Published: 6 December 2019

Publications

Some medicines need to be prescribed by brand

Prescriber Update 40(4): 68–69
December 2019

Generic medicines contain the same active ingredient delivered in the same way as the brand name innovator product. Suppliers of generic medicines must provide evidence that their product is bioequivalent to the innovator product before they are approved by Medsafe. Medicines are considered bioequivalent if the bioavailability (determined by the rate and extent of absorption of the active ingredient into the systemic circulation) is comparable within internationally accepted limits^1,2. Medsafe assesses bioequivalence to the innovator product during the pre-market approval process. Medsafe does not usually assess bioequivalence between different generic products.

Approved generic medicines may generally be substituted for the innovator product. However, for some medicines, particularly those with a narrow therapeutic window, very small differences in the bioavailability of the active ingredient between the generic and the innovator product may have clinical implications in some patients.

Examples of medicines that require particular care when changing brands include lamotrigine and levothyroxine.

Lamotrigine

Lamotrigine has recently been the subject of a change in funding by PHARMAC³. The currently funded brand of lamotrigine (Logem) has been approved by Medsafe and shown to be bioequivalent to the innovator product (Lamictal).

Medsafe recommends that prescribers follow the UK Medicines and Healthcare products Regulatory Agency’s (MHRA) advice that brand switches for lamotrigine must be managed carefully with close patient monitoring, taking into account factors such as seizure frequency and treatment history⁴. The evidence that lamotrigine has a narrow therapeutic window is inconclusive at present. However, there is information to show that patients find changing brands difficult⁵.

Levothyroxine

Levothyroxine has a complex pharmacokinetic profile with a narrow therapeutic window and requires careful dose titration and monitoring⁶.

A change in formulation of the Eltroxin brand of levothyroxine in 2007 resulted in a large number of patients experiencing problems. Although the new formulation was bioequivalent to the original formulation, the problems experienced by patients highlighted the need for careful monitoring and dose titration with any change to this medicine^7,8.

Medsafe has approved three brands of levothyroxine: Eltroxin (50 mcg and 100 mcg tablets), Synthroid (25 mcg, 50 mcg and 100 mcg tablets) and Eutroxsig (50 mcg, 75 mcg, 100 mcg and 200 mcg tablets). Although both Synthroid and Eutroxsig are bioequivalent to Eltroxin, switching between brands should be avoided because even slight differences in bioavailability of levothyroxine may have a clinical effect. If a brand change is necessary (eg, because of intolerance to a particular product), the patient should be carefully monitored, and the dose titrated.

Levothyroxine (Mercury Pharma) tablets are marketed in New Zealand with provisional consent under section 23 of the Medicines Act 1981. Bioequivalence has not been demonstrated for this product.

Levothyroxine (Mercury Pharma) should only be prescribed for patients who are already taking this product and (1) are known to be intolerant to other available levothyroxine-containing products or (2) changing to another levothyroxine-containing product is not clinically appropriate⁹. New patients should not be started on Levothyroxine (Mercury Pharma).

Different brands can be combined when necessary

Using a combination of tablet strengths from different brands of a medicine to achieve a required dose is acceptable, but the patient should remain on the same brand of each strength tablet. Finding the correct dosage and combination should be based on clinical assessment and laboratory monitoring, where applicable.

More information

More information on generic medicines and bioequivalence is available in a previous edition of Prescriber Update.

You can search for medicine data sheets on the Medsafe website.

References

1. Medsafe. 2017. The Medsafe Files – Episode Four: New Medicines Assessment (Part 2). Prescriber Update 38(3): 43–4. URL: www.medsafe.govt.nz/profs/PUArticles/September2017/TheMedsafeFiles4NMAssessment.htm (accessed 29 October 2019).
2. bpac NZ. 2007. What is bioequivalence. Best Practice Journal SE: 12–16. URL: https://bpac.org.nz/BPJ/2007/March/bioequiv.aspx (accessed 29 October 2019).
3. PHARMAC. 2019. Lamotrigine: Logem is the new funded brand 15 October 2019. URL: www.pharmac.govt.nz/medicines/my-medicine-has-changed/lamotrigine-epilepsy-drug-changes/ (accessed 22 October 2019).
4. Medicines and Healthcare products Regulatory Agency. 2017. Antiepileptic drugs: updated advice on switching between different manufacturers’ products. Drug Safety Update 11(4): 5. URL: https://www.gov.uk/drug-safety-update/antiepileptic-drugs-updated-advice-on-switching-between-different-manufacturers-products (accessed 22 October 2019).
5. Epilepsy Society and Epilepsy Action. 2015. Patient experiences of switching between different versions of anti-epileptic drugs. URL: https://www.epilepsyresearch.org.uk/wp-content/uploads/2015/02/Patient-experiences-of-switching-between-different-versions-of-AEDs.pdf (accessed 8 November 2019).
6. Pharmacy Retailing (NZ) Limited. Eltroxin New Zealand Data Sheet 23 May 2019. URL: www.medsafe.govt.nz/profs/Datasheet/e/Eltroxin(new)tab.pdf (accessed 22 October 2019).
7. Medsafe. 2013. Eltroxin formulation change 4 July 2013. URL: www.medsafe.govt.nz/hot/alerts/ EltroxinInfo.asp (accessed 29 October 2019).
8. bpac NZ. 2007. Eltroxin (levothyroxine formulation change). Best Practice Journal 15: 48–51. URL: https://bpac.org.nz/BPJ/2008/August/eltroxin.aspx (accessed 29 October 2019).
9. Mercury Pharma (NZ). 2019. Levothyroxine New Zealand Data Sheet 13 September 2019. URL: www.medsafe.govt.nz/profs/Datasheet/ l/Levothyroxinetab.pdf (accessed 29 October 2019).