• Reducing consumer confusion
• GP influence on acceptance
• Pharmacists’ role
• Affordability of generic medicines

Generic medicines:
dealing with multiple brands

More often, consumers are being presented with the choice of a generic medicine because of increases in the number of generic medicines available, increased awareness about generic medicines and government strategies to enhance uptake. Generic medicines help spread the healthcare dollar, but some health professionals and consumers have reservations about using them. This NPS News considers some of the issues around generic medicines and brand substitution, and how health professionals can help consumers use generic medicines safely and appropriately.

Generic medicines are bioequivalent

"I don’t prescribe generic medicines because I don’t believe that they’re all equivalent …” [GP][1]

"One can’t help but wonder whether you are getting an inferior medication with generics” [Consumer][2]

Two products are considered bioequivalent when they produce similar plasma concentrations of the same active ingredient. Bioequivalence is usually assessed in healthy volunteers by administering the two products on separate occasions. The peak plasma concentration (C_max) and the extent of absorption (area under the concentration–time curve, AUC) of the generic medicine and the original brand are compared. To be bioequivalent, the 90% confidence intervals (CI) for the ratio of each pharmacokinetic variable must lie between 0.80 and 1.25. This is a numerical index that provides an indication of the certainty of the study results. It does not mean that the C_max and AUC ratios can vary by –20 to +25%.[3] In practice, the differences in the pharmacokinetic variables of the two products would have to be less than 10% to satisfy the 90% CI bioequivalence requirement.[3] The amount of active ingredient in the systemic circulation (bioavailability) is taken as a measure of the product’s clinical efficacy.[4]

Bioequivalence between the original brand and the generic version of a medicine is the fundamental basis of generic substitution. However, in a survey of Australian GPs (N = 785) 27% believed that generic medicines are not always as effective as branded medicines and 30% were undecided about their bioequivalence.[5] Although there may be exceptions (e.g. medicines with narrow therapeutic indices), this lack of confidence in generic medicines is largely unfounded physiologically. For a generic medicine to be listed on the Pharmaceutical Benefits Scheme (PBS), a manufacturer/supplier must demonstrate that their product is bioequivalent to the original brand available in Australia.[6] Generic medicines must also adhere to the same quality of manufacturing codes as branded medicines.[7]

Inactive ingredients (e.g. binders and fillers) may differ between bioequivalent products. However, adverse reactions to inactive ingredients are rare.

Education minimises confusion

The most common concern with brand substitution, shared by GPs and pharmacists alike, is consumer confusion — particularly among the elderly.[5,8,9] The concern is that confusion may lead to double dosing or reduced adherence.[10] Confusion can also arise when consumers receive a generic medicine in hospital or when travelling.

In the pharmacy

Pharmacists can use Label 15, which states “This medicine replaces … Do not use both”, on the container whenever the brand is changed. Explain to the consumer when a medicine is being replaced with an alternative brand and draw their attention to Label 15. Advise them not to start the new pack until they have finished the previous pack.

Pharmacists should also explain any differences in appearance or form (e.g. colour, tablet vs capsule) and ensure the active ingredients appear prominently on pharmacy labels.

Pharmacy assistants should be educated about potential consumer confusion (particularly in the elderly) and how to avoid it (see Counter Connections, inPharmation 2007;11(8): December special edition).

The pharmacy should also implement a brand substitution policy that should consider:

• when brand substitution will be offered
• obtaining consumer consent
• recording consumer brand substitution preferences
• brand consistency
• addressing consumer requests for brand substitution that go against the stated intention of the prescriber.[11]

An additional concern for some GPs is the possibility that multiple generic brands may be substituted during the life of a prescription.[12] A recent study of 533,279 prescriptions for 8 medicines for chronic conditions commonly dispensed on the Repatriation Pharmaceutical Benefits Scheme (RPBS) found that substitution occurred in only 7% of cases and only 1% had more than one substitution.[13] The findings of this study may not directly apply to the general population or for all types of medicines. However, it suggests that pharmacists are generally consistent in the selection of brands for consumers on long-term therapy, in accordance with their professional code.[13,14]

GPs can influence consumer choice

“I believe in sticking to what I’ve been prescribed before. I know the doctor and I feel safe with his choice of medication.” [Consumer] [15]

Health professionals, especially GPs, can have a strong influence on consumer acceptance of generic medicines. In a consumer survey (n = 310), 50% indicated they would not use a generic medicine without checking with their GP despite agreeing that the generic medicine contained the same ingredients as the branded medicine.[16]

Figure 1: Online PBS Schedule for health professionals (www.pbs.gov.au).

(Copyright Commonwealth of Australia; reproduced with permission)

http://www.pbs.gov.au/html/healthpro/search/results?term=atenolol&scope=PBS+STATIC&form-type=simple

Pharmacists’ role

A survey of 443 consumers taking medicines for chronic conditions showed that 79% trusted pharmacists’ recommendations. Pharmacists play an important role in educating consumers about the efficacy and safety of generic medicines. Acceptance of generic medicines has been shown to be influenced by satisfaction with the communication and quality of information consumers receive from health professionals.[17,18]

Affordability of generic medicines

“It’s more based on cost factors because, you know, I have a lot of medication, so I’m trying to reduce my medication cost.” [Consumer] [15]

For the individual

A consumer’s ability to pay for medicines can influence adherence.[10,19] Using generic medicines is one way consumers can minimise the cost of their medicines, particularly if they are using multiple medications for chronic conditions.

For the community

Extensive reforms were introduced to the PBS from 1 August 2007. The main aim of the reforms is to encourage competition within the medicines industry and thereby enable the PBS to get the most value for money.[20] Paying less for medicines that no longer have a patent allows the government to subsidise newer, more expensive medicines on the PBS (e.g. rituximab: $2309 for a 500 mg vial).

There are financial considerations for pharmacists associated with dispensing and supplying generic medicines. A payment of $1.50 per generic prescription will compensate pharmacists (from 1 August 2008) under the new PBS arrangements. However, the guiding principle in any brand substitution decision, as endorsed by the Pharmaceutical Society of Australia, is that the consumer’s health should always be the pharmacist’s prime consideration and that brand substitution should not place consumers at risk.[14]

When is brand substitution not appropriate?

• Consumers with clinically significant intolerances to inactive ingredients included in the generic medicine (e.g. lactose, gluten, colours). Inactive ingredients may also be important for those who observe particular religious or cultural practices. Ingredients are listed at the end of the consumer medicine information (CMI) and at the beginning of the product information (PI) for each medicine.
• Consumers who are more likely to become confused (e.g. cognitive or vision impairment, non-English speaking background).
• Critical dose or narrow therapeutic index medicines (i.e. medicines for which relatively small variations in plasma concentrations can cause significant adverse effects or loss of efficacy). Examples include cyclosporin, digoxin and warfarin.
• Conditions in which negative perceptions/attitudes to substitution can impact on treatment adherence or response (e.g. people with mental illnesses).

Useful Resources

Schedule of Pharmaceutical Benefits (www.pbs.gov.au) – online version for health professionals shows approximate price for consumers of all available brands and indicates whether brand premiums apply. CMIs and PIs are also available for some medicines.

Counter Connections, inPharmation 2007; 11(8): December special edition – pharmacy assistants module, addresses how pharmacy assistants can help consumers avoid confusion.

Medicines Talk: Generic medicines explained. August 2007. (Go to www.nps.org.au/consumers) – contains examples of pharmacy labels for branded and generic medicines.

Fact Sheet: Generic medicines. July 2007. (PDF document 83 kB)

Consumer medicine information leaflets (www.nps.org.au/consumers)

Expert reviewer

Dr John De Vries, GP, Indooroopilly QLD
Dr David Gleave, GP, Jandakot WA

Reviewers

Dr James Best, GP
A/Prof Nick Buckley, Clinical Pharmacologist, The Canberra Hospital
Ms Jan Donovan, Consumer
Dr John Dowden, Editor, Australian Prescriber
Ms Debbie Norton, Pharmacist
Ms Susan Parker, Head of Medical Affairs, Pfizer Australia
Ms Simone Rossi, Editor, Australian Medicines Handbook

Any correspondence regarding content should be directed to NPS. Declarations of conflicts of interest have been sought from all reviewers.

References

1. Hassali MA, Kong DCM, Stewart K. Generic medicines: Perceptions of general practitioners in Melbourne, Australia. J Generic Med 2006;3:214-25.
2. Eureka Strategic Research. Community quality use of medicine program for people with chronic conditions: Unpublished report commissioned by the National Prescribing Service, 2006
3. Pearce GA, McLachlan AJ, Ramzam I. Bioequivalence: How, why, and what does it really mean? J Pharm Pract Res 2004;34:195-200.
4. Borgheini G. The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clin Ther 2003;25:1578-92.
5. National Prescribing Service. National General Practitioner Survey: National Prescribing Service, 2006.
6. Therapeutic Goods Administration. Australian Regulatory Guidelines for Prescription Medicines. Appendix 15: Biopharmaceutics Studies. Canberra: TGA, 2004. (accessed 19 September 2007).
7. Therapeutic Goods Administration. Good manufacturing practice for therapeutic goods. Canberra: TGA, 2003. (accessed 19 September 2007).
8. National Prescribing Service. National Pharmacist Survey: National Prescribing Service, 2006.
9. Hassali MA, Kong DCM, Stewart K. Generic medicines: Perceptions of community pharmacists in Melbourne, Australia. J Pharm Fin Econ Policy 2005;14:27-45.
10. Pharmaceutical Health and Rational Use of Medicines Committee. Consumer perspectives on managing multiple medicines. Canberra: PHARM, 2001.
11. Pharmacy Guild of Australia. Quality Care Pharmacy Program: 2000 Brand Substitution Policy P2B: Pharmacy Guild of Australia, 2000.
12. Australian Divisions of General Practice. GPs call for "One switch per script". 2003. (accessed 20 September 2007).
13. Kalisch LM, Roughead EE, Gilbert AL. Pharmaceutical brand substitution in Australia--are there multiple switches per prescription? Aust N Z J Public Health 2007;31:348-52.
14. Pharmaceutical Society of Australia. Guidelines for pharmacists on PBS brand substitution. 2004.
15. Hassali MA, Kong DCM, Stewart K. Generic medicines: perceptions of consumers in Melbourne, Australia. Int J Pharm Pract 2005;13:257-64.
16. Stancombe Research and Planning. Consumer tracking research: Changes in generic medicine usage and attitudes. Sydney: Stancombe Research and Planning, 2005.
17. Valles JA, Barreiro M, Cereza G, et al. A prospective multicenter study of the effect of patient education on acceptability of generic prescribing in general practice. Health Policy 2003;65:269-75.
18. Dowell JS, Snadden D, Dunbar JA. Changing to generic formulary: how one fundholding practice reduced prescribing costs. BMJ 1995;310:505-8.
19. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487-97.
20. Department of Health and Ageing. Senate Community Affairs Committee inquiry into: National Health Amendment (Pharmaceutical Benefits Scheme) Bill 2007. Department of Health and Ageing, 2007.
21. Pharmaceutical Benefits Pricing Authority. Annual report for the year ended June 2006. Canberra: PBPA, 2006.