WITHDRAWAL OF MIXTARD 30 in ADULTS*
This document has been prepared to inform clinicians involved in assisting patients to change insulins following NovoNordisk’s announcement in late June 2010 that Mixtard 30 is to be withdrawn in the UK by the end of the year.
The products to be discontinued include:
Mixtard 30 10ml vial : Mixtard 30 Penfill 3ml cartridge : Mixtard 30 Innolet
This guidance note aims to describe a pathway that clinicians and patients can follow together with a view to reaching a conclusion about the subsititute insulin that best suits the patient’s requirement and minimises the disruption caused by a commercial decision beyond the control of either party. In all negotiations, it should be remembered that the patient, or a carer, is the insulin user and their preferences should be given all due consideration. Transfer to animal insulins, while a potentially available option, nevertheless encourages an obsolescent option and will not be considered further. Change options are described on the next page and cost implications are listed in Appendix 1.
1. For those using Mixtard 30 vials
Most patients now using needle and syringe insulin administration will have made a conscious decision to stay with this older method. It may be worth revising with them the potential advantages in terms of all-in-one portability of a pen injection device. If change to a pen injector is being contemplated, then it may also be appropriate to consider the potential advantages of premixed analogue insulin offering a range of reusable or disposable devices. The advantages of analogue insulins may be modest; the price premium is around +60%. Anyone who has tried, and then rejected pens, may remain unimpressed with newer pen devices but could be shown them if interested.
2. For those using Mixtard 30 Penfill cartridges
Such patients are likely to be using this preparation because a) they have rejected a move to premixed analogues, b) they have never been offered such a change. A description of the potential advantages of analogue insulin could be discussed in either case. A selection of disposable/reusable devices can be offered in relation to analogue insulin; substitution of Novomix 30 3ml cartridges would allow continued use of the accustomed reusable Novopen device. A choice of 2 Lilly M3 products can be offered for those wishing to have an insulin preparation closest to that being withdrawn.
3. For those using Mixtard 30 Innolet
This poses the greatest problem for changeover as there is no similar option available. The Innolet device has proved highly successful for use in a relatively small part of the insulin market. Its design features make it a good option for patients with limited manual dexterity, co-ordination, strength and vision and it is quite likely that for some patients it may represent the only currently available solution for self-management of insulin injections. As outlined in the previous paragraphs, finding a substitute insulin is relatively easy but it will be challenging for diabetes teams and patients to find a suitable insulin delivery method for such patients and cases will have to be considered on an individual basis.
* The Paediatric Diabetes Service is communicating directly and individually with their patients who use Mixtard 30
Making the Change
Any changeover is a potential opportunity to consider a variety of factors contributing to insulin management. In particular, rotation of injection sites, re-suspension (mixing) of cartridges, and especially insulin dosage could be reviewed. Many patients regularly take insulin doses that are different from those recorded in medical notes and care must be taken to negotiate doses of any new insulin based on actual current practice in terms of insulin administration. While there is unlikely to be any real difference when M3 is directly substituted for Mixtard 30, an initial dosage reduction of 10% can be considered if hypoglycaemia is a particular anxiety. A change from Mixtard 30 to an analogue mix is perhaps more likely to produce some lower blood glucose levels and an initial dosage reduction of 15-20% should be considered, along with advice on altering injection timing so that the analogue is injected immediately before or after eating. Total daily doses may well need to be titrated back upwards in due course to somewhere around previous levels.
The most important clinical consideration in the present context may be the introduction of the rapid acting component of mixed analogues which will have a quicker onset and sharper action profile than human insulin counterparts. It should be noted that some clinicians see a potential risk in using premixed analogue insulins in those who may be less able to have meals promptly following insulin injection*.
Having considered the issues described above, the following is a simple substitution ‘map’ for what can be offered:
Mixtard 30 NEEDLE & SYRINGE USERS
a) Those wishing to continue using needle & syringe should be offered Humulin M3 10ml vials.
b) Those wishing to change to a pen device but continue ‘HUMAN’ insulin can be offered Humulin M3 in either a reusable Humapen Luxura or a pre-filled pen.1
c) Those wishing to change to a pen device and change to an analogue insulin can be offered Novomix 30 or Humalog Mix 25 for use in their respective reusable (Novopen, Humapen Luxura) or disposable (Flexpen, KwikPen) devices.
Mixtard 30 PEN USERS
a) Those wishing to continue using a pen device and a ‘HUMAN’ mixed insulin preparation can be offered Humulin M3 in either a reusable Humapen Luxura or a pre-filled pen.1
b) Those wishing only to continue using a Novopen should be offered Novomix 30 3ml cartridges.
c) Those wishing to change to an analogue mixture can be offered Novomix 30 or Humalog Mix 25 for use in their respective reusable (Novopen, Humapen Luxura) or disposable (Flexpen, KwikPen) devices.
Mixtard 30 INNOLET USERS
a) Those potentially able to continue self-injection should be offered any of the above injection methods/devices to find which, if any, offers a solution for them. Any insulin mixture is appropriate but note the concern (*above) of some at using analogue mixes in frail patients.
b) For those unable to continue self-injection the insulin choice is similar; the delivery method will depend on negotiation with the injector.
Ken McHardy NHSG
1st July 2010
1. Humulin M3 is available in a Lilly pre-filled pen but not in the newer KwikPen until September 2010.
Appendix 1
SUBSTITUTIONS FOR MIXTARD 30 – Cost Implications
Briefly, analogue insulins are considerably more expensive than ‘human’ insulins, pre-filled pens are slightly more expensive than insulin cartridges and 10ml vials of Humulin M3 are substantially more costly than vials of Mixtard 30 but still cheaper than pen insulins. The following information refers only to costs of the product listed and takes no account of other material or time costs that may be associated with any particular method of insulin delivery.
It is also of note that Lilly reduced prices of M3 pen formulations in April 2010 below those quoted in the current British National Formulary (No 59, March 2010).
Mixtard 30 NEEDLE & SYRINGE USERS
a) Those wishing to continue using needle & syringe should be offered Humulin M3 10ml vials.
o Humulin M3 10ml vial @ £15.68 [+110%]
b) Those wishing to change to a pen device but continue ‘HUMAN’ insulin can be offered Humulin M3 in either a reusable Humapen Luxura or a pre-filled pen.
o Humulin M3 5x3ml cartridges @ £19.08 [+70%] OR 5x3ml pre-filled pens @ £28.44 [+153%].
c) Those wishing to change to a pen device and change to an analogue insulin can be offered Novomix 30 or Humalog Mix 25 for use in their respective reusable (Novopen, Humapen Luxura) or disposable (Flexpen, Kwikpen) devices.
o Novomix 30 5x3ml cartridges @ £29.43 [+162%] OR 5x3ml Flexpens @ £32.00 [+185%]
o Humalog Mix 25 5x3ml cartridges @ £29.46 [+163%] OR 5x3ml KwikPens @ £30.98 [+176%]
Mixtard 30 PEN USERS
a) Those wishing to continue using a pen device and a ‘HUMAN’ mixed insulin preparation can be offered Humulin M3 in either a reusable Humapen Luxura or a pre-filled pen.
o Humulin M3 5x3ml cartridges @ £19.08 [cost neutral] OR 5x3ml pre-filled pens @ £28.44 [+49%]
b) Those wishing only to continue using a Novopen should be offered Novomix 30 3ml cartridges.
o Novomix 30 5x3ml cartridges @ £29.43 [+54%]
c) Those wishing to change to an analogue mixture can be offered Novomix 30 or Humalog Mix 25 for use in their respective reusable (Novopen, Humapen Luxura) or disposable (Flexpen, Kwikpen) devices.
o Novomix 30 5x3ml cartridges @ £29.43 [+54%] OR 5x3ml Flexpens @ £32.00 [+68%]
o Humalog Mix 25 5x3ml cartridges @ £29.46 [+54%] OR 5x3ml KwikPens @ £30.98 [+ 62%]