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PubMed1995

Safety and tolerance profile of venlafaxine.

Venlafaxine has been shown in clinical trials to be safe and well tolerated in patients with major depression. Data were pooled from 19 studies in which 2181 patients were given venlafaxine, 451 were given placebo and 591 were given a reference antidepressant (imipramine, trazodone, clomipramine, maprotiline, dothiepin or amineptine). Long-term safety was evaluated in 422 patients who were given venlafaxine for at least 1 year; as well, a total of 229 elderly patients have been treated with venlafaxine, including 66 who were given it for at least 1 year. The adverse events that occurred during short-term treatment in > or = 10% of patients were nausea, headache, insomnia, somnolence, dry mouth, dizziness, constipation, asthenia, sweating and nervousness. In comparator-controlled trials, the frequency of anticholinergic events with the reference agents was approximately twice that with venlafaxine. The safety profile and patient acceptability of venlafaxine are comparable to those of third-generation antidepressants, and possibly better than those of first-generation agents.

Antidepressive Agents, Second-Generation↗
PubMed1997

Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators.

OBJECTIVE: The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. DESIGN: After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 +/- 7 years, blood pressure 168.9 +/- 10.5/ 102.2 +/- 5.0 mmHg (means +/- SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. RESULTS: After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). CONCLUSION: Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

Adult↗
PubMedDate not supplied

First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine.

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.

Adult↗
PubMed1987

Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension.

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1989

An open multicenter study to assess the long-term efficacy, tolerance, and safety of the oral angiotensin converting enzyme inhibitor ramipril in patients with mild to moderate essential hypertension.

Three hundred thirty-one patients with mild to moderate essential hypertension, 182 males and 149 females with a mean age of 54 (range, 17-87 years), were studied for 1 year in a clinical trial with ramipril, an angiotensin converting enzyme (ACE) inhibitor. The patients included had completed double-blind trials with ramipril vs. captopril, HCT, atenolol and ramipril plus piretanide. All cases were treated first with 5 mg ramipril and, where appropriate, also with 25 mg HCT. Adjustment of the dose in the range 1.25-20 mg ramipril was left to the investigator. Overall, a consistent reduction in blood pressure was achieved. Only small changes in mean blood pressure were noted during the 12 months (mean diastolic blood pressure 84.3-86.9 mm Hg, mean systolic blood pressure 145.6-148.2 mm Hg). Two hundred sixty-two (82%) of the 331 patients had diastolic values consistently equal to or lower than 95 mm Hg. There was a downward shift in the dosages upon which the investigators finally settled during the 12-month period in the patients receiving ramipril monotherapy. In patients also receiving HCT the initial dose was increased in most cases. Adverse events were observed in 6.7% of patients taking ramipril alone. The most frequent symptoms were dizziness, asthenia, pain in the upper abdomen and headache. Adverse effects occurred more frequently under continuous additional treatment with HCT, the same symptoms being reported. The clinical trial was prematurely terminated in six patients, in only two cases for medical reasons. The analysis of the laboratory findings revealed no general deterioration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Lercanidipine in type II diabetic patients with mild to moderate arterial hypertension.

This study evaluates the effects of lercanidipine antihypertensive treatment on glucose homeostasis in patients with type II diabetes mellitus with mild to moderate hypertension. Forty patients were enrolled. After a 2-week wash-out period, they were randomly allocated to receive in double-blind manner either 10 mg or 20 mg in single daily administration for 8 weeks. Nonresponding patients after the initial 4 weeks, were titrated up to 20 mg and 30 mg lercanidipine, respectively. At the end of the double-blind treatment, all patients entered in single-blind 4 weeks placebo follow-up. Systolic and diastolic blood pressure significantly decreased in both groups of patients after 4 weeks of treatment, and decreased further during the following 4 weeks. In both groups, progressive and significant decrease in fasting blood glucose, glycosylated hemoglobin and area under the curve of the oral glucose tolerance test were detected during lercanidipine treatment. Similarly, a decrease in serum fructosamine values were also observed. All variables returned to towards baseline values during the placebo follow-up period. Adverse events (headache and mild asthenia) were limited to two patients and resolved spontaneously. These data indicate that lercanidipine is effective in lowering high blood pressure in hypertensive patients with type II diabetes mellitus and does not exert negative effects on glucose homeostasis.

Adolescent↗
PubMed2000

Fat augmentation for glottic insufficiency.

OBJECTIVES: Fat lipoinjection augmentation for glottic insufficiency has been used in patients with vocal fold paralysis. Relatively little information is available on the effectiveness of fat injection in patients with vocal atrophy, intubation trauma, and post-hemilaryngectomy defects. STUDY DESIGN: This paper retrospectively compares the efficiency of fat injection in patients with vocal cord paralysis (n = 9), vocal scar (n = 13), and vocal atrophy (n = 11). METHODS: The perceptual acoustic, phonatory function, and videolaryngostroboscopic data were evaluated before and after fat augmentation in 33 patients. RESULTS: Mean follow-up time was 9.7 months. Nineteen patients had excellent results. Three patients had no change. Five patients had late failure. Six patients were lost to follow-up. Phonatory function showed significant improvement in jitter, shimmer, noise-to-harmonic ratio, maximal phonation time, grade, asthenia, and breathiness (P < .05). Videolaryngostroboscopic rating showed significant improvement in right linearity of the vocal fold edge, amplitude of vocal fold vibration, excursion of the mucosal wave, vibratory behavior, and phase symmetry (P < .05). Anterior defects did better than posterior defects. Small vocal fold defects did better than large defects. CONCLUSIONS: Fat injection is a good autogenous implant and may be considered as an option in management of patients with vocal fold scar, defect, or atrophy. Reabsorption of fat is a problem, but the procedure may be repeated.

Adipose Tissue↗
PubMed2002

Functional analysis after supracricoid partial laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVES: To assess prospectively speech and swallowing function in a series of 17 patients after supracricoid partial laryngectomy with cricohyoidoepiglottopexy. STUDY DESIGN: Retrospective study. METHODS: From 1983 to 1996, 69 patients at Department of Otolaryngology-Head and Neck Surgery, CHUV (Lausanne, Switzerland) underwent a supracricoid partial laryngectomy with cricohyoidoepiglottopexy. Seventeen of them (25%) could be contacted and accepted participation in a functional evaluation that included a questionnaire to document their present nutritional status and diet. A formal voice evaluation was also performed, which included psychoacoustic evaluation of vocal qualities, fundamental frequency parameters, phonation intensity range, phonatory quotient (vital capacity divided by maximum phonation time), and a laryngeal video laryngoscopy performed with a rigid endoscope. RESULTS: Median postoperative follow-up was 66 months (range, 12-152 mo). Nine of 17 patients (53%) recovered a normal diet with no increased incidence of aspirations. Seven of 17 had minor limitations such as no peanuts, dry bread, or rice. Two of 17 patients were restricted to pureed food. Assessment of voice showed a clearly decreased mean fundamental frequency at 70.1 Hz (normal range, 121-211 Hz) and a narrowed frequency range of phonation with a mean value of 8.8 semitones (normal value, 27). Forty-two percent of the patients went back to their normal professional life after the operation. Among the 10 who did not, 3 (16%) retired and 7 actually had to give up their profession, because of the modification of their voice or general asthenia and age close to retirement. CONCLUSION: Restoration of laryngeal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy is satisfactory. Although most of the patients seem to recover normal swallowing function, severe voice alterations appear to be inevitable.

Adult↗
PubMed2003

Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients.

To describe the clinical and immunologic characteristics of patients with adrenal involvement and antiphospholipid syndrome (APS), we conducted a computer-assisted (PubMed) search of the literature to identify all cases of primary adrenal insufficiency associated with antiphospholipid antibodies published in English, French, and Spanish from 1983 (when APS was first defined) through March 2002. We reviewed 86 patients (80 from the literature plus 6 from our cohort); 55% were male, and the mean age at presentation was 43 +/- 16 years. Sixty-one (71%) patients had primary APS, and 14 (16%) had systemic lupus erythematosus. In 31 (36%) patients, adrenal insufficiency was the first clinical manifestation of APS. Abdominal pain was present in 55% of patients, followed by hypotension (54%), fever (40%), nausea or vomiting (31%), weakness or fatigue (31%), and lethargy or altered mental status (19%). The main finding in imaging techniques was compatible with adrenal hemorrhage (59%) and in histopathologic study was a hemorrhagic infarction with vessel thrombosis (55%). Lupus anticoagulant was detected in 97% of patients and the anticardiolipin antibodies titer was positive in 93% of patients. Most patients (95%) were positive for the IgG isotype of anticardiolipin antibodies, whereas 40% were positive for the IgM isotype. Baseline cortisol levels were decreased in 98% of patients, ACTH hormone levels were increased in 96% of patients, and the cosyntropin stimulation test was positive in 100% of patients tested. Steroid replacement therapy was the most frequent treatment (84%), followed by anticoagulation (52%) and aspirin (6%). Thirty-two of 35 (91%) patients with prolonged anticoagulant therapy were in good health with a mean follow-up of 25 months, whereas 25 of the 69 (36%) patients with outcome data available had died. The results of the present review stress the clinical importance of systematic screening for lupus anticoagulant and anticardiolipin antibodies in all cases of adrenal hemorrhage or infarction. An initial screening for hypoadrenalism is mandatory in any antiphospholipid antibody-positive patient who complains of abdominal pain and undue weakness or asthenia.

Abdominal Pain↗
PubMed1997

Intrathecal ciliary neurotrophic factor delivery for treatment of amyotrophic lateral sclerosis (phase I trial).

OBJECTIVE: This Phase I trial of ciliary neurotrophic factor (CNTF) delivered intrathecally for the treatment of patients with amyotrophic lateral sclerosis was designed to determine the safety of this new mode of administration as well as the pharmacokinetics and drug distribution. METHODS: CNTF was administered using a drug pump implanted into the lumbar subarachnoid space in each of four patients with amyotrophic lateral sclerosis. Escalating doses (0.4, 0.8, 1.6, 4, and 8 micrograms/h) were infused for 48 hours per week in 2-week cycles until the highest tolerated dose was achieved. Patients were observed for side effects, and standardized muscle and respiratory function tests were performed. Cerebrospinal fluid (CSF) levels of CNTF were determined using simultaneous lumbar and cervical taps. Plasma and CSF levels of antibodies, CSF cells and protein, and routine blood chemistries were monitored, as were weight and vital signs. RESULTS: Pharmacokinetic studies of four patients demonstrated that the distribution and clearance of recombinant human (rH)CNTF are similar to those of many small, water-soluble agents (morphine, baclofen, clonidine) and that the steady-state concentration of rHCNTF at the cervical level was 18 to 36% of that at the lumbar level. Lumbar CSF levels were in the range of 44 to 1230 ng/ml. Intrathecally administered rHCNTF had different adverse effects than the systemically delivered drug. With intrathecal administration, no asthenia, fever, chills, nausea, weight loss, increased cough, or sputum production was found. All patients who received rHCNTF intrathecally experienced dose-related CSF pleocytosis (primarily lymphocytic) and rises in protein levels. No clinical signs of meningeal irritation, such as stiff neck, photophobias, or nausea, were seen. However, one patient who had lumbar spinal stenosis developed severe burning and cramping leg pain. A second patient developed a severe headache and leg and back cramping. No abnormal clinical chemistry or hematological findings were encountered. Plasma levels of rHCNTF were below detection. Antibodies to rHCNTF were found in the systemic circulation of only one patient. The gradual decline in motor strength and performance of standard skills did not improve or worsen. CONCLUSIONS: In this first trial of a recombinant neurotrophic factor to be administered intrathecally by drug pump, the CNTF was well distributed along the spinal canal. Pain syndromes (headache, radicular pain) that were dose-related occurred in two patients, but systemic side effects, which had been observed with subcutaneous rHCNTF, did not occur. Intrathecal drug pump delivery of neurotrophic factors may be the most appropriate way in which to test the efficacy of these high-molecular weight proteins, because high CSF levels can be achieved without significant systemic side effects.

Activities of Daily Living↗
PubMed1984

Blepharochalasis after a bee sting.

Blepharochalasis is a distinct entity of redundant eyelids. It is characterized by a history of recurrent edema that leads to permanent changes in the eyelids. Even in the young, blepharoplasty may be indicated for psychological reasons or to relieve obstruction of vision, eyelid asthenia, and fatigue. Following surgery, recurrent edema may compromise the results or cause further eyelid changes. Effort should be made to define the etiology of the edema and correct the defect if possible.

Adolescent↗
PubMed2003

Docetaxel and radiotherapy and pancreatic cancer.

PURPOSE: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of weekly docetaxel delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Thirteen patients with histologically proven locally non-resectable advanced adenocarcinoma of the pancreas were enrolled in this study. Patients received 4 weekly doses of docetaxel by 1-hour intravenous (IV) infusion with 40 Gy of external beam radiation therapy during 4 weeks. Patients who were stabilized or in response, received 2 additional cycles of docetaxel with a 10 Gy boost of radiotherapy. Doses were escalated at 10 mg/m2 increments in successive cohorts of 3 new patients until MTD was observed. RESULTS: Four patients received docetaxel at 20 mg/m2/week, 3 at 25 mg/m2/week, 3 at 30 mg/m2/week, and 3 at 35 mg/m2/week. All patients, except 2, were given the treatment in its integrity. The most common toxicities were nausea, vomiting, asthenia, and abdominal pains. Except for 1 patient, all toxicity was reversible and did not exceed grade 3. Hematologic toxicity was mild and has not required treatment interruption. 28% of the patients had to be rehospitalized. A total of 73 cycles was administered with a mean of 4 cycles per patient (2-6). CONCLUSION: Even the MTD was not reached, dose escalation was stopped at 35 mg/m2/week. This dose is comparable to the ones previously published using docetaxel in combination with radiotherapy in other tumors. Three patients achieved stable disease and 1 patient an objective response. This combination of weekly docetaxel and radiotherapy shows a feasible and well-tolerated regimen, with, nonetheless, a significant rate of rehospitalization, for patients with locally advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1997

Side effects of terazosin in the treatment of symptomatic benign prostatic hyperplasia.

In this report, we assess the safety of terazosin in the treatment of patients with symptomatic benign prostatic hyperplasia. We analyzed seven prospectively designed placebo-controlled trials involving 3,080 patients, 1,689 of whom received the study drug in doses ranging from 1 mg to 20 mg daily for a total of 1,282 patient-years of exposure. The most common side effects seen in treated patients were dizziness (10.7%), asthenia (7.5%), and peripheral edema (4.0%). These side effects were generally reported as mild and improved after cessation of therapy. The incidence of withdrawal from the study due to side effects was 14.5% in the treatment arm versus 11.4% in the placebo control arm. Also noted was a statistically significant decreased risk of urinary tract infection and myocardial infarction in the terazosin-treated group. This updated report confirms that terazosin can be administered safely to a population of men with symptomatic benign prostatic hyperplasia with minimal clinically significant side effects.

Adrenergic alpha-Antagonists↗
PubMed2000

Pharmacokinetics and safety of single oral doses of sirolimus (rapamycin) in healthy male volunteers.

A phase I study was conducted to determine the pharmacokinetics, safety, and tolerability of sirolimus, a new immunosuppressive drug, in 45 healthy men between 19 and 36 years of age. Nine subjects in each group were randomly assigned to receive single oral doses of either sirolimus (n = 6) or placebo (n = 3) in group I (0.3 mg/m2), group II (1 mg/m2), group III (3 mg/m2), group IV (5 mg/m2) and group V (8 mg/m2). No serious adverse events occurred during the study. Twenty-eight of the 45 volunteers (62%) reported an adverse event; 19 of 30 (63%) were in the sirolimus group and 9 of 15 (60%) were in the placebo group (ns). Asthenia was the most common adverse event, occurring in 7 of 30 (23%) in the sirolimus group compared with 6 of 15 (40%) in the placebo group (ns). Absorption occurred within 1 hour in all volunteers. Whole blood peak concentration and area under the concentration-time curve increased proportionally with dose. Mean (+/- SD) whole blood terminal disposition half-life (t1/2), apparent oral dose clearance (Cl/F), and volume of distribution (Vss/F) were 82 +/- 12 hours, 278 +/- 117 mL/h x kg and 23 +/- 10 L/kg, respectively. Distribution of sirolimus into formed blood elements was extensive, with a mean whole blood-to-plasma ratio of 36. Single oral doses of sirolimus (0.3 to 8 mg/m2) solution were well tolerated in healthy male volunteers.

Administration, Oral↗
PubMed2004

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature.

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.

Gallbladder Neoplasms↗
PubMed2000

Liver injury due to tetrabamate (Atrium): an analysis of 11 cases.

BACKGROUND: Tetrabamate (Atriums), widely used in the treatment of tremor and ethanol-withdrawal symptoms, has been incriminated as a potential cause of reversible acute hepatitis. OBJECTIVE: We report here on 11 patients who experienced tetrabamate-related liver injury, in order to evaluate their clinical, histopathological and evolutive features. PATIENTS AND METHODS: Between 1987 and 1998, 34 cases of tetrabamate-associated acute hepatitis were spontaneously reported to the regional pharmacovigilance center of Lyon. Eleven cases were considered probably to be drug-induced. RESULTS: There were three males and eight females aged 31-82 years (mean, 57 years). The duration of treatment ranged from 33 to 206 days, and indication for treatment was depressive disorders, tremor or prevention of alcohol withdrawal symptoms. Clinical symptoms were asthenia (n = 9), jaundice (n = 3) and/or diffuse rash (n = 3). The pattern of liver injury was cytolytic (n = 10) or cholestatic (n = 1). Three patients presented biological features of hepatic failure. A percutaneous liver biopsy was performed in six patients. Histological examination of the liver specimen showed a large spectrum of lesions: massive hepatocellular necrosis (n = 1), centrilobular and nonconfluent hepatocyte necrosis (n = 2), intracellular cholestasis (n = 3), and granulomatous hepatitis (n = 1). Tetrabamate was discontinued in all patients. In seven patients, a complete recovery was observed 3 weeks to 3 months after drug withdrawal. Two patients, despite a rapid improvement of liver function tests, died from unrelated causes. The remaining two patients died from irreversible hepatic failure. CONCLUSIONS: Our data strongly suggest that tetrabamate may induce acute liver injury, which may eventually result in life-threatening liver failure.

Adult↗
PubMed2001

Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report.

We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Treatment of Obese Patients with Dexfenfluramine: A Multicenter, Placebo-Controlled Study.

This randomized, placebo-controlled, double-blind study was designed to evaluate the safety and efficacy of dexfenfluramine (Dfen). Dfen 15 mg BID, and placebo were administered for 12 weeks to 337 moderately obese patients on calorically restricted diets. Patients were monitored for an additional 4 weeks. Efficacy was evaluated in 321 patients who were an average of 52% in excess of ideal body weight. Dfen-treated patients lost significantly more weight than did those treated with placebo (p less-than-or-equal 0.001). Small nonsignificant fluctuations in body weight were observed during the 4-week posttreatment period in both groups. The most common drug-related side effects were diarrhea, asthenia, dry mouth, and thirst (p less-than-or-equal 0.05 compared with placebo). Dexfenfluramine may become a valuable addition to weight loss and weight management programs.

Journal Article↗