PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, VOL 3: 4 1-42 (1 994)

LETTER TO THE EDITOR

Calcitonin and Epistaxis

Sir,

Intranasal calcitonin is available in several Euro- pean countries - Greece, Italy, Portugal, and Spain,’ where it is widely prescribed for osteoporo- sis.’ In a clinical trial the administration of intrana- sal calcitonin to 22 patients with Paget’s disease was followed by minor and transient local symp- toms in six patients, prompting withdrawal in one case; two patients complained of mild nose bleed- i ~ ~ g . ~ The authors of a double-blind placebo-con- trolled randomized clinical trial including 208 women with established osteoporosis, concluded that there was virtually no difference between the rates of adverse events among patients receiving intranasal calcitonin, compared to those on pla- cebo. The only local adverse events that were reported were nasal secretions, sneezing, nasal dry- ness, nasal crusts and irritation of the nasal mucosa, but not epi~taxis .~

We report seven cases of epistaxis in women receiving calcitonin for postmenopausal osteopor- osis (five by intranasal route and two by parenteral route), which were reported to the Spanish System of Pharmacovigilance (see Table 1). Epistaxis appeared after the administration of therapeutic

doses of calcitonin; bleeding episodes were mild in all cases and none of them required tamponing manoeuvres. The recovery period was less than 24 h in all cases except in two, in which it took one week. Three patients were concomitantly receiving other drugs (see Table 1). One report described the case of a woman who continued on calcitonin and whose epistaxis persisted.

In the WHO International Drug Monitoring Programme database there are four additional reports of epistaxis among patients treated with intranasal calcitonin.

Spontaneous reporting systems cannot provide estimates of the incidence of a particular adverse reaction because the extent of underreporting is unknown. Six of the seven reports included in Table 1 were collected in Catalonia. In this region, since 1983 a total of 39 adverse reactions to calcitonin have been reported, nine of them attributed to intranasal calcitonin. In 1992 we received nine reports, two of them describing calcitonin-asso- ciated epistaxis; in the same year approximately 3600 patients were being treated with calcitonin in Catalonia (half of them by intranasal route).

Epistaxis can be caused by drugs that interfere with platelet function of haemostasis. Oral antico-

Table 1 -Clinical features of six patients under calcitonin who presented with epistaxis

Age (years) Daily dose Induction Recovery Other drugs (IU) and route* period period

59 52

65 65 61 51 59

50 i.m. I day c 2 4 h Levothyroxin 125 i.m. 4 days 6 days Ketoprofen (topical)

100 i.n. <24h -t Droxicam (oral) 100 i.n. 1 day c 2 4 h No 100 i.n. 10 months c24h No

13 days c 2 4 h No

Paracetamol

100 i.n. 1 month 1 week NOS *I.m., intramuscular; i.n., intranasal. ?Positive rechallenge; the patient continued the treatment with both drugs and epistaxis persisted. $This patient presented an extensive necrotizing rhinitis.

0 1994 by John Wiley & Sons, Ltd.

42 LETTER

agulants, dipyridamol and non-steroidal anti- inflammatory agents have been Epi- staxis could be induced by a specific pharmacologi- cal action of calcitonin o r by a local irritant effect related with the administration route. Although any drug can produce mucosal lesions if adminis- tered by intranasal route, it is noteworthy that two of the seven patients had been treated with calcito- nin by parenteral route. Laboratory data on hae- mostatic status in these patients are not available; however, the fact that two patients had been treated by parenteral route suggests a possible effect of cal- citonin on haemostasis; this might be confined to only those patients with some unknown predispos- ing factor.

ACKNOWLEDGEMENTS

We thank the reporting physicians and Drs R Edwards (WHO Collaborating Centre for Interna- tional Drug Monitoring), F. J. Morales-Olivas (Departament de Farmacologia de la Universitat de Valencia), and A. Gilabert (Divisi6 d’Atenci6 Farmaceutica del Servei Catalh de la Salut). This work was supported by Servei Catala de la Salut.

PILAR ALVAREZ, MD ALBERT FIGUERAS, MD DOLORS CAPELLA, MD

* JOAN-RAMON LAPORTE, MD

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*Addressee for correspondence. Servei de Farmacologia Clinica, Unitat de Farmacologia Clinica, Universitat Autdnoma de Barce- lona, CSU Val1 d’Hebron, 08035 - Barcelona, Spain

REFERENCES

Anonymous. Calcitonin and osteoporotic fractures. Scrip 1992; 1752: 24. Magrini, N., Vaccheri, A. and Montanaro, N. The Italian way of osteoporosis. Lancer 1992; 339 499- 500. de Deuxchaines, N. New modes of administration of salmon calcitonin in Paget’s disease. Clinical Ortho- paedics 1987; 217: 56-71. Overgaard, K., Hansem, A. M., Jensen, S. B. and Christiansen, C. Effect of salcatonin given intrana- sally on bone mass and fracture rates in established osteoporosis: a dose-response study. British Medical Journal 1992; 305: 556-561. Watson, M. G . and Shenoi, P. M. Drug-induced epi- staxis? Journal of the Royal Society of Medicine 1990;

Mittelman, M., Lewinski, V., Ogarten, U. and Djal- detti, M. Dipyridamole-induced epistaxis. Annals of Otology, Rhinology and Laryngology 1986; 95: 302- 303. Ahmad, S . Lovastatin-warfarin interaction. Archives of Internal Medicine 1990; 150: 2407.

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0 1994 by John Wiley & Sons, Ltd. PHARMACOEPlDEMlOLOGY AND DRUG SAFETY, VOL. 3: 4142 (1994)