Decision to fund an additional brand of budesonide with eformoterol

Many responders were supportive of the proposal to fund an additional brand of budesonide with eformoterol, noting that:

• Increasing competition was favourable, as it would widen options to patients in New Zealand, especially in light of the recent New Zealand Asthma guidelines that promote the use of anti-inflammatory reliever therapy.
• The presence of only one option of inhaler may have posed a barrier to patients receiving the recommended treatment for asthma, in particular for patients with lower levels of dexterity or those who like an MDI style of inhaler.
• The DuoResp Spiromax inhaler appears easy to use, which could decrease error frequency if taught properly. The presence of a dose counter which changes colour when time to pick up repeat prescription was also noted.
• Dry powder inhalers produce less greenhouse emissions than aerosols, which may be preferable for some patients.

PHARMAC has noted these supportive responses.

Some responders were concerned whether this would be funded for use as Anti-inflammatory reliever (AIR) and AIR plus maintenance therapy

NZ adolescent and adult asthma guidelines(external link)

PHARMAC understands that the budesonide with eformoterol 160/4.5 product (200/6) will be Medsafe-approved for use as:

• Anti-inflammatory reliever therapy (patients with mild disease).
• Anti-inflammatory reliever plus maintenance therapy.

Some responders noted that this is another dry powder inhaler (DPI) and that feedback from both health professionals and patients has indicated that a metered dose inhaler device is preferred. They queried if PHARMAC should enable Vannair, the currently funded budesonide with eformoterol pMDI to be used as anti-inflammatory reliever or anti-inflammatory reliever plus maintenance therapy.

Vannair is not Medsafe-approved for use as SMART or AIR therapy.

PHARMAC understands that there are no budesonide with eformoterol pMDI products that have Medsafe approval for anti-inflammatory reliever or anti-inflammatory reliever plus maintenance therapy at this time.

We will continue to liaise with suppliers and monitor the regulatory setting for any approvals of any budesonide with eformoterol pMDI products for the AIR or AIR plus maintenance therapeutic indications.

Some responders noted that the listing of DuoResp Spiromax would add an additional inhaler to an already large list of inhalers available in NZ.

Noted, however as stated in the consultation, the intention here is to introduce and promote competition in the budesonide with eformoterol market.

Some responders considered that the addition of an inhaler with an expiry of 6 months to be a risk, and noted that the DuoResp Spiromax product must be discarded within 6 months of removing from the foil wrapping, rather than discarded upon the shelf-life of the product expiring.

PHARMAC considers it important that healthcare professionals explain how these inhalers are used and that these should not be used for longer than 6 months once opened. This information is clearly indicated on the packaging of each inhaler.

It is considered important that pharmacists, prescribers, practice nurses, and others in the healthcare team communicate to patients that there is an expiry of 6-months from the date of opening of the product (similar to insulin and eye drops).

We note the importance of pharmacists reminding patients to note the date when they remove the inhaler from the foil to track the six-month expiry.

Some responders noted that as there are only 2 strengths available, there is a decreased ability to down-titrate for this product.

PHARMAC notes this, however Teva Pharma does not currently have a product that is equivalent to the Symbicort Turbuhaler 100/6, and therefore, this has not been included.

Some responders queried exactly how much lactose is in each of the DuoResp Spiromax products.

Lactose is an inactive ingredient to ensure consistent dosing commonly used in many dry powder inhalers.

DuoResp Spiromax 160 micrograms / 4.5 micrograms inhalation powder contains approximately 5 milligrams of lactose per dose (as monohydrate).

This has been taken from the SmPC for this product (smpc)(external link).
This is greater than the amount of lactose in each dose from the Symbicort Turbuhaler 200/6.

DuoResp Spiromax 320 micrograms / 9 micrograms inhalation powder contains approximately 10 milligrams of lactose per dose (as monohydrate).

This has been taken from the SmPC for this product (smpc)(external link).
This is greater than the amount of lactose in each dose from the Symbicort Turbuhaler 400/12.

This amount of lactose does not normally cause problems in lactose intolerant people. If allergic to lactose, patients should speak to their healthcare professional about alternative inhaler options.

Some responders queried what the lung deposition of budesonide and eformoterol from this product is, and if it is similar to the currently listed budesonide with eformoterol products.

DuoResp Spiromax has been shown to be equivalent to Symbicort Turbuhaler in both pulmonary and systemic deposition for the equivalent 200/6 and 400/12 doses.

PHARMAC understands that pharmacokinetic studies have shown DuoResp Spiromax to be equivalent to Symbicort Turbuhaler in both pulmonary and systemic deposition for the equivalent 200/6 and 400/12 doses. Members of the Respiratory Subcommittee consider these studies to be a valid surrogate for evaluating regional lung deposition.

Members of the Respiratory Subcommittee of PTAC consider that clinically important differences in regional lung distribution are not expected between pMDIs and DPIs, as the clinical outcome studies are good with both devices. However, members acknowledge they were unable to find any available direct comparisons between DuoResp Spiromax and Vannair.

Some responders recommended that the high strength (400/12) product not be funded, as an active recommendation in the NZ asthma guidelines is made that it not be used as anti-inflammatory reliever therapy. Noted that there is a risk that the 400/12 product might be used for reliever therapy, which would expose the patient to significant risk from excessive dosing of both the inhaled corticosteroid (ICS) and long acting beta agonist (LABA) components

The Symbicort Turbuhaler 400/12 presentation was listed in the Pharmaceutical Schedule in 2006, and the DuoResp Spiromax 320/9 (400/12) is considered equivalent. There remains a number of patients prescribed this strength, and PHARMAC considers it would be difficult at this stage to exclude this apparent high-need population, who are apparently benefitting from being prescribed the high strength formulation, from any potential commercial process for this market without further clinical advice.

In addition, there is a dispensing restriction on the 400/12 strength of Symbicort Turbuhaler, restricting its use to no more than 2 doses per day. This restriction will also be put in place for the DuoResp Spiromax product.

While we consider whether a product is available or not should not dictate what are clinical decisions, we intend to seek further clinical advice within the next 6 months from the Respiratory Subcommittee around the need to retain on or remove from the Schedule all high dose budesonide with formoterol products.

Some responders highlighted there could be confusion with DuoResp Spiromax:

• due to its similar style to an MDI, and patients may try to use it in a spacer or shake prior to use, and thereby not actually receive their dose.

• The DuoResp Spiromax inhaler has been designed specifically to look and feel like a conventional MDI (Canonica et al. 2015;28:309-19(external link)).

  PHARMAC notes the similarities between the DuoResp Spiromax product and that of MDIs, and consider it important that healthcare professionals explain how these inhalers are used. We also note possibly contrary views amongst responders, as other responders, and members of the Respiratory Subcommittee of PTAC considered the look and feel of the device to be a positive option for some patients.  

  In addition, PHARMAC’s Respiratory Procurement Advisory Group noted that there may be greater ease of administration for patients with reduced manual dexterity with the DuoResp Spiromax.

• given its similar name to a currently listed long-acting muscarinic agonist (LAMA), ie. Spiriva Respimat®

• PHARMAC understands the potential confusion that could arise given DuoResp Spiromax’s similar naming convention to a currently listed long-acting muscarinic agonists (LAMA), Spiriva Respimat®. However, we consider this to be a low risk, as LAMAs currently require an endorsement by the prescriber that the patient has a diagnosis of chronic obstructive pulmonary disease (COPD). Such consideration regarding similar brand names is also taken into account by Medsafe during its evaluations.

• as Symbicort and Vannair are currently dosed as 200/6 and 400/12; responders recommended that the equivalent doses be clearly outlined in the Pharmaceutical Schedule and Medsafe datasheet.

• The doses of budesonide and eformoterol delivered via the Duoresp Spiromax inhaler are 160/4.5 mcg and 320/9 mcg. These correspond to metered doses of 200/6 mcg and 400/12 mcg, respectively, and are equivalent to these doses delivered by the currently funded Symbicort Turbuhaler brand. The metered dose is the dose available within the inhaler to be dispensed per inhalation. The delivered dose is the dose available for inhalation per inhalation. PHARMAC understands that the Medsafe datasheet will clearly state that these are equivalent. In addition, the equivalent dose would also be listed in the schedule and on the packaging of each inhaler so that this is made as clear as possible.

• with the DuoResp Spiromax product being only registered for adults 18yrs and over, while Symbicort is registered for patients 12yrs and over

• PHARMAC understands that initially the DuoResp Spiromax inhaler will be Medsafe approved for use in adults 18 years and over. We note that once the Duoresp Spiromax inhaler is approved for use in the adolescent age group by the EMEA in the European Union, a submission to Medsafe that includes this age group in New Zealand would occur. Members of the Respiratory Subcommittee consider this not to be a clinical risk, and note that the 100/6 and 200/6 strengths of Symbicort Turbuhaler are Medsafe-approved for use in patients over four years of age. Members considered that communication via the datasheet and other communications will suffice.