Severe electrolyte disturbances and renal failure in elderly patients with combined diuretic therapy including xipamid.

UNLABELLED: Diuretics are among the most frequently prescribed substances in elderly patients, but they are also associated with the highest incidence of adverse effects in this group of patients. Xipamide is a sulfonamide-like diuretic whose action does not depend on transtubular secretion. This characteristic makes it suitable for situations in which the kidney is highly sodium avid. Because of the potency of this substance the risk of adverse reactions like electrolyte disorders or hypovolemia is increased as well. We report seven patients (age 65-85) admitted to the emergency room of the University Hospital of Innsbruck between 1998 and 2002 who had developed serious adverse reactions upon initiation of treatment with xipamide as an additional diuretic. Six of these patients had received combinations with loop diuretics. The disturbances observed were hyponatremia (lowest value 108 mmol/l), hypokalemia (lowest value 1.5 mmol/l) and prerenal azotemia (highest serum urea 269 mg/dl, highest serum creatinine 5.13). CONCLUSION: With the exception of diuretic resistance in severe heart failure or renal insufficiency a combination therapy of xipamide with a second diuretic appears to be associated with an unnecessarily high risk of serious adverse reactions and thus should be avoided. This is especially true for elderly patients.

[Photosensitivity following enoxacin and xipamide: combined phototoxic and photo-allergic reaction to enoxacin, photo-allergic reaction to xipamide with subsequent transient light reaction]. / Photosensitivität nach Enoxacin und Xipamid: Kombinierte phototoxische und photoallergische Reaktion auf Enoxacin, photoallergische Reaktion auf Xipamid mit nachfolgender transienter Lichtreaktion.

In a 51-year-old female patient, we observed a combined phototoxic and photoallergic reaction to Enoxacin, a photoallergic reaction to Xipamide, as well as increased sensitivity to light after withdrawal of the drugs. This unusual diagnosis was based on the clinical picture, graded radiation with UV-A and UV-B, the irradiated intradermal assay, and histological findings. To the best of our knowledge, this is the first report on a photoallergic reaction to Xipamide associated with a combined phototoxic and photoallergic reaction to Enoxacin.

Comparison of two combined diuretics in the treatment of essential hypertension.

The efficacy and safety of two combination drugs, consisting of a diuretic + a K-sparing agent, were investigated in the treatment of essential hypertension. A double-blind, randomized, parallel group study design was employed. After randomization, 14 patients were treated with 10 mg xipamide + 30 mg triamterene (A) and 16 with 25 mg hydrochlorothiazide + 50 mg triamterene (B). The patients suffered from essential hypertension with a systolic blood pressure (SBP) at entry of greater than or equal to 150 mmHg and a diastolic blood pressure (DBP) of greater than or equal to 95 mmHg. After 6 weeks, mean decline in DBP was 12% in group A and 9% in group B, respectively. With treatment A, one patient became hypokalemic and with treatment B one patient became hyperkalemic.

[Photoallergy to Neotri and cross reaction to tenoretic--detection by systemic photoprovocation]. / Photoallergie auf Neotri mit Kreuzreaktion auf Teneretic--Nachweis durch systemische Photoprovokation.

A patient is presented who suffered for 3 years from increasing photosensitivity with chronic eczematous lesions in sun-exposed areas. He had taken one Neotri (triamterene, xipamide) tablet daily for 6 years. After discontinuation of the drug, phototesting and a photopatch test failed to reveal pathological reactions. Eczematous lesions, however, were induced in test areas upon systemic photochallenging with Neotri. One year later, after the antihypertensive medication had been changed from Adalat (nifedipine) to Teneretic (atenolol, chlortalidone) the eczematous photosensitive reaction recurred. Since both xipamide and chlortalidone have a chlorsulfamoyl-substituted aromatic ring in common, it seems that a photoallergic cross-reaction occurred.

Xipamide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy.

Xipamide is a diuretic derived from salicylic acid and has a structural resemblance to chlorthalidone. Its pharmacodynamic profile shows a diuretic efficacy is similar to that of frusemide (furosemide) at doses up to 40 mg, but the onset and duration of action are comparable to those of hydrochlorothiazide. Xipamide has been studied mostly in the treatment of mild to moderate essential hypertension, with few controlled studies of its use in oedematous states. The efficacy of xipamide 20 to 40 mg once daily in patients with mild to moderate hypertension is comparable to that of bendrofluazide 5 mg, bumetanide 1 mg or hydrochlorothiazide 50 mg when used alone in newly treated or previously treated patients. The addition of xipamide 20 to 40 mg daily to regimens containing beta-blockers, adrenergic neuron-blocking drugs and/or methyldopa has resulted in a further reduction in blood pressure. A few studies in oedematous states suggest that xipamide 40 to 80 mg is comparable in efficacy to equal doses of frusemide, and that the side effects of hypokalaemia, hyperuricaemia and increased blood glucose in diabetics or latent diabetics are similar to those of other diuretics. Thus, xipamide is a suitable alternative to other diuretics in the treatment of mild to moderate hypertension and combines the efficacy of frusemide with a less abrupt action in the treatment of oedema.

Nadolol in combination with indapamide and xipamide in resistant hypertensives.

Twenty-four hypertensive patients have been studied. All had blood pressure recordings greater than 160/95 mmHg on 3 occasions whilst taking a beta blocker and two other antihypertensive agents in therapeutic doses. Compliance was checked by intermittent urine analysis for the relevant beta-blocker. These difficult to control hypertensives were treated with nadolol alone, nadolol plus indapamide and nadolol plus xipamide each for 2 months in random order. The aim was to reduce the blood pressure to below 160/95 mmHg. The supine blood pressure on nadolol alone (167/100 mmHg) was comparable to that on the previous three drug regimens (157/100 mmHg), the other two treatments were more effective (145/90 and 148/93 mmHg respectively). Hypokalaemia (serum potassium below 3.5 mmol/l) occurred in six individuals but occurred more frequently on xipamide than on indapamide.

A randomized double-blind clinical trial of xipamid and hydrochlorothiazide in essential hypertension.

Seventeen patients with mild to moderate essential hypertension and controlled with antihypertensive drugs were treated with xipamid (40 mg) or hydrochlorothiazide (50 mg) in a double-blind cross-over randomized trial design. After a run-in-period of 2 weeks with placebo, all of them received either of the two drugs. Placebo treatment for 2 weeks decreased both supine as well as standing blood pressure, but it was not statistically significant. Xipamid produced a somewhat greater decrease in blood pressure than hydrochlorothiazide, but the difference was not statistically significant. Similar results were obtained in 12 newly diagnosed cases of mild to moderate essential hypertension treated with xipamid (80 mg) or hydrochlorothiazide (100 mg) daily as single drug treatment in a randomized, double-blind parallel design trial. The side effects produced by both drugs were only mild in nature. No significant changes were produced in serum electrolytes, uric acid and fasting blood glucose in this short term study with either of the drugs.

Effect of xipamide in oedema of renal disease with varying degrees of renal insufficiency: a comparative trial with frusemide.

In an open crossover trial, 15 patients with evidence of renal impairment, defined by proteinuria, raised serum creatinine or impaired creatinine clearance, were randomly allocated to treatment with either 40 mg frusemide or 40 mg xipamide daily for 7 days. After a 3-day mid-point wash-out period, patients were changed the alternative drug for a further 7 days. Assessment measures involved a wide range of clinical and biochemical parameters. Whilst both drugs significantly reduced oedema, xipamide was more effective than frusemide, and this was associated with a significantly greater effect on sodium excretion with xipamide. With the exception of standing systolic blood pressure where the reduction was significantly more pronounced with xipamide, no significant changes in resting systolic, resting diastolic or standing diastolic pressure were observed to be associated with change of treatment. Three patients noticed minor side-effects during xipamide therapy. There were no adverse reactions inpatients taking frusemide.

Xipamide ('Diurexan') in essential hypertension: a 24-month study.

Twenty-two patients with essential hypertension received xipamide as monotherapy for a continuous period of 2 years. At an average single daily dose of 23 mg, the patients showed a mean reduction in standing systolic pressure of 17%, and diastolic of 15% at the end of the study period. Serum potassium levels always remained within the normal range (without potassium supplements), and serum uric acid levels were only slightly above normal, even at the end of the 2-year trial period. Blood sugar levels in 8 patients with pre-existing diabetes mellitus were increased by 30% at the end of the first year of xipamide therapy, but remained stable at this level during the remaining 12 months. Adverse effects were mild and did not require the cessation of therapy.

Once daily treatment of mild to moderate hypertension with xipamid: a controlled study.

A double-blind, placebo controlled, crossover trial of 20 and 40 mg of xipamid once daily in the treatment of mild to moderate hypertension is reported and some of the difficulties and pitfalls of multicentre trials of this type are described. 2 Both doses were significantly more effective in reducing the blood pressure than the placebo and neither was superior to the other. Both produced some potassium loss. Xipamid acted for at least 22 h and was effective in up to 83% of the patients. 3 Further trials are suggested to investigate the activity of a lower dose than 20 mg.