Could tamoxifen (Nolvadex) cause hypertension and tachycardia?/nThe question concerns a 56-year-old

Fråga: Could tamoxifen (Nolvadex) cause hypertension and tachycardia?<br><br>The question concerns a 56-year-old woman who has been treated with tamoxifen 20 mg daily for two years for breast cancer. During the last year the patient has had hypertension, with a blood pressure of 180/110, and tachycardia. Tamoxifen is the only medication the patient uses at present. However, she has previously experienced the same kind of symptoms during treatment with other drugs.

Sammanfattning: With the present information the association between tamoxifen and tachycardia is unclear. Increased blood pressure could theoretically be a secondary effect of water retention, but documentation supporting this theory could not be found.

Svar: Tamoxifen is an antiestrogenic drug commonly used to treat breast cancer. A search in Medline and relevant pharmacological literature reveals no data concerning tachycardia or hypertension as a side effect of tamoxifen. However, tamoxifen may cause water retention (1), which in turn would lead to elevated blood pressure. There is a clinical impression that patients treated with tamoxifen sometimes develop hypertension (6). However, this finding has not been adequately investigated.<br><br>A few cases of prolonged QT-interval in humans have been found. This prolongation would theoretically increase the risk of torsade de pointes arrhythmias. In one study including 53 patients with severe epithelial tumours, treated with high dose tamoxifen and vinblastine, the investigators found asymptomatic prolongation of the QT-interval at doses of tamoxifen > 80 mg/m2 twice daily (2). No data was found concerning vinblastine and this side effect. In another study concerning children with refractory malignant gliomas treated with high doses of tamoxifen (> 40 mg/m2 twice daily), the doses had to be reduced in two children because of asymptomatic prolongation of the QT-interval (3). However, no arrhythmias were detected in these studies. In an in vitro study using rabbit myocytes, incubated with tamoxifen, an inhibition of one of the potassium channels in the cell was observed, possibly explaining a tamoxifen-induced QT-prolongation (4).<br><br>The relationship between the patient´s symptoms and tamoxifen treatment is unclear. Withdrawal of tamoxifen for a short period could be of value for evaluation and does not pose any significant risk for the patient (6).<div id="referenser" style="display:none;">1 FASS 1999 (The Swedish catalogue of approved medical products)<br>2 Trump DL, Smith DC, Ellis PG, Rogers MP, Schold SC, Winer EP, Panella TJ, Jordan VC, Fine RL: High-dose oral tamoxifen, a potential multidrug.resistance-reversal agent: phase I trial in combination with vinblastine. J Natl Cancer Inst 1992; 884: 1811-6<br>3 Pollack IF, DaRosso RC, Robertson PL, Jakacki RL, Mirro JR Jr, Blatt J, Nicholson S, Packer RJ, Allen JC, Cisneros A, Jordan VC: A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood. Clin Cancer Res 1997; 3: 1109-15<br>4 Liu XK, Katchman A, Ebert SN, Woosley RL: The antiestrogen tamoxifen blocks the delayed rectifier potassium current, Ikr, in rabbit ventricular myocytes. J Pharmacol Exp Ther 1998; 287: 877-83<br>5 Drugline no 14060 (year 1997)<br>6 Dr Tommy Fornander, överläkare onkologen HS/SÖS (personal comment)</div>