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Acute overdose due to benzydamine Lilian Gómez-López, José Hernández-Rodrîguez, Jordi Pou and Santiago Nogué Hum Exp Toxicol 1999; 18; 471 DOI: 10.1191/096032799678840264 The online version of this article can be found at: http://het.sagepub.com/cgi/content/abstract/18/7/471

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Case report

Acute overdose due to benzydamine Lilian GoÂmez-LoÂpez1, Jose HernaÂndez-RodrõÂguez2, Jordi Pou1 and Santiago NogueÂ*,2 1

Department of Pediatrics, Hospital Sant Joan de DeÂu-Hospital ClõÂnic, School of Medicine, University of Barcelona, Spain; 2Department of Internal Medicine, Clinical Toxicology Unit, Hospital ClõÂ nic, School of Medicine, University of Barcelona, Spain Benzydamine is a nonsteroidal anti-in¯ammatory drug, currently available as mouthwash, aerosol, dermal cream, vaginal douche preparation, pills and otic drops. Up to now no cases of poisoning due to this drug have been reported. A 6-year-old girl with an accidental poisoning with benzydamine is described. The episode consisted of

hallucinosis without other symptoms and resolved spontaneously in 17 h. Keywords: benzydamine poisoning; NSAID overdose; hallucinosis

Introduction Poisoning due to nonsteroidal anti-in¯ammatory drugs (NSAIDs) is rarely seen in childhood. Benzydamine belongs to this group of drugs and is available in mouthwash, dermal cream, aerosol and vaginal douche preparations, besides other compounds administered orally or by otic drops. Table 1 shows the proprietary names of benzydamine preparations and the countries where they are marketed. Up to now no cases of poisoning due to this drug have been published (Medline search using NCBI PubMed). We report the case of a girl who suffered from an accidental benzydamine overdose due to ingestion of a topical preparation.

patient was asymptomatic 3 h after the admission. Physical examination revealed a good clinical condition without any cutaneous or mucous abnormality. Temperature, blood pressure, cardiac and respiratory frequency were normal. Neurologic examination showed a normal alert consciousness

Table 1 Proprietary and multi-ingredient names of benzydamine preparations and the countries where they are marketed Country

Proprietary preparations

Multi-ingredient preparations

Austria Australia

Tantum Dif¯am

Canada France Germany Italy

Tantum Opalgyne Tantum A¯oben Benzirin Flogaton Ginesal Multum Sani¯or Dentifricio Sani¯or Vena Tantum Verax Tantum Andolex Tantum Fulgium Rosalgin Tantum

± Multi Anti-In¯ammatory Cough Lozenges Dif¯am Dental Dif¯am-C ± Hexo-Imotryl Tantum biotic Algolisina Leucorsan

Case report A previously healthy 6-year-old girl, attended the Emergency Room of our Hospital because of the appearance of visual delirium. One day before, she consulted to her primary care doctor because of pruritus vulvae. A vaginal douche preparation of 500 mg benzydamine was prescribed (Benzydamine formulation: powder to be dissolved in 500 mL of water). Fourteen hours before admission and accidentally, her father gave her the topical preparation orally, in 100 mL solution. She vomited immediately, she slept for 2 h and woke up screaming, seeing and feeling ¯ies, worms and birds travelling through her body, biting her and laying eggs. On arrival at our Hospital, the hallucinosis was progressively decreasing, and the

Netherlands South Africa Spain

Switzerland *Correspondence: S Nogue Received 20 January 1999; revised 15 March 1999; accepted 22 March 1999

United Kingdom

Bucco-Tantum Rhino-Tantum Tantum Dif¯am

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± ± Bristaciclina Dental Dolosarto Mentamida Prosturol Tantum Ciclina Viciseptil Otico ± ±

Benzydamine overdose GoÂmez-LoÂpez L et al

472

level, normal re¯exes, symmetrical and reactive pupils, and no signs of meningism. No treatment was required and the episode resolved spontaneously. The patient was discharged 6 h later and after 6 months she remains asymptomatic.

Discussion Benzydamine (N,N-dimethyl-3-[(1-benzyl-1H-indazol-3-yl)ossi]-1-propanamine) is a NSAID with analgesic, anti-in¯ammatory, antipyrexial and antimicrobial properties.1 Absorption through skin and mucose is usually low (less than 10% of total dose). After oral administration of 50 mg doses of benzydamine hydrochloride in an aqueous solution, benzydamine is rapidly absorbed. Approximately the 64% of the dose is absorbed by 1 h, and complete absorption occurs in 4 ± 6 h. Once the drug passes to the vascular territory, it has a relative low systemic clearance (160 ml min71) but high volume of distribution (110 L). After oral doses it reaches a very high bioavailability (87%) and the plasmatic half-life is 7.8 h.2 With an increased dose, longer serum persistence has been demonstrated.3 It is metabolized by the liver and excreted both in the urine and the faeces.2,3 Acute poisoning with NSAIDs is associated with a variety of features. Delirium, hallucinosis and abnormal behaviour due to diclofenac, ibuprofen, indomethacin4 and sulindac,5 have been reported. In our case only hallucinosis was present. NSAIDs can also induce headache, nystagmus, dyplopia, tinnitus, dizziness, blurred vision, seizures, diskynesia, lethargy, loss of consciousness6,7 and coma.6,8 Seizures are more frequently seen with mefenamic acid, but also occur with piroxicam, fenbufen, naproxen and ketoprofen.6,9 Several of these symptoms can occur with therapeutic doses.

Hypotension and tachycardia are sometimes present.6,8 Vomiting is an important early sign of NSAIDs overdose, and abdominal pain, nausea and intestinal bleeding are also frequent gastrointestinal manifestations.6,8,10,11 Acute renal failure has been described in cases of overdose,6,8,12 but has been rarely reported with therapeutic doses.12,13 A case of topical administration of benzydamine has been reported as a cause of renal impairment.14 Granulocytosis,15 pancytopenia and coagulopathy8,9 may also occur in acute NSAID overdose. There are no data in the literature regarding the management of benzydamine overdose. Therefore, the same guidelines recommended for other NSAIDs, namely supportive measures, should be used. Gastric decontamination up to 60 min after the ingestion should be performed by a gastric lavage with activated charcoal,6,16 and a saline cathartic or sorbitol can also be used after the gastric lavage.16 Urine alkalinization and diuresis have been recommended to enhance the elimination of NSAIDs.6 Haemodialysis is unlikely to enhance elimination, due to their kinetic characteristics, but may be required if oliguric renal failure develops.6 There is no known speci®c antidote. To our knowledge, no cases of accidental or voluntary poisoning due to benzydamine have been reported, probably because of the dif®culty of taking high doses accidentally. The amount of this drug in oral presentations is low. In Spain, 250 mL mouthwash containers are marketed, containing 375 mg benzydamine. Tablets containing 25 or 50 mg benzydamine are also available. Topic preparations in powder formulation have a higher quantity of benzydamine (a Rosalgin1 vaginal douche preparation contains 500 mg of benzydamine). This is why benzydamine accidental poisoning in children would be more likely using topical preparations, as in our case.

References 1 Fanaki NH, el-Nakeeb MA. Antimicrobial activity of benzydamine, a non-steroid anti-in¯amatory agent. J Chemother 1992; 4: 347 ± 352. 2 Baldock GA et al. Pharmacokinetics of benzydamine after intravenous, oral, and topical doses to human subjects. Biopharm Drug Dispos 1991; 12: 481 ± 492. 3 Anfossi P et al. Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration. Vet Res Commun 1993; 17: 313 ± 323. 4 Bright TP, McNulty CJ. Suspected central nervous system toxicity from inadvertent nonsteroidal antiin¯ammatory drug overdose. DICP 1991; 25: 1066 ± 1067. 5 Thornton TL. Delirium associated with sulindac. JAMA 1980; 343: 1630 ± 1631.

6 Smolinske SC et al. Toxic effects of nonsteroidal anti-in¯ammatory drugs in overdose. An overview of recent evidence on clinical effects and doseresponse relationships. Drug Saf 1990; 5: 252 ± 274. 7 Lo GC, Chan JY. Piroxicam poisoning. Br Med J 1983; 287: 798. 8 Kolodzik JM, Eilers MA, Angelos MG. Nonesteroidal anti-in¯amatory drugs and coma: a case report af fenoprofen overdose. Ann Emerg Med 1990;19: 378 ± 381. 9 Macdougall LG, Taylor-Smith A, Rothberg AD, Thomson PD. Piroxicam poisoning in a 2-year-old child. A case report. S Afr Med J 1984; 66: 31 ± 33. 10 Mosvold J et al. Overdosage of piroxicam. Acta Med Scand 1984; 216: 335 ± 336.

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11 Davies NM, Jamali F. Pharmacological protection of NSAID-induced intestinal permeability in the rat: effect of tempo and metronidazole as potential free radical scavengers. Hum Exp Toxicol 1997; 16: 345 ± 349. 12 Kulling EJ, Beckman EA, Skagius AS. Renal impairment after acute diclofenac, naproxen, and sulindac overdoses. J Toxicol Clin Toxicol 1995; 35: 711 ± 719. 13 Lindsley CB, Warady BA. Nonsteroidal antiin¯ammatory drugs. Renal toxicity. Review of pediatric issues. Clin Pediatr (Phila) 1990; 29: 10 ± 13.

14 O'Callaghan CA, Andrews PA, Ogg CS. Renal disease and use of topical non-steroidal antiin¯ammatory drugs. Brit Med J 1994; 308: 110 ± 111. 15 Gross GE. Granulocytosis and a sulindac overdose. Ann Intern Med 1982; 96: 793 ± 794. 16 American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. Position statement: gastric lavage. Clinical Toxicology 1997; 35: 711 ± 719.

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