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Unexpected side effects with generic abacavir – and potential for rare reactions to other generic ARVs

May 24, 2017

Several anecdotal reports of mouth ulcers have recently been reported in people switching to generic abacavir in the UK. [1]

This should highlight awareness of the potential of likely-rare new side effects, even when both formulations have been approved as bioequivalent.

These are likely to be very uncommon reactions, but given they are currently unexpected, it is important to consider new symptoms following a switch to generic formulations. It is also important during the early months of using generics that such symptoms are reported to the UK yellow card scheme. [2]

Background

As many widely used HIV medicines reach the end of patents, the move to generic formulations will save the NHS millions of pounds each year.

Generic medicines used in the UK as just as carefully monitored as original formulations. Generics have proven to have the same pharmacokinetic properties as original formulations with comparable drug levels of the active ingredients. However, some generics medicines are manufactured slightly differently, using different non-active ingredients in medicines – called excipients – and also sometimes using a slightly different base compound. [3]

Both abacavir and tenofovir are now available as generics in the UK, using slightly different base compounds. This is partly to overcome restrictions linked to the original patents. Other generic ARVs including lamivudine, nevirapine and efavirenz start use the same base formulations as the original drugs.

Abacavir/lamivudine

Three manufacturers now provide generic versions of Kivexa, the dual nucleoside single pill containing abacavir and lamivudine manufactured by ViiV Healthcare. Although a patent extension still exists for Kivexa, ViiV Healthcare are not challenging or enforcing this.

The two generic formulations manufactured by Lupin and Mylan, both use a base salt of abacavir hydrochloride, compared to an abacavir sulphate base in Kivexa. The generic formulation manufactured by Teva is present as a free base. All three formulations have proven to be similar in terms of active ingredients.

Although the generic formulations have different packaging, all three formulations are similar size, shape and orange to the Kivexa.

Tenofovir DF/emtricitabine

Although generic versions of Gilead’s Truvada (tenofovir DF/emtricitabine) are not currently available in the UK, this is expected to change in the summer 2017, with several generic manufacturers likely to launch so-called “at-risk” generic formulations (as they might be challenged by Gilead).

Many of the generic formulations used outside the UK use a different tenofovir base tenofovir disoproxil maleate (TDM) rather than tenofovir disoproxil fumerate (TDF) used in the orginator drug. The active drug is the same from all formulations.

Nevirapine

The UK generic version of Boehringer Ingelheim’s version of nevirapine (Viramune) is currently manufactured by Teva.

Both versions are once-daily extended release formulations, with similar shape, size and are off-white.

COMMENT

The association between these events and the switch to generics is not clear.

Even if they are related, this is likely to be a rare event since switching to generics is standard practice with all medicines provided by the NHS when patents have expired and cheaper alternatives exist. These reports should not deter people from switching to generics.

However, anybody who develops similar symptoms that do not resolve swiftly should contact their healthcare provider taking note of the brand of generic as well as the batch number.

The suspected reactions to generic abacavir were first reported at a meeting of the NHS CRG drugs group. They included one case of persistent and worsening mouth ulcers that developed for several weeks after switching from Kivexa. The symptoms in this case improved within one day of switching back to originator formulation.

Case details are currently being collected, including the generic brand and batch number, for a detailed report.

Other cases should be reported to both the yellow card scheme and the CRG drug group. [2, 4]

The vast majority of the 17 million HIV positive people globally are effectively treated with generic medicines with no currently reported differences compared to the originator product.

However, single cases of reactions to different excipients for other medicines have occasionally been reported.

  • An allergic reaction to croscarmellose sodium used as excipient in a generic furosemide preparation in a patient who had previously been taking branded furosemide. [5]
  • GI disturbance in lactose-intolerant patient with an arrhythmia who was switched from one formulation of antiarrhythmic drug (e.g., Isoptin 120 mg or Rytmonorm 300 mg) to another that contains a lactose-based excipient (e.g., Verapamil or Propafenone Sandoz).

The originator versions of HIV drugs will still be available for rare cases of reactions to generic formulations.

References

  1. CRG Drug Group, (11 May 2017).
  2. MHRA yellow card scheme.https://yellowcard.mhra.gov.uk
  3. NHS Specialist Pharmacy Service. New generics antiretroviral product (2016).https://www.sps.nhs.uk/articles/new-generic-antiretrovirals-products-2016
  4. CRG Drug group can be contacted by emailing the HIV CRG lead commissioner. <janette.harper@nhs.net>
  5. Mumoli N et al. An allergic reaction to croscarmellose sodium used as excipient in a generic drug, QJM. 2011;104:709–10.

Source: i-base.info