Drug-induced vertigo


Dizziness is a complaint frequently encountered in general practice. In practice it is difficult to distinguish between sensations referred to as dizziness and vertigo, that is, dizziness caused by vestibular dysfunction. Vertigo can be triggered by changes of posture or position, and is characterised by a feeling that the head is rotating or oscillating. The dizziness may be accompanied by other symptoms, such as nausea and vomiting, tinnitus, balance problems and falls. A vestibular cause is likely if nystagmus is present. The form most commonly seen in practice is benign paroxismal positional vertigo (BPPV).
Patient information leaflets for many drugs mention dizziness or vertigo as a possible side-effect. The present article outlines the research evidence on drug-induced vertigo. Only a few drugs are known to sometimes cause vertigo; it is a rare side-effect. In such cases the vertigo is not an isolated symptom, but is often accompanied by nausea, vomiting or otic symptoms. The data on this subject generally come from studies with a low evidence level. In many cases, it is unclear whether the diagnosis was confirmed by supplementary examination, and information on the course of the disease and possible reversibility are lacking. In addition, the terminology is not always used consistently. This is particularly true for reports submitted to adverse effects reporting centres.
Aminoglycosides have long been known to be ototoxic and may also be vestibulotoxic. There has, however, been little high-quality research into this side-effect. Published work largely consists of small randomised studies, case series and anecdotal reports, although these publications do report the use of supplementary examinations to conform vertigo. The available evidence for vertigo caused by antimalaria drugs, especially mefloquine, is also low-level. Meta-analyses of randomised studies have shown that the anti-epileptics pregabalin and lacosamide cause vertigo more often than placebo, but it is not clear whether these cases concerned actual vertigo or another form of dizziness. In addition, the included studies were not designed to test differences in side-effects. A database operated by the American Food and Drug Administration (FDA) has provided evidence that α-blockers can also cause vertigo. In view of their pharmacological characteristics, however, it seems more likely that these drugs cause orthostatic hypotension.
The important message for routine practice is that if a patient presents with symptoms of vertigo, drugs should be included in the differential diagnosis as a possible cause. If it seems likely to be a side-effect, for instance if the symptom subsides after the suspected drug is discontinued (dechallenge) and returns when the drug is reinstated (rechallenge), the doctor might consider trying a different drug. Other and future users will benefit if doctors, pharmacists and patients report suspected side-effects as accurately as possible, that is, including information about the possible temporal relationship, co-medication and other possible causes.

References*

  1. Linden MW van der, Westert GP, Bakker DH de, Schellevis FG. Tweede nationale studie naar ziekten en verrichtingen in de huisartsenpraktijk. Klachten en aandoeningen in de bevolking en in de huisartspraktijk. Utrecht/Bilthoven: NIVEL/RIVM, 2004.
  2. Incidentie- en prevalentiecijfers in de huisartsenpraktijk [internet]. Nederlands instituut voor onderzoek van de gezondheidszorg (NIVEL). Via: http://www.nivel.nl/en/node/1674.
  3. Verheij AAA, Weert HCPM van, Lubbers WJ, Sluisveld ILL van, Saes GAF, Eizenga WH, et al. NHG-Standaard ’Duizeligheid’. Huisarts Wet 2002; 45: 601-609.
  4. Huizing EH, Snow GB (red.). Leerboek keel-, neus- en oorheelkunde. Houten: Bohn Stafleu van Loghum, 2005.
  5. Kuks JBM, Snoek JW (red.). Klinische neurologie. Houten: Bohn Stafleu van Loghum, 2012.
  6. Debruyne F, Marres H (red.). Zakboek keel-, neus-, oorheelkunde. Leuven: Acco, 2011.
  7. Bijwerkingendatabank, via: www.lareb.nl, bijwerkingen.
  8. Informatorium Medicamentorum. Den Haag: KNMP, 2015.
  9. Antibiotica gebruik in Nederland [document op het internet]. Stichting Werkgroep Antibioticabeleid. Via: https://www2.sfk.nl/producten/swab/landelijk.
  10. Bitner-Glindzicz M, Rahman S. Ototoxicity caused by aminoglycosides. BMJ. 2007; 335: 784-785.
  11. Aronson JK [ed.]. Meyler’s side effects of antimicrobial drugs. Amsterdam: Elsevier, 2010.
  12. Nakashima T, Teranishi M, Hibi T, Kobayashi M, Umemura M. Vestibular and cochlear toxicity of aminoglycosides--a review. Acta Otolaryngol 2000; 120: 904-911.
  13. Troost BT. Dizziness and vertigo in vertebrobasilar disease. Part 1: peripheral and systemic causes dizziness. Stroke 1980; 11: 301-303.
  14. Productinformatie amikacine (merkloos), via: www.cbg-meb.nl, Geneesmiddeleninformatiebank.
  15. Productinformatie gentamicine (merkloos), via: www.cbg-meb.nl, Geneesmiddeleninformatiebank.
  16. Productinformatie tobramycine (merkloos), via: www.cbg-meb.nl, Geneesmiddeleninformatiebank.
  17. Crawford J. Living without a balancing mechanism. Br J Ophthalmol 1964; 48: 357-360.
  18. Ariano RE, Zelenitsky SA, Kassum DA. Aminoglycoside-induced vestibular injury: maintaining a sense of balance. Ann Pharmacother 2008; 42: 1282-1289.
  19. Lerner SA, Seligsohn R, Matz GJ. Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin. Am J Med 1977 ; 62: 919-923.
  20. Nordström L, Ringberg H, Cronberg S, Tjernström O, Walder M. Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity? J Antimicrob Chemother 1990; 25: 159-173.
  21. Scheenstra RJ, Rijntjes E, Tavy DL, Kingma H, Heijerman HG. Vestibulotoxicity as a consequence of systemically administered tobramycin in cystic fibrosis patients. Acta Otolaryngol 2009; 129: 4-7.
  22. Bath AP, Walsh RM, Bance ML, Rutka JA. Ototoxicity of topical gentamicin preparations. Laryngoscope 1999; 109: 1088-1093.
  23. Tseng AL, Dolovich L, Salit IE. Azithromycin-related ototoxicity in patients infected with human immunodeficiency virus. Clin Infect Dis 1997; 24: 76-77.
  24. Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia 2011; 52: 826-836.
  25. GIPdatabank. Zorginstituut Nederland, via: www.gipdatabank.nl.
  26. Toename anti-epileptica [document op het internet]. Stichting Farmaceutische Kengetallen (SFK). Via: https://www.sfk.nl/nieuws-publicaties/PW/2014/toename-anti-epileptica.
  27. Productinformatie pregabaline (Lyrica®), via: www.cbg-meb.nl, Geneesmiddeleninformatiebank.
  28. Zaccara G, Perucca P, Loiacono G, Giovannelli F, Verrotti A. The adverse event profile of lacosamide: a systematic review and meta-analysis of randomized controlled trials. Epilepsia 2013; 54: 66-74.
  29. Riemsdijk MM van, Klauw MM van der, Heest JA van, Reedeker FR, Ligthelm RJ, Herings RM, et al. Neuro-psychiatric effects of antimalarials. Eur J Clin Pharmacol 1997; 52: 1-6.
  30. Yoshimura K, Kadoyama K, Sakaeda T, Sugino Y, Ogawa O, Okuno Y. A survey of the FAERS database concerning the adverse event profiles of α1-adrenoreceptor blockers for lower urinary tract symptoms. Int J Med Sci 2013; 10: 864-869.
  31. Arbusow V, Strupp M, Brandt T. Amiodarone-induced severe prolonged head-positional vertigo and vomiting. Neurology 1998; 51: 917.
  32. Schaefer SD, Wright CG, Post JD, Frenkel EP. Cis-platinum vestibular toxicity. Cancer 1981; 47: 857-859.
  33. Goundrey J. Vertigo after epidural morphine. Can J Anaesth 1990; 37: 804-805.
  34. Linder S, Borgeat A, Biollaz J. Meniere-like syndrome following epidural morphine analgesia. Anesthesiology 1989; 71: 782-783.
  35. Reid IR, Mills DA, Wattie DJ. Ototoxicity associated with intravenous bisphosphonate administration. Calcif Tissue Int 1995; 56: 584-585.

*The literature refers to the Dutch text