Pamidronate disodium and possible ocular adverse drug reactions.

Ciba-Geigy Central Epidemiology and Drug Safety Center has received 23 reports of suspected ocular adverse drug reactions associated with the use of intravenous pamidronate disodium, an inhibitor of bone resorption that is used primarily in the management of tumor-induced hypercalcemia and Paget's disease of the bone. Anterior uveitis, bilateral in six of seven patients, occurred within 24 to 48 hours after the drug was administered. The anterior uveitis recurred in four of the five patients who were rechallenged. Three reports involved unilateral episcleritis or scleritis occurring within one to six days after the administration of the drug. Only the episcleritis patient was rechallenged five months later, when the patient again had the episcleritis occur in the same eye. Thirteen patients reported nonspecific transitory conjunctivitis within six to 48 hours after pamidronate disodium was given intravenously. This was positive on rechallenge in six of eight patients. These data indicate that, on rare occasions, pamidronate disodium is a probable cause of anterior uveitis or nonspecific transitory conjunctivitis and is a possible cause of episcleritis or scleritis.

An overview of international clinical trials with halometasone cream.

In international multicentre comparative clinical trials carried out by dermatologists in 717 patients with non-infected acute eczematous dermatoses at 28 trial centres in Austria, Germany, Holland, Switzerland and Yugoslavia, halometasone cream exhibited a very satisfactory therapeutic effect in acute contact dermatitis, atopic dermatitis, nummular dermatitis and seborrhoeic dermatitis. It yielded 'good' to 'very good' results in 89.7% of the 333 patients treated with halometasone cream. Halometasone cream was significantly more effective than Diproderm, Diprosone and Ultralan creams with respect to the overall success rate, the percentage of patients with 'very good' results and early cures. It proved marginally superior to Halciderm cream in therapeutic efficacy. The onset of therapeutic effect was more rapid in patients treated with halometasone cream than in those on treatment with comparative preparations. Halometasone cream was well tolerated and neither skin atrophy nor any systemic effect due to the transcutaneous systemic absorption of the corticoid was observed. In view of the rapid onset of action, very good efficacy and tolerability, halometasone cream, with agreeable cosmetic and applicatory properties, may be considered as a suitable corticosteroid topical for the treatment of acute eczematous and other corticosteroid-responsive dermatoses.

An overview of international clinical trials with halometasone ointment in chronic eczematous dermatoses.

Four international, multicentre, comparative clinical trials were carried out by twenty-two dermatologists in 569 patients with non-infected chronic eczematous dermatoses in Austria, Germany, Spain, Switzerland and Yugoslavia. In these clinical trials halometasone ointment exhibited a very satisfactory therapeutic effect in all the five types of non-infected chronic eczematous dermatitis, namely chronic contact dermatitis, atopic dermatitis, lichen simplex chronicus, seborrhoeic dermatitis and nummular dermatitis. It yielded an overall success rate ('good' to 'very good' results) of 85% as against 71% obtained with the comparative preparations. With regard to therapeutic effect, halometasone ointment proved significantly superior (p = 0.0001) to Ultralan ointment but it was less effective than Dermovate ointment (p = 0.052). It yielded overall success rates higher than those obtained with Diproderm (84.6% versus 74.4%) and Synalar (88.5% versus 72%) ointments. Halometasone ointment was well tolerated and neither skin atrophy nor any systemic effect due to the transcutaneous systemic absorption of the corticoid was observed.

A comparative multicentre trial of halometasone/triclosan cream and betamethasone dipropionate/gentamicin sulphate cream in the treatment of infected acute eczematous dermatitis.

A multicentre, between-patient, comparative trial was carried out to compare the efficacy and tolerability of a cream containing 0.05 halometasone and 1% triclosan with those of a cream with 0.05% betametasone dipropionate and 0.1% gentamicin sulphate in patients suffering from infected acute ezcematous dermatoses. In the evaluable trial population, consisting of 265 patients, halometasone/triclosan cream yielded a significantly (p = 0.001) higher success rate ('good' to 'very good' results), namely 96%, than the comparative cream (80%). Halometasone/triclosan cream also displayed a significantly (p = 0.008) higher cure rate (73.9%) than that observed with the comparative preparation (58.6%). The proportion of patients obtaining an early cure, i.e. in less than 20 days, was significantly (p = 0.0005) higher with halometasone/triclosan cream (42.5%) than with the comparative preparation (22.6%). The two preparations did not differ significantly with regard to the incidence and severity of adverse effects.

A comparative multicentre trial of halometasone/triclosan cream and diflucortolone valerate/chlorquinaldol cream in the treatment of acute dermatomycoses.

In this multicentre, between-patient trial the efficacy and tolerability of a cream, containing 0.05% halometasone and 1% triclosan, was compared with those of Nerisona C cream, containing 0.1% diflucortolone valerate and 1% chlorquinaldol, in 183 patients with acute dermatomycoses. Halometasone/triclosan cream and the comparative cream showed closely similar results with respect to good to very good therapeutic effects (60% versus 57%). However, halometasone/triclosan cream proved superior to the comparative preparation with regard to very good (cured) results (53% versus 46%), an early cure in less than 30 days (41% versus 34%) and onset of action within 3 days of starting the treatment (32% versus 18%). Mycological findings were positive on direct microscopy in 36% and 43% and in culture in 19% and 17% of the patients following treatment with halometasone/triclosan cream and the comparative cream preparation, respectively. Adverse effects were reported in seven out of 108 patients treated with halometasone/triclosan cream and in five out of 107 patients treated with the comparative preparation.

Hydrocortisone choleresis in the dog.

Hydrocortisone sodium succinate (Solu-Cortef; Upjohn Co., Kalamazoo, Mich.) has been found to induce choleresis in unanesthetized fasting dogs fitted with Thomas duodenal cannulae for direct quantitative collection of bile. In all experiments, bile flow increased (average, 68%) 15-20 min after beginning hydrocortisone by infusion in association with an equivalent increment in the output of sodium, potassium, chloride, and bicarbonate. In five animals, the choleretic response occurred independently of, and apparently additive to, the effect of simultaneously administered sodium taurocholate. The fluid added to the bile resembled an ultrafiltrate of plasma. Erythritol clearance increased in proportion to flow, suggesting an effect at the hepatocellular rather than ductal level and probably independent, therefore, of endogenous secretin release. Hydrocortisone and its metabolites were excreted in amounts too small to induce choleresis osmotically. Simultaneous administration of sulfobromophthalein sodium blocked the choleretic response without preventing hydrocortisone excretion. The data suggest that a previously ill-defined mechanism of canalicular bile formation, not mediated by bile salt excretion, may be operative in choleretic response to a variety of agents.