An 80-year-old woman with insulinoma is treated with Proglicem (diazoxide) 100 mg, 2 tablets daily

Fråga: An 80-year-old woman with insulinoma is treated with Proglicem (diazoxide) 100 mg, 2 tablets daily for 10 days. The patient is suffering from constant nausea and decreased appetite. Stemetil (prochlorperazine) 5 mg twice daily has no effect against the nausea. Other drugs, Lanacrist (digoxine) 0.25 mg daily since long and Isoptin (verapamil) 40 mg times three for one week. Serumcreatinine 130 mL/min. How to treat the nausea?

Sammanfattning: Nausea and vomiting are mentioned among the adverse effects seen during treatment with diazoxide digoxin and verapamil. No specific recommendation for treatment of the symptoms are reffered to. However, in patients with a reduced renal function a reduced dosage of diazoxide is recommended. With a concomitant digoxin-verapamil treatment we recommend measurement of plasma digoxin. If the nausea could not be explained by digoxin, we recommend changing to another antiemetic.

Svar: Diazoxide is registered in Sweden under the name Hyperstat for intravenous treatment of hypertensive crisis. Proglicem (diazoxide) for oral treatment has been prescribed on licens for hypoglycemia due to hyperinsulinism or of other causes (1). Over 90 per cent of diazoxide is bound to plasma proteins and since the plasma half-life of diazoxide is prolonged in patient with impaired kidney function (physiologically seen in this case!), a reduced dosage should be considered (2).

In FASS, nausea and vomiting are mentioned among the most common adverse effects (3) during treatment with Hyperstat. Gastrointestinal disturbances such as nausea and vomiting are mentioned to occur during treatment with Proglicem, one of the references mention it as a rare effect (4). No specific recommendation concerning treatment of the nausea and vomiting due to diazoxide could be found in the literature, this was confirmed by the manufacurer (5).

Verapamil is also known to increase the plasma digoxin concentration by interaction (3). Furthermore nausea is a common side effect also with verapamil (3).

Considering the relatively high dose of Lanacrist (digoxin), the age of the patient, and the interaction with verapamil we recommend measuring of the plasma concentration of digoxin. The nausea might be explained by high digoxin level. If this is not the case, changing to another antiemetic could be tried. 1 Drugline nr 05851 (year 1987)

2 PDR 1995
3 FASS 1996
4 Goodman and Gilman, The pharmacological basis of therapeutics. 1996; 9th ed:

5 Personal communication, Anna Lundgren, Schering-Plough