Decision to award sole supply of venlafaxine

Removal of the 225 mg strength

Patients currently taking the 225 mg strength of venlafaxine will need to transition to a more complicated medication regimen, increasing the patient’s pill burden and potentially cost (i.e. 2 prescription co-payments rather than one depending on what combination of strengths is used), which could impact on patient compliance and therefore health outcomes.

We acknowledge there will be an inconvenience to the very small group of patients (~1,500 out of a total 45,000 patients receiving funded venlafaxine treatment) taking the 225 mg tablets.To remain on funded treatment patients could take:

• 3 x 75 mg capsules; or

• 1 x 150 mg capsule and 1 x 75 mg.

People will be able to choose which option works best for them.  It is correct that if they choose to take one 150 mg capsule and one 75 mg capsule they would likely have to pay a co-payment for each strength (i.e. 2 x $5), while those who choose to take three 75 mg capsules would pay one co-payment ($5).  Co-payments are determined and administered by the Ministry of Health.

Appearance/Dosage/Titration

1. The capsule actually contains extended release tablet(s).

2. Are the strengths easy to differentiate?

3. Is there data on crushing those tablets for the purpose of administration to acute hospital admission patients with nasogastric tubes who will otherwise have significant withdrawal issues?

4. Some people open the Efexor XR capsules and remove a few pellets to slowly titrate their dose.  They will not be able to do this with the Enlafax XR capsules.

1. Key comparisons between Enlafax XR and the currently funded brands are detailed in Table 1 below.  Inside the Enlafax XR capsules are one, two or three, small tablets.  This differs from the contents of the Efexor-XR brand capsule which contains small pellets.

2. The appearance of the Enlafax XR capsules is similar to the Efexor-XR capsules but is noticeably different from Arrow-Venlafaxine XR tablets. There is a slight difference in appearance with the 37.5 mg presentation where the proposed Enlafax XR capsule is larger and a single colour. We consider the three strengths are easy to differentiate with colour-coded outer packaging and blister pack foils. The capsules themselves are also different colours with “37.5”, “75” or “150” printed on them, as appropriate (See Table 1 below). Enlafax XR will be packaged in calendar packs (blister foils with the days of the week printed on the reverse) similar to the Efexor-XR brand.

3. Dividing, crushing, chewing or dissolving the tablets contained in the capsules would be an off-label use of the product, and could lead to rapid release and absorption of the venlafaxine and is thus not recommended. To our knowledge there is no data on this off-label use. We note that a 1% DV limit applies to DHB hospitals so other brands could be used for patients with nasogastric tubes; however, these same issues would exist with any extended-release formulation of venlafaxine.

4. The recommendation for Efexor XR is that the capsules must be swallowed whole; titrating in this way is not recommended for Efexor XR. Similarly, dividing, crushing, chewing or dissolving the tablets contained in the Enlafax XR capsules would be an off-label use of the product and is not recommended.

Stat Dispensing

1. Three responders commented on the proposal to implement stat dispensing given the risks associated with overdose. They considered that:
   1. If the proposal is approved, venlafaxine should be made a safety medicine so prescribers have the discretion to adjust supply where they know risk is higher.
   2. The new brand of venlafaxine continue as monthly dispensing for a transition period past 1 September 2017 until all patients have transitioned and are stable.
   3. Encouraging this patient group to interact less with health professionals doesn’t appear to be in the patient’s best interests.
2. A fourth responder considered that the proposal would result in additional dispensing time and expense in pharmacies due to the perceived need for pharmacies to split blister packs and add six capsules to the proposed 84 capsule pack to make up a 90 pack, with the potential for errors, wastage and spoilage.

1. PHARMAC has received advice from members of the Mental Health Subcommittee of PTAC that stat dispensing is appropriate for venlafaxine. We note that the risk of overdose is inherent in depression and that with all medications there are safety concerns of overdose, but consider that this is best managed by clinicians as part of their overall care for their patients. We note that, under normal supply conditions, seven out of the 17 currently-funded antidepressant medicines are able to be dispensed stat. 
   1. We note that prescribers are able to modify the dispensing frequency on a prescription if they deem a particular patient would be at risk if receiving three months’ of medication all-at-once.  A pharmacist may also alter the dispensing to monthly lots without prescriber approval, to meet patients’ needs. 
   2. Following consideration of the feedback, PHARMAC has decided to introduce stat dispensing after the transition period i.e. from 1 December 2017. This is a change from the original proposal, which was that stat dispensing would commence on 1 September 2017, and will allow all patients time to stabilise on the new brand prior to receiving three months’ supply at once.
   3. We note the concern. Please see 1. a) above.
2. We note that all incumbent strengths are packaged as 28 tabs/caps and that in just over half of the dispensings they are dispensed as 30s. Therefore this decision will not change the amount of work currently undertaken by pharmacists.

Patient Group Concerns and bioequivalence

Four responders raised safety concerns for what they perceived as a vulnerable patient group, who find changing to generics very difficult. Noting negative experiences, adverse reactions, potential for increased hospitalisations and one specific patient experience of a similar previous brand switch (fluoxetine).

One respondent noted that they were unaware of any data on comparative bioequivalence between Enlafax XR and Arrow-Venlafaxine XR.

Enlafax XR has met Medsafe’s standards for registration for use in New Zealand, including demonstration of bioequivalence to Efexor XR. This means that patients can expect to get the same clinical benefit from Enlafax XR as from their current brand.  We understand that changing brands can be challenging for some patients, and PHARMAC will develop a range of resources to support health professionals and patients during the brand change. 

As with any generic to generic switch, our view is that if both generics have demonstrated bioequivalence against the innovator brand, then patients could expect to get the same clinical benefit from either generic brand.

Implementation & Brand Switch Fee

One respondent considered that:

1. Patients would need additional information and support from their prescriber and pharmacist.
2. It would be important for written and online information to be prepared for prescribers and pharmacists well in advance to prepare these patients for the future brand change.
3. It would be essential that a Brand Switch Fee be applied to all strengths of Enlafax XR from 1 September 2017.

1. PHARMAC will develop patient information that can be used by healthcare professionals to help support patients with a change in brand.  Information will be able to be viewed and downloaded from the PHARMAC website.
2. PHARMAC will develop online material for healthcare professionals to ensure they have good information to support patients through the brand change.
3. A Brand Switch Fee has been applied for pharmacists to claim (one fee per patient) in recognition of the additional support patients will require.

Sole Supply

One respondent did not think a sole supply agreement for venlafaxine was appropriate, noting several issues common to abrupt supply disruptions with any sole supply agreement.

PHARMAC notes that having multiple brands of a product in a market does not necessarily improve security of supply.  When there is one supplier, our experience is that supplier forecasting is typically more accurate, which helps reduce the risk of out-of-stock situations.

Further, in exchange for market exclusivity, the supply contracts we have in place require suppliers to agree to rigorous conditions to prevent and manage potential out-of-stocks.

We note that prior to the listing of Arrow-Venlafaxine XR in 2011 there was only one supplier/one brand in the market for at least six years.

Registration Status

One respondent raised a concern regarding the registration status of Enlafax XR with Medsafe.

Enlafax XR was registered by Medsafe on 12 March 2009.