CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
296
AFRICA
Focus on 2010 South African Heart Congress
Dangers of switching anti-hypertension medication
Physicians should discourage switching
between anti-hypertension medications
and should encourage both the patient and
the funder to stick with the successfully
up-titrated medication.
‘There is always the concern that
by switching drugs, normally tolerated
confidence intervals of bioequivalence
studies may be compounded and result in
poor blood pressure control and increased
risk of suffering a cardiovascular or cere-
brovascular event in at-risk patients.’ This
view was presented in a very considered
manner by Prof Peter Meredith, reader in
clinical pharmacology at the University
of Glasgow, who attended and spoke at
the recent SA Heart Congress at Sun City.
‘In my view, while most generics are
quality products, the prescribing physi-
cian is entitled to get access to the rele-
vant bioequivalence data – this is not done
in the UK, Europe or the United States. At
minimum, the comparator agent against
which the generic has been shown to be
bioequivalent should be indicated in the
package insert.’
Evidence also suggests that it is quite
difficult to mimic the nifedipine gastroin-
testinal therapeutic system (GITS),
1,2
and
the UK formulary still cautions against
interchanging between nifedipine formu-
lations. ‘The British National formulary
states that different versions of modified-
release formulations may not have the
same clinical effect. To avoid confusion
between these different formulations of
nifedipine, prescribers should specify the
brand to be dispensed, Prof Meredith
pointed out.
Dr Meredith stressed that no other
modified-release preparation of nifed-
ipine has demonstrated evidence of
comparable clinical efficacy to nifedipine
GITS in clinical outcome studies. ‘In
my view also, none have demonstrated
definitive evidence of bioequivalence to
nifedipine GITS, as different bioequiva-
lence standards apply in different regions.
For example, in Europe, steady-state
bioequivalence is required for modified-
release (MR) formulations, whereas this
is not required for nifedipine MR formu-
lations in the United States. However the
FDA does require evidence of bioequiva-
lence of nifedipine in both the fasting and
fed situations, which is not a requirement
in Europe.’
Research in Europe on different
formulations
3-5
has shown resultant differ-
ences in bioequivalence data, which have
clinical implications for patient care, such
as lack of 24-hour blood pressure control
and the unnecessary addition of other
medications to achieve targeted blood
pressure levels. South African regulatory
agencies require comparative bioavail-
ability/bioequivalence studies as proof
of the efficacy of generic medicines
but published guidelines are silent with
regard to specific guidance concerning
slow-release medications.
‘While the availability of generic
medicines has played a major role in
reducing drug costs and extending access,
there are still far too many question-
able generics worldwide’, Dr Meredith
noted. ‘At a minimum, generic companies
should show efficacy in the target popula-
tion. Also, post-marketing surveillance of
some kind should be done by non-innova-
tor generic manufacturers as a contribu-
tion to self-inspection’, he concluded.
J Aalbers, Special Assignments Editor
1. Meredith PA. The unique Adalat story –
nifedipine gastrointestinal therapeutic
system.
Euro Cardiovasc Dis
2007;
1
: 1–7.
2. Meredith PA, Elliott HL. Dihydropyridine
calcium channel blockers: basic pharmaco-
logical similarities but fundamental thera-
peutic differences.
J Hypertens
2004;
22
:
1641–1648.
3. Schug BS, Brendel E, Wolf D,
et al
.
Formulation-dependent food effects demon-
strated for nifedipine modified-release prep-
arations marketed in the European Union.
Eur J Pharm Sci
2002;
15
(3): 279–285.
4. Schug BS, Brendel E, Wonnemann M,
et
al
. Dosage form-related food interaction
observed in a marketed once-daily nifed-
ipine formulation after a high-fat American
breakfast.
Eur J Clin Pharmacol
2002;
58
(2):
119–125.
5. Wonnemann M, Schug, Schmucker K,
et al
.
Significant food interations observed with
nifedipine modified-release formulation
marketing in the European Union.
Int J Clin
Pharmacol Ther
2006;
44
(1): 38–48.
