Website: October 2004
Prescriber Update 2004;25(2):23-24
Medsafe Editorial Team
Prescribers are advised to be on the look out for signs
of toxicity in patients taking anticonvulsants or warfarin who concurrently
receive influenza vaccination.
Carbamazepine, warfarin and other
medicines reported to interact with the influenza vaccine
No clear mechanism of action but hepatic enzymes may be
Prescribers and patients should be alert for signs of
Carbamazepine, warfarin and
other medicines reported to interact with the influenza vaccine
In recent years, New Zealand public health campaigns to encourage prophylaxis
with influenza vaccines (Fluarix™,
Vaxigrip™) have targeted patient groups who are most at risk from
influenza virus infection, such as people over 65 years of age or those with
chronic diseases that impair infection response.1
The target group include patients taking a number of medicines.
Reports of patients developing phenytoin, warfarin or
theophylline toxicity following influenza vaccination have been published.2-5
In one study, toxic elevations in levels of the concurrent medicines were
reported to occur up to 28 days post-vaccination.5
Other cases of possible interactions include:
No clear mechanism of action but
hepatic enzymes may be involved
The mechanism of action for these interactions is suspected to involve
cytochrome P450 3A4 hepatic enzyme inhibition, leading to reduced clearance
of the concurrently administered medicine.* However, not all published cases
support this explanation;4 for example, the
interaction between warfarin and the influenza vaccine is thought to more
likely involve an alteration in the synthesis of blood clotting factors.7
While increasing age may be a risk factor for enzyme
inhibition by the influenza vaccine, overall, the potential for interaction
has high inter-individual variability.8 The
effectiveness of the influenza vaccine is not thought to be affected.
Prescribers and patients
should be alert for signs of toxicity
In general, influenza vaccines are not associated with clinically significant
interactions. However, these case reports highlight the possibility that the
influenza vaccine may interact with some concurrent medicines, particularly
those with a narrow therapeutic index.
Prescribers are asked to look for signs of toxicity with
any of the medicines metabolised by cytochrome P450 3A4 in patients who are
co-administered an influenza vaccine. Increased monitoring of anticoagulant
therapy is recommended. Inform patients of signs of toxicity, particularly
for anticonvulsants where frequent monitoring is not likely to be practical.
In all instances, ask patients to report symptoms immediately to their
doctor. If toxicity is suspected, check appropriate blood levels.
The possible risk of interactions should not preclude
patients from being administered an influenza vaccine. Any suspected
vaccine-medicine interactions should be reported to CARM in Dunedin (see
inside back cover for details).
* Medicines affected by the cytochrome P450 3A4 enzyme
include carbamazepine, warfarin, statins, phenytoin, ketoconazole,
theophylline, cisapride, calcium-channel antagonists, protease inhibitors,
benzodiazepines and some tricyclic antidepressants.6
Competing interests (authors): none declared.
Ministry of Health. Recommended
immunisation schedule. Immunisation Handbook 2002; Wellington,
p.184. Available as a PDF on the Ministry of Health web site:
Poli D, Chiarugi L, Capanni M, et al.
Need of more frequent International Normalized Ratio monitoring in elderly
patients on long-term anticoagulant therapy after influenza vaccination.
Blood Coagul Fibribolysis 2002;13:297-300.
Robertson WC. Carbamazepine toxicity
after influenza vaccination. Pediatr Neurol 2002;26:61-63.
Meredith CG, Christian CD, Johnson RF,
et al. Effects of influenza virus vaccine on hepatic drug metabolism.
Clin Pharmacol Ther 1985;37:396-401.
Jann MW, Fidone GS. Effect of influenza
vaccine on serum anticonvulsant concentrations. Clin Pharm
Cupp MJ, Tracy TS. Cytochrome P450: New
nomenclature and clinical implications. Am Family Physician
Stockley IH (Ed). Stockley's Drug
Interactions 6th edn. London: Pharmaceutical Press, 2002.
Hayney M, Buck J. Effect of age and
degree of immune activation on cytochrome P450 3A4 after influenza
immunization. Pharmacotherapy 2002;22:1235-1238.
From The TimesNovember 24, 2007
Flu jab not reliable, says its inventor
CANBERRA The inventor of the flu vaccination, which is given to 15 million
Britons each year, said that he feared a severe outbreak of the virus and that
he had never been very impressed with its efficacy.
Dr Graeme Laver, former Professor of Biochemistry at the Australian National
University in Canberra, said: “It is better to do nothing, and I wouldn’t want
to advise people not to take it, but you can’t rely on it doing any good.”
Instead, Dr Laver said the best way to protect public health was to make drugs
that fight the virus after infection — such as Tamiflu and Relenza, —
available over the counter. He said that as they are available only by
prescription, valuable time is lost as people wait to see their GPs.
Dr Laver, who receives royalties from the sale of Relenza, told the Daily
Mail: “You could have a severe epidemic. Thousands will be ill and many will
die. Doesn’t anyone care? The safe and effective anti-flu drugs could, if used
correctly, avoid much of this distress.”