usual care.

We note the availability of updated evidence. We have decided not to progress aripiprazole depot injection for schizophrenia to a decline decision at this time, pending further clinical advice.

Asenapine for bipolar 1 disorder or schizophrenia

Asenapine will appear high on a list of recommended treatments for mania in the new Royal Australian and New Zealand College of Psychiatrics (RANZCP) clinical practice guidelines for mood disorders (2020).

We acknowledge that asenapine is included in the recent   RANZCP mood disorder guidelines. A guideline recommendation is not enough to support funding asenapine at a cost when our clinical advisors considered that it provides no additional clinical benefit when compared to other, less expensive treatment options.

We would be happy to reopen the application if evidence of benefit over other treatment options can be provided.

Bimatoprost 0.03% and timolol maleate 0.5% for open-angle glaucoma or ocular hypertension

Currently there are only two funded combination medicines that include ophthalmic prostaglandin analogues (PG). Data indicates greater intraocular pressure (IOP) lowering effects of dual therapy regimens of a PG combined with a beta blocker compared to combinations of two non-PG medicines.

Compared with therapy with multiple individual treatments, use of fixed combination therapy reduces treatment complexity, may improve adherence, decreases cumulative exposure to preservatives, reduces benzalkonium chloride (BAK) associated ocular discomfort and ocular surface disease symptoms, decreases the risk of insufficient dosing and may contribute to better long-term stability of IOP control.

We appreciate there is support for combination eye drop therapy with beta blockers and prostaglandin analogues. PHARMAC has recently awarded a tender (October 2020) for the supply of latanoprost with timolol, meaning a combination product will be available from 1 April 2021. Declining this application does not prevent us from considering other combination products in the future.

Brimonidine tartrate eye drops 0.15% for glaucoma

Brimonidine offers several benefits:

• Brimonidine offers neuroprotective benefits and is safe to use in pregnancy within the first two trimesters.
• It is better tolerated by people with a BAK allergy.
• In the Low-pressure Glaucoma Treatment study, patients treated with brimonidine were less likely to have field progression compared to those receiving timolol.
• Another study demonstrated that brimonidine-purite 0.15% was better tolerated, with lower rates of allergic conjunctivitis and increased satisfaction when compared to brimonidine-purite 0.2% while still showing a similar IOP lowering effect.

Declining this application only closes this funding application for brimonidine 0.15% eye drops. PTAC reviewed this funding application in February 2008 [PDF, 208 KB] and considered that brimonidine 0.15% with the purite preservative had the same or similar therapeutic effect as brimonidine tartrate 0.2% eyedrops. PTAC recommended that brimonidine 0.15% eye drops be listed on the Pharmaceutical Schedule only if cost neutral to brimonidine 0.2% eye drops. Following PTAC’s recommendation, we include brimonidine tartrate eye drops 0.15 – 0.2% in the annual tender process, although we note that we have yet to receive acceptable bids for the 0.15% strength.

We acknowledge the comments that a particular brand of brimonidine tartrate 0.15% contains the purite preservative rather than the BAK preservative. A BAK-free presentation of pilocarpine is funded for patients who do not tolerate BAK-containing formulations of brimonidine, brimonidine with timolol or pilocarpine eye drops.

Ketotifen fumarate for ocular allergy

There are currently no funded antihistamine eye drops.

We understand there are no funded antihistamine eye drops listed in the Pharmaceutical Schedule. We have decided not to decline this application at this time. We will consider options and seek advice where necessary.

Travoprost and timolol for glaucoma

Currently there are only two funded combination medicines that include ophthalmic PG. Data indicates greater IOP lowering effects of dual therapy regimens of a PG combined with a beta blocker compared to combinations of two non-PG medicines.

Compared with therapy with multiple individual treatments, use of fixed combination therapy reduces treatment complexity, may improve adherence, decreases cumulative exposure to preservatives, reduces benzalkonium chloride BAK associated ocular discomfort and ocular surface disease symptoms, decreases the risk of insufficient dosing and may contribute to better long-term stability of IOP control.

We appreciate there is support for combination eye drop therapy with beta blockers and prostaglandin analogues. PHARMAC recently awarded a tender (October 2020) for the supply of latanoprost with timolol, meaning a combination product will be available from 1 April 2021. Declining this application does not prevent us from considering other combination products in the future.

Enzalutamide for metastatic, castration-resistant prostate cancer

Enzalutamide is available and funded in other comparable health jurisdictions. While it is considered clinically equivalent to abiraterone, there is a role for both medicines if one is not tolerated.

A small proportion of men will not be able to tolerate abiraterone due to adverse effects. There is no funded alternative novel hormonal agent for men with castration-resistant prostate cancer who have liver dysfunction.  Severe liver toxicity occurs rarely in clinical practice (1% or less in clinical trials). Docetaxel chemotherapy may not be suitable as another life prolonging therapy. Enzalutamide is primarily renally excreted and can be used safely in men with pre-existing liver dysfunction or abiraterone induced liver toxicity.

Additional data is now available to support use of enzalutamide.

Noting the new information received during consultation, we have decided not to progress this application for a decline decision at this time pending further advice and information.

Nab-paclitaxel for metastatic breast cancer

Some concerns were raised that an application for nab-paclitaxel submitted in February 2018 was not reviewed by the Cancer Treatments Subcommittee of Pharmacology and Therapeutics Advisory Committee (PTAC) (CaTSoP).

Questions were also raised as to why there is an alternative brand allowance for tendered products, but there is no alternative treatment allowance for patients who cannot tolerate non-tendered, funded medicines.

Nab-paclitaxel is now standard therapy for many cancers and is being used concurrently in combination with newer agents in clinical trials. It is the standard of care in comparable developed countries, including countries that would be considered ‘poorer’ than NZ. Nab-paclitaxel has fewer side effects and is less toxic compared to other treatment options.

There are major advantages of nab-paclitaxel over paclitaxel, with virtually no infusion reactions and a shorter infusion time (30 minutes rather than 60). This would have a major impact on resource use in cancer treatment units.

We have decided not to progress nab-paclitaxel for metastatic breast cancer to a decline decision at this time, pending further clinical advice, including from CaTSoP.

In this case, PTAC considered the application for nab-paclitaxel (May 2019) [PDF, 787 KB]. We acknowledge the concern that the application was not reviewed by CaTSoP. PTAC considers funding proposals across all therapeutic areas and may seek specialist advice from its Subcommittees, including from CaTSoP. PTAC has a broad membership and has an expertise in critical appraisal of evidence.

Alternative brand allowances are a contractual mechanism to manage use of other brands of the same medicine if required. The same challenges apply for tendered products if a patient is unable to tolerate a medicine due to adverse effects related to the active component. We are always interested to understand where there is a health need for alternative treatments.

The Exceptional Circumstances Framework enables PHARMAC to consider funding decisions for individuals in exceptional circumstances that fall outside of the Pharmaceutical Schedule funding process. This includes the Named Patient Pharmaceutical Assessment (NPPA) Policy and other processes through which PHARMAC considers exceptional circumstances when, due to specific clinical circumstances, a funded treatment may be clinically unsuitable.

Vinorelbine (oral) for non-small cell lung cancer

There are oral vinorelbine products now available in New Zealand undergoing Medsafe assessment.  

We have decided not to progress oral vinorelbine for non-small cell lung cancer to a decline decision at this time, pending ongoing discussions with interested suppliers. The application remains under consideration for funding.

Cholecalciferol (also known as colecalciferol or vitamin D) 1000 IU tablets for vitamin D deficiency

The current recommended treatment for children with vitamin D deficiency is for intermittent high dose vitamin D therapy (also known as STOSS). The funded treatment options for vitamin D deficiency, 50000 iu tablets or Pura drops for babies/young infants can cause issues within the children/adolescent age groups. Specifically:

• the drops are unsuitable for intermittent high dose vitamin D therapy (STOSS).
• high dose therapy with the 50000 iu tablets is potentially unsafe if a child has elevated PTH levels, because it will lead to symptomatic hypercalcaemia. To avoid this risk, serial PTH levels must be measured. By contrast, this is not a risk with the lower dose 1000 iu tablet. It can therefore be used immediately in all children with known vitamin D deficiency without further testing/monitoring.

We note the comments in relation to the suitability of current treatment options for the children/adolescent age groups. We have decided not to progress cholecalciferol 1000 IU tablets to a decline decision at this time, pending further clinical advice.

Lorenzo's oil for adrenoleukodystrophy

Request that Lorenzo’s oil be listed for any future patients with adrenoleukodystrophy.

This application is for the pre-mixed Lorenzo’s oil solution. The components of Lorenzo’s oil are listed on Section H of the Pharmaceutical Schedule and can be prepared in DHB hospitals. We note that, to date, PHARMAC has only received a very small number of NPPA exceptional circumstances applications for Lorenzo’s oil for use in the community. Noting the small patient numbers, PHARMAC considers that NPPA is an appropriate route to access Lorenzo’s oil in the community.

NutriniDrink paediatric oral feed powder

There is no other nutritionally complete paediatric powdered supplement available on prescription.

Powdered formulations can be particularly useful were there are refrigeration issues, flexibility to decrease or increase the calorie content is required, added nutrition needs to be disguised and if there are supply issues. Growing environmental concerns means people are seeking lower waste options, including tinned products.

We note the comments in relation to the availability of a nutritionally complete paediatric powdered supplement. However, We have been informed there is no product currently available. We would be happy to consider an application for a powdered, nutritionally complete, paediatric supplement should one be made available in New Zealand.

Fortijuice oral feed for malnutrition

There are currently only milk style oral nutritional supplements funded. There is no funded alternative for patients who do not like milk style supplements.

Fortijuce could be useful for those patients requiring a supplement but are unable to tolerate fat (Fortijuce is fat free).

Fortijuce is currently a suggested brand in Section H of the Pharmaceutical Schedule. Dietitians have requested it to be also available in Section D for use in the community.

We note the comments in relation to the suitability of Fortijuice. We have decided not to progress Fortijuice oral feed to a decline decision at this time, pending further advice.

Fortisip Compact 2.4Kcal/ml oral feed for oral nutrition support

There is a similar product funding application for Fortisip Compact Protein. Will this be considered for decline at this time?

There is an unmet need in patients who are unable to consume the volume of currently funded supplements to meet their nutritional requirements. This results in poor health outcomes such as malnutrition, increased risk of infection, poor wound healing, longer hospital stays and prolonged recovery periods.  Fortisip Compact Protein may increase compliance due to the smaller volume needed to achieve required calories.

There are two funding applications for similar products and this has created some confusion. The PHARMAC Application Tracker will be updated to reflect both products.

For clarity, the product that has been declined is Fortisip Compact.

A further funding application for Fortisip Compact Protein remains active.

Apixaban for stroke prevention in atrial fibrillation

Apixaban is non-inferior to warfarin and other novel oral anticoagulants in preventing thromboembolic stroke.

Apixaban is superior to warfarin and other novel oral anticoagulants with lower risk of intracranial haemorrhage and major gastrointestinal bleed.

Further recent evidence was provided comparing apixaban with rivaroxaban.

We note the comments and recent evidence in relation to apixaban for stroke prevention in atrial fibrillation. PHARMAC has decided not to progress apixaban for stroke prevention in atrial fibrillation to a decline decision at this time, pending further clinical advice.

Sodium chloride prefilled syringes sterile pack for flushing in-situ vascular access devices

Information in support of funding sodium chloride prefilled syringes:

• The burden of catheter related complications is high.
• The cost of treating catheter related blood stream infections is high,
• The risk of unknown transmission of disease and the use of aseptic technique in addressing this. Testimonials from clinicians who have used sodium chloride prefilled syringes in the past.

The issues raised were considered during the analysis of the proposal.

In 2015, PTAC [PDF, 378 KB] recommended funding of PosiFlush XS for use in the flushing of in-situ vascular access devices only when used in a hospital sterile field environment using sterile gloves and aseptic techniques, with a high priority.

We consider that funding this product would be a fiscal risk. Analysis indicates that the cost-effectiveness is driven by how well use can be targeted to the right population. Currently, there are limited nationally consistent mechanisms to control the usage of such a product compared to the lower cost currently used alternative.

We would be happy to reactivate this application if information is provided to show how this risk could be managed, for example, through reduced pricing or the ability to specifically target use.

Ingenol mebutate for solar (actinic) keratosis lesions

There may be a benefit to ingenol when comparing it to the other treatment options. Specifically, ingenol is a shorter three-day treatment as opposed to 3 weeks or 6-12 weeks (compared to 5-FU cream and imiquimod). This time difference may provide a benefit in situations where a third party must apply the medicine. For example, with elderly patients or people with poor eyesight, dementia, physical disabilities, tremors etc.

We appreciate the feedback regarding the suitability of this product in certain situations. Medsafe(external link) information for this product advises that the approval for this product has lapsed(external link).  

Selexipag for pulmonary arterial hypertension - monotherapy, dual therapy and triple therapy

Strong support from clinicians to keep selexipag under active consideration for funding due to advantages over the other agents in this class. For example, when comparing to the alternative treatments, iloprost, requires 6-8 nebulisations a day, and epoprostenol requires burdensome maintenance of IV lines that carries a risk from sepsis and death as a consequence of poor line hygiene.

We have decided not to progress selexipag to a decline decision at this time, pending further advice.

Carbetocin for uterine atony and excessive bleeding following Caesarean section

A responder raised questions on the rationale for considering this medicine for decline, noting that it removes the requirement for oxytocin infusion to prevent post-partum haemorrhage. Providing an infusion requires a pump, IV-line, drip pole etc. All these things will interfere with a mother looking after a newborn (given that the woman is otherwise well enough to provide this care). Evidence was provided to support the use of carbetocin in this setting.

We acknowledge the feedback regarding the issues associated with the alternative treatment, oxytocin. We understand the cost difference between carbetocin and oxytocin is likely to be considerable and consider that it wouldn’t be possible to justify this additional cost in order to solely address the issues raised.

We would be happy to reactivate this application if this difference in cost could be addressed or if evidence to support there being an additional clinical benefit in the use of carbetocin above oxytocin could be provided.

 Sofosbuvir + velpatasvir for chronic hepatitis C

Sofosbuvir with velpatasvir is currently the only effective therapy for decompensated patients with genotype 3 hepatitis C.

Velpatasvir does not contain the protease inhibitor class of direct acting anti-viral medicines. Therefore, it may be suitable for patients for whom other treatments have been unsuccessful due to protease inhibitor resistance. This treatment has few drug-drug interactions, lack of contraindications based on liver function, is easy to dose and easy to administer.

Since receiving this funding application, an alternative medicine has been funded for this patient group (glecaprevir with pibrentasvir (Maviret)). Another application for sofosbuvir with velpatasvir for decompensated patients with genotype 3 hepatitis C(external link)  remains active.

With regards to the feedback about the patients with protease inhibitor resistance, an application for sofosbuvir, velpatasvir and voxilaprevir(external link) remains active. At its February 2019 meeting [PDF, 498 KB], PTAC has recommended this be listed with a medium priority for those who have been treated with a direct acting antiviral and did not achieve Sustained Virologic Response (SVR) and have evidence of Resistance associated variants (RAVs). 

Tenofovir alafenamide for chronic hepatitis B in adults

Tenofovir disoproxil is associated with side effects including nephrotoxicity, and decreased bone mineral density. Tenofovir alafenamide has greater plasma stability and more efficiently delivers tenofovir to liver cells, therefore it can provide a similar efficacy to tenofovir disoproxil, but at a lower dose. This results in less systemic exposure and therefore decreased renal and bone toxicity compared to tenofovir disoproxil. There are recognised differences in clinical outcomes between patients treated with tenofovir and patients treated with entecavir. Specifically, a growing body of evidence that tenofovir is associated with a statistically significant lower risk of liver cancer than entecavir treatment.  

We have decided to not progress this application to a decline decision at this stage, pending further information from the supplier.

Rilpivirine for HIV/AIDS

Rilpivirine is considered significantly more tolerable and with a favourable lipid profile when compared to efavirenz (the currently funded alternative). Dual combination therapy of dolutegravir and rilpivirine is recommended internationally as a treatment optimisation option for virally suppressed individuals.

Dual and triple therapy regimens should be considered to enable HIV-infected individuals’ choice and the ability to maintain adherence.

We acknowledge the feedback regarding tolerability and favourable lipid profile compared to efavirenz. This was considered by PTAC when it provided its cost-neutral recommendation [PDF, 191 KB]. No new information to support the application has been received to date.

We would welcome a funding application for dolutegravir and rilpivirine dual combination therapy.