Prescrire International Special Edition 2015/Volume 24 N°158
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Translated from
Rev Prescrire
November 2014;
34 (373): 827
Lamotrigine: nightmares
Dose-dependent.
I
n February 2014, the
Netherlands Pharmacovigi-
lance Centre, Lareb, repor-
ted 3 cases of nightmares
and one case of abnormal dreams in
patients taking lamotrigine, an antiepilep-
tic drug used in certain forms of epilepsy
and in bipolar disorder (1). The nightmares
diminished or disappeared after lamotri-
gine discontinuation or dose reduction.
In late 2013, the pharmacovigilance
database of the World Health Orga-
nization (WHO) at Uppsala contained
107 reports of nightmares and 75 reports
of abnormal dreams associated with
the use of lamotrigine. The European
pharmacovigilance database (Eudra-
vigilance) contained 35 cases and
13 cases, respectively (1).
Many factors can provoke nightmares,
including drugs, in particular psychotropic
agents or drugs used to treat neurologi-
cal disorders (2). The role of lamotrigine
should be suspected if the onset of recur-
rent nightmares coincides with the start
of exposure.
©Prescrire
Selected references from Prescrire’s literature
search.
1-
Lareb “Lamotrigine and nightmares” 20 Feb-
ruary 2014.
accessed 21 May 2014:
9-13.
2-
Prescrire Editorial Staff “Drug-induced night-
mares”
Prescrire Int
2000;
9
(50): 181-182.
Translated from
Rev Prescrire
November 2014;
34 (373): 827
Pazopanib:
retinal detachment
Patients should be informed.
P
azopanib is an oral in-
hibitor of multiple tyrosine
kinases, including those
associated with the vas-
cular endothelial growth factor (VEGF)
receptor (1).
In January 2014, the European Med-
icines Agency (EMA) reported an ana-
lysis of 12 cases of retinal detachment
and retinal tear retrieved from the UK
pharmacovigilance database (2). The
timing of the onset of the lesions suggest-
ed a link with exposure to oral pazopanib.
Retinal detachment has been observed
with aflibercept, pegaptanib, ranibizumab
and bevacizumab, which also inhibit VEGF
and are administered intraocularly (3).
It is better to advise patients taking
pazopanib to visit a doctor promptly if
they develop visual disturbances. This
advice should probably also be given to
patients taking a VEGF inhibitor.
©Prescrire
Selected references from Prescrire’s literature
search.
1-
Prescrire Editorial Staff “Pazopanib. Kidney can-
cer: many risks, but is there a benefit for patients?”
Prescrire Int
2011;
20
(114): 64-66.
2-
EMA“Pharmacovigilanceriskassessmentcommit-
tee (PRAC) Minutes of the meeting on 6-9 January
2014.4-1-5Pazopanib-Votrient°”6February2014.
accessed 25 May 2014: 15.
3-
“Pazopanib hydrochloride”. In: “Martindale
The Complete Drug Reference” The Pharmaceuti-
cal Press, London.
accessed 26 May 2014: 5 pages.
Translated from
Rev Prescrire
July 2014; 34
(369): 511
Cefepime: serious
neurological adverse
effects
Renal impairment is a risk factor.
S
ince theearly 2000s, neuro-
toxicity has been reported
in patients treated with cefe-
pime (1). This problem was
confirmed in mid-2014 by the European
Medicines Agency (EMA) (2).
Cefepime is an injectable broad-
spectrum beta-lactam antibiotic of the
cephalosporin class that appears to
have greater efficacy against certain
bacteria than “third generation” cephalo-
sporins (3). Convulsions and enceph-
alopathy are known adverse effects of
beta-lactam antibiotics (1).
In 2013, a US team published a retro-
spective study based on the medical
records of 100 intensive care patients
(average age 66 years) treated with
cefepime for a median duration of
6 days. The study population included
84 patients with chronic or acute renal
failure, 33 of whom were undergoing dia-
lysis. Fifteen patients developed various
neurological adverse effects attributed
to cefepime: impaired consciousness
(13 cases), myoclonus (11 cases), dis-
orientation (6 cases) and nonconvulsive
status epilepticus (1 case) (4). The main
risk factors were renal impairment and
failure to correctly adjust the dose of
cefepime for renal function (4).
Another team retrospectively com-
pared 183 patients treated with cefepime
and 745 patients treated with the inject-
able beta-lactam antibiotic meropenem.
The frequency of convulsions was higher
in the cefepime group (statistically signif-
icant difference). All of the patients who
experienced convulsions with cefepime
had a history of neurological disorders,
but none had renal failure (5).
In 2012, the US Food and Drug Admin-
istration reported 59 cases of noncon-
vulsive status epilepticus in patients tak-
ing cefepime. In 43 cases, the patients
recovered, but 16 patients died, 13 from
other causes. Renal failure was pres-
ent in 58 patients, 56 of whom had not
received an appropriate dose adjustment
of cefepime (6).
The neurotoxicity of cefepime must be
taken into account. In the rare cases in
which cefepime’s antibacterial spectrum
justifies choosing it over other antibiot-
ics, the dose must be precisely adjusted
according to renal function, and patients
with a history of neurological disorders
must be carefully monitored.
©Prescrire
Selected references from Prescrire’s literature
search.
1-
“Cefepime hydrochloride”, “Benzylpenicillin”.
In: “Martindale The Complete Drug Reference”
accessed 3 June 2014: 7 pages.
2
- EMA “Pharmacovigilance Risk Assessment
Committee (PRAC) Minutes of the meeting on
3-6 March 2014. 4-1-1 Cefepime (NAP) - Signal
of convulsions” 10 April 2014: 14-15.
3-
Prescrire Rédaction “Céfépime: surcroît demor-
talité”
Rev Prescrire
2008;
28
(294): 274.
4-
Fugate JE et al. “Cefepime neurotoxicity in
the intensive care unit: a cause of severe, under-
appreciated encephalopathy”
Crit Care
2013; (6)
17
: R264.
5-
Tanaka A et al. “Comparison of the prevalence
of convulsions associated with the use of cefepime
and meropenem”
Int J Clin Pharm
2013;
35
(5):
683-687.
6-
USFDADrug SafetyCommunication “Cefepime
and risk of seizure in patients not receiving dos-
age adjustments for kidney impairment” 26 June
2012: 2 pages.
Prescrire Int • January 2015
Prescrire Int • January 2015
Prescrire Int • January 2015
