Safety profile of aztreonam in clinical trials.

The clinical safety of aztreonam in the treatment of suspected aerobic gram-negative infections was assessed in 346 patients who received single doses and in 2,388 patients who received multiple doses. Of those administered multiple doses, 163 (6.8%) experienced 172 adverse clinical effects. The most common were local reactions at the injection site, rash, diarrhea, and nausea and/or vomiting. Among aztreonam and control groups, three-fold increases in serum aspartate aminotransferase (SGOT) and serum alanine aminotransferase (SGPT) values occurred at comparably low frequencies; the mean values of SGOT and SGPT were slightly higher in patients administered aztreonam than in those given cefamandole. Treatment with aztreonam was discontinued in 51 (2.1%) of 2,388 patients because of adverse clinical effects or abnormal laboratory test values. Suprainfections (infections due to new pathogens occurring at the original site of infection during treatment with the study drug that were treated with another antibiotic) were reported in 2%-6% of aztreonam-treated patients, a frequency similar to that observed in control groups. Aztreonam is well tolerated and has a safety profile similar to that of other beta-lactam antibiotics.

Crossover comparison of captopril and propranolol as step 2 agents in hypertension.

The efficacy of captopril treatment was compared with that of propranolol in a single-blind crossover study in 14 patients with essential hypertension uncontrolled on diuretic alone. Both captopril (37.5 to 75 mg daily) and propranolol (60 to 120 mg daily), in combination with hydrochlorothiazide (50 mg daily), caused a significant fall in sitting systolic and diastolic blood pressure. Heart rate, plasma renin activity, and plasma aldosterone data were consistent with the effects of converting enzyme inhibition or beta blockade. Both drugs were well tolerated. Captopril appeared to be equivalent in efficacy and safety to propranolol when added to hydrochlorothiazide. It may be considered as an alternative step 2 antihypertensive agent, especially in patients experiencing unwanted effects on beta blockers.

Captopril in hypertension; seven years later.

Captopril was first administered to hypertensive patients 7 years ago. The relatively high dosage employed and the severity of diseases in the patient population initially led to a high frequency of side effects. Subsequently, an increase in the time intervals for dose titration and the earlier addition of a diuretic have made it possible to reduce the daily dose, thus significantly improving the drug's safety profile without compromising its antihypertensive effect. In a worldwide postmarketing surveillance study of captopril, 6,737 hypertensive patients were enrolled, of whom 3,219 were treated for at least 1 year. Patients had a mean entry blood pressure of 183 (+/- 31)/111 (+/- 16) mm Hg while still receiving an average of 2.3 antihypertensive drugs. However, 10.3% were not receiving therapy before entering the study. 1,811 patients (29% of those for whom relevant data were available) had impaired renal function on entry (serum creatinine concentration greater than or equal to 1.6 mg/dl). The hypertension of 881 of the patients (13.1%) was classified as mild to moderate. By design, the types of patients, dosage schedules, and patient monitoring requirements were consistent with the recommendations of the manufacturer at the time the study was initiated. The results of the study showed that long-term antihypertensive efficacy was maintained with a mean captopril dose of approximately 150 mg/day, when used either as monotherapy or more frequently with a diuretic. This dosage was associated with satisfactory control of blood pressure and a considerable reduction in the 12 months' cumulative frequency of drug discontinuation because of adverse reactions (5.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term antihypertensive therapy with captopril.

Most forms of hypertension require life-long treatment; thus, it is important to determine the continuing effectiveness and safety of any new therapeutic agent. While participating in various investigational studies, 7103 hypertensive patients received captopril, of whom 4397 were treated for 3 months to 4 years. The 4-year patients included 2498 with mild or moderate essential hypertension (diastolic pressure less than 120 mm Hg), 893 with severe essential hypertension, and 517 with renovascular hypertension. Repeated examinations of these long-term therapy patients, the majority of whom also were receiving a diuretic, indicated no drug tolerance to the combination, i.e., there was continuing control of the blood pressure without significant increases in dosage or addition of other drugs. Side-effects occurring during the first few months of captopril administration (rash, taste disturbances, and, rarely, neutropenia) were not a problem during prolonged therapy. A few patients (70/7,103, or 1.0%) developed proteinuria, usually reversible and seldom associated with any deterioration of renal function. The proteinuria occurred most often in patients who had preexisting renal disease and were receiving high doses of the drug. There were no significant changes in key biochemical parameters. A total of 230 patients discontinued treatment for failure to maintain adequate blood pressure reduction, and 397 for side-effects. The estimated 4-year cumulative frequency of drug discontinuance for side-effects was 11.6% (life table method), which compares favorably with other classes of antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term treatment of essential hypertension with Nadolol and Hydrochlorothiazide: a two-year follow-up.

After 3 weeks of placebo administration, thirty-two mildly or moderately hypertensive patients were treated with hydrochlorothiazide (HCZ) for 3 weeks, then with HCZ plus nadolol, a new beta-adrenergic blocker, for 2 years. The dose of HCZ was 50 mg once daily for all except two patients, who received 50 mg twice a day. The dose of nadolol ranged from 40 mg to 240 mg, once daily. The average supine blood pressure decreased from 182/110 mm Hg at the end of the placebo period to 170/104 mm Hg at the end of treatment with HCZ alone. Nadolol was added to the regimen, and the average supine blood pressure decreased further to 132/88 mm Hg at the end of 3 months of combined therapy. It remained essentially unchanged for the duration of the 2-year study, and no increases in the dosage of either drug were needed. Side-effects were mild, and none required a change in dosage. A once-daily dose of nadolol combined with HCZ appears to be safe and effective therapy for the long-term treatment of mild or moderate essential hypertension.

Control of essential hypertension with captopril, an angiotensin converting enzyme inhibitor.

1 Captopril, an orally active angiotensin converting enzyme inhibitor, was compared with hydrochlorothiazide (HCT) in the treatment of mild and moderate essential hypertension. 2 Twenty outpatients received no antihypertensive therapy for 2 weeks, after which they were given placebo for 8 weeks. Since their diastolic blood pressure remained above 100 mm Hg, they were then randomized to receive either captopril (twelve patients) or HCT (eight patients) for a 4-week titration period. If the supine diastolic blood pressure (SDBP) was normalized, (less than or equal to 90 mm Hg) by the end of titration period, the established regimen was continued for an 8-week maintenance period; if not, the alternate drug was added in increasing doses for up to 4 weeks and the combined therapy was maintained for the remaining 4 weeks. 3 After the first 4 weeks of therapy, both groups showed a statistically significant decrease in both systolic and diastolic blood pressure. Normalization of SDBP occurred in 75% of patients treated with captopril alone, and the addition of HCT produced normalization in the remainder. HCT alone resulted in normalization of SDBP in 50% of patients and the blood pressure of the remaining patients was normalized after the addition of captopril. 4 Captopril given orally, either alone or in conjunction with HCT, is an effective agent for the control of mild and moderate essential hypertension. 5 In our series the main side effects encountered were vertigo and dizziness, transient eosinophilia, a rise of BUN and or/a rise of SGPT or SGOT.

Nadolol and propranolol in the treatment of hypertension: a double-blind comparison.

Nadolol and propranolol were compared in seventy-five hypertensive patients in a double-blind randomized study conducted at Ain-Shams Hospital. After an initial wash-out period of 5 weeks, including 3 weeks of placebo administration, forty-five patients were given nadolol once daily and thirty patients received propranolol four times per day for 12 weeks, followed by a tapering-off period of 2 weeks. Both beta-blocking agents were effective in controlling hypertension with final daily doses ranging from 80 to 320 mg. Of statistical significance, however, were the better responses of supine systolic blood pressure elicited by nadolol. The only adverse reactions that occurred in this series were slight weight gains in two patients treated with nadolol and moderate dizziness in one patient treated with propranolol. Nadolol was proved to be a safe antihypertensive drug, at least comparable to propranolol in efficacy, with the advantages of a once-daily dose and a lack of direct depressant action on the heart.

Long-term treatment of essential hypertension using nadolol and hydrochlorothiazide combined.

1 The stepped care approach for the treatment of hypertension was adopted in a study at Ain Shams Hospital using hydrochlorothiazide (HCT) and a new beta-blocker, nadolol. Sixty mild to moderately hypertensive patients were studied for 20 weeks (2 weeks no antihypertendive the therapy, 3 weeks placebo, 3 weeks HCT, 4 weeks nadolol + HCT dose titration and 8 weeks nadolol + HCT maintenance). The dose of HCT was 50 mg once daily throughout the study except for six patients who had their HCT dose increased to 100 mg daily during maintenance. The dose of nadolol ranged from 40-240 mg daily. 2 No patient on HCT monotherapy achieved full control of his supine diastolic blood pressure (SDBP less than 90 mm Hg). On combined therapy, 55 patients (91.7%) showed a full response, whereas the remaining five patients a good or adequate response. 3 Thirty-two of these patients agreed to continue in the study for a further 21 months (totalling 2 yr of therapy). To date, 15 of them have completed a total of 10 months, 7 have completed 11 months and 10 have completed 12 months. The delta percentage decrease in supine BP continued to be 28.0 and 19.5 for systolic and diastolic BPs respectively. 4 No significant changes in funduscopies, chest X-rays, ECGs, or full laboratory investigations were noted. A few side-effects of mild nature occurred. None necessitated discontinuation of therapy. 5 Combined therapy with nadolol and HCT is a safe and effective method of controlling hypertension over extended periods.

Double-blind paired comparison clinical trial of halcinonide and hydrocortisone.

Fifty patients with a diagnosis of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis and with bilateral symmetric lesions of equal severity participated in this study. A double-blind paired comparison technique was used in which halcinonide-neomycin-amphotericin ointment was applied to the lesions on one side of the body and hydrocortisone ointment to similar lesions on the other side according to a randomized schedule. The halcinonide-containing combination was statistically superior (p less than 0.05) to hydrocortisone ointment in the treatment of psoriasis patients. No statistically significant difference between the two drugs was obtained for the three other indications studied. No side effects with either ointment were observed. Halcinonide as formulated in this combination is an effective and safe corticosteroid.

A comparative study of epicillin and chloramphenicol in the treatment of enteric fever.

One hundred patients with acute enteric fever were randomly assigned to treatment with either chloramphenicol 50 mg/kg body-weight or epicillin 1 g six hourly. Eighty-one patients had a positive blood culture for typhoid or paratyphoid bacilli and nineteen had a positive stool culture with a significant Widal titre. All fifty patients in the group treated with chloramphenicol responded, however there was one relapse with bacteraemia. In the group treated with epicillin, six from the total of fifty patients were considred treatment failures. Treatment was considred as a failure if the patient was febrile after ten days treatment or if there was a deterioration despite antibiotic therapy.

Clinical and bacteriological evaluation of a twice daily regimen of epicillin capsules for the treatment of skin infections.

Fifty-five patients with impetigo, ecthyma, or folliculitis caused by epicillin-sensitive strains of Streptococcus pyogenes or Staphylococcus aureus were treated with 500 mg epicillin capsules twice daily for an average duration of 9 days. Bacteriological and clinical examinations were performed at 2-day intervals. Favourable clinical responses (excellent or good) were obtained in 95% of the patients. No side effects were observed.

A double-blind comparison of a new combination (halcinonide-neomycin-amphotericin) and active controls in cutaneous candidiasis and steroid-responsive dermatoses.

One hundred patients participated in the studies of cutaneous candidiasis and steroid-responsive dermatoses. Seventy patients with the former diagnosis were treated with either halcinonide-neomycin-amphotericin or hydrocortisone-iodochlorhydroxyquin ointment combinations on a double-blind parallel comparison basis. Similar results were obtained after both therapies. Thirty patients with symmetrical bilateral lesions of steroid-responsive dermatoses were treated with halcinonide-neomycin-amphotericin cream on the lesions on one side of the body and hydrocortisone-iodochlorhydroxyquin cream on the opposite side. A double-blind design was used in directly comparing the response to each of the two drugs. Considering the results of all dermatoses together the test combination was statistically superior to the control cream (p less than 0-05). However, while numerical superiority of good responses to the halcinonide combination was recorded in psoriasis, no statistical significance could be derived due to the limited number of cases. No side-effects occurred with any drug combination use. In the opinion of the authors halcinonide-neomycin-amphotericin cream and ointment are safe and effective in the treatment of cutaneous candiasis and steroid-responsive dermatoses.

The value of epicillin and ampicillin in the treatment of meningococcal and pneumococcal meningitis.

96 patients with meningitis due to Neisseria meningitidis and Diplococcus pneumoniae were treated with epicillin or ampicillin according to a predesigned randomization chart. Results indicate that epicillin and ampicillin are effective single drugs in the treatment of meningococcal and pneumococcal meningitis. No adverse reactions were noted with either drug and they were comparable in their efficacy.

A comparative clinical evaluation of a new topical steroid 'halcinonide' and hydrocortisone in steroid-responsive dermatoses.

Fifty patients with symmetrical, bilateral lesions of psoriasis, eczematous dermatitis, atopic dermatitis, or neurodermatitis participated in a double-blind paired comparison study in which 0-1% halcinonide (in a cream formulation containing also neomycin and nystatin) was applied to the lesions on one side of the body and 1% hydrocortisone cream to those on the opposite side for two to three weeks. The number of excellent responses to therapy showed the halcinonide combination to be significantly superior (p less than 0-01) to the control cream in all diagnostic categories if considered collectively, and in psoriasis if the responses were grouped according to diagnosis. No adverse reactions occurred during the trial.