Biomedical subjects

P Benfield

Publications and source records attributed to P Benfield.

At least 19 recordsLinked to original sources

PubMed1998

Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders.

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in Drugs in 1991. Since then, more comparative trials with other antidepressants have become available, and its use in the elderly and as long term maintenance therapy has been investigated. Paroxetine has also been studied in several other disorders with a presumed serotonergic component, primarily obsessive compulsive disorder (OCD) and panic disorder. In short term clinical trials in patients with depression, paroxetine produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with other agents including tricyclic antidepressants (TCAs), maprotiline, nefazodone and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline. Long term data suggest that paroxetine is effective in preventing relapse or recurrence of depression in patients treated for up to 1 year. In the elderly, the overall efficacy of paroxetine was at least as good as that of comparator agents. In short term clinical trials involving patients with OCD or panic disorder, paroxetine was significantly more effective than placebo and of similar efficacy to clomipramine. Limited long term data show that paroxetine is effective in maintaining a therapeutic response over periods of 1 year (OCD) and up to 6 months (panic disorder). Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache. Like the other SSRIs, paroxetine is better tolerated than the TCAs, causing few anticholinergic adverse effects. The most commonly reported adverse event associated with paroxetine treatment is nausea, although this is generally mild and subsides with continued use. Fewer withdrawals from treatment due to adverse effects occurred with paroxetine treatment than with TCAs. The adverse events profile of paroxetine appears to be broadly similar to that of other SSRIs, although data from comparative trials are limited. Serious adverse effects associated with paroxetine are very rare. In conclusion, paroxetine is effective and well tolerated, and suitable as first-line therapy for depression. It also appears to be a useful alternative to other available agents for the treatment of patients with OCD or panic disorder.

Antidepressive Agents, Second-Generation↗

PubMed1998

Topical mometasone. A review of its pharmacological properties and therapeutic use in the treatment of dermatological disorders.

Mometasone, a synthetic 16 alpha-methyl analogue of beclomethasone, is classified as a 'potent' glucocorticoid for dermatological use. It is available as 0.1% cream, ointment and lotion formulations for the treatment of patients with inflammatory glucocorticoid-responsive dermatoses. In patients with atopic dermatitis, the effect of mometasone 0.1% applied once daily over 2 to 3 weeks were similar to those of other glucocorticoids of similar potency, such as betamethasone dipropionate 0.05% twice daily and methylprednisolone aceponate 0.1% once daily. Mometasone 0.1% was significantly superior to twice-daily application of less potent glucocorticoids such as clobetasone 0.05%, hydrocortisone 1.0%, hydrocortisone butyrate and hydrocortisone valerate 0.2%. In patients with seborrhoeic dermatitis, mometasone 0.1% was more effective than ketoconazole 2.0% and hydrocortisone 1.0% in trials lasting 4 or 6 weeks. In the management of scalp psoriasis and psoriasis vulgaris, mometasone 0.1% applied once daily for 2 to 8 weeks was generally more effective than other glucocorticoids of similar or weaker potency such as betamethasone valerate 0.1%, fluocinolone acetonide 0.025%, fluticasone propionate 0.005%, triamcinolone acetonide 0.1% and hydrocortisone 1.0% and as effective as diflucortolone valerate 0.1%. Alternate day application of mometasone 0.1% for 2 weeks was as effective as once-daily application in maintaining symptom control in a small number of patients with psoriasis vulgaris. Although mometasone demonstrates greater anti-inflammatory activity and a longer duration of action than betamethasone, it has low potential to cause adverse systemic effects such as suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, its atrophogenic potential is low and no greater than that of other glucocorticoids in its class, such as betamethasone valerate. Transient, mild to moderate, local adverse effects such as burning, stinging, folliculitis, dryness, acneiform eruptions and signs of skin atrophy have been reported with mometasone. Mometasone has shown a low risk of primary sensitisation and cross-reactions in preliminary patch test studies. Mometasone is a well tolerated topical glucocorticoid effective in the management of patients with atopic dermatitis, seborrhoeic dermatitis, scalp psoriasis and psoriasis vulgaris. In addition to its low potential for causing primary sensitisation and cross-reactions with other topical glucocorticoids, mometasone offers the convenience of once-daily administration.

Administration, Topical↗

PubMed1998

Tazarotene.

Tazarotene is a topical retinoid that appears to exert its effects via retinoic acid receptors. It normalises differentiation and proliferation of keratinocytes and has an anti-inflammatory effect. Topical tazarotene 0.05% or 0.1% gel was effective in the treatment of plaque psoriasis in clinical trials and its therapeutic effect was maintained for at least 12 weeks after treatment discontinuation in some patients. In one study in patients with psoriasis, tazarotene had similar efficacy to fluocinonide in reducing plaque elevation, but not erythema. In another study, tazarotene was reported to be less effective than fluocinonide. Combination treatment with tazarotene plus a mid- or high-potency corticosteroid was more effective in the treatment of psoriasis than tazarotene alone. Topical tazarotene 0.1% gel significantly reduced lesion counts in patients with mild to moderate facial acne vulgaris. Skin irritation is a common adverse event with topical tazarotene, but it is mainly of mild to moderate severity. Tazarotene is not recommended for use in women who are, or may become, pregnant.

Clinical Trials as Topic↗

PubMed1998

Orlistat.

Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during < or = 2 years' orlistat treatment; serum triglyceride and high density and very low density lipoprotein-cholesterol levels were unchanged in trials of < or = 12 weeks. Obese patients who were maintained on a hypocaloric diet and who received orlistat 360 mg/day for 12 weeks lost a significantly greater percentage of bodyweight than placebo recipients (5 vs 3.5%). In 2-year studies, weight loss was significantly greater in orlistat than in placebo recipients by the end of year 1; weight was further reduced or maintained in the second year, when a eucaloric diet was allowed, in orlistat but not placebo recipients. A greater proportion of orlistat than placebo recipients lost > 5% or > 10% of their initial bodyweight in 1- and 2-year studies.

Drug Tolerance↗

PubMed1998

Cefotaxime. A pharmacoeconomic review of its use in the treatment of infections.

Cefotaxime is a parenterally administered third generation cephalosporin with a broad spectrum of antimicrobial activity. After more than a decade of use, cefotaxime continues to play an important role in the treatment of patients with serious infections, particularly those caused by Gram-negative bacteria. Clinical trials of cefotaxime have demonstrated clinical and/or bacteriological success rates usually between 75 and 100% in hospitalised patients with infections such as pneumonia, complicated urinary tract infections and bacteraemia. In general, comparative trials have shown that cefotaxime has equivalent clinical efficacy to ceftriaxone. Although cefotaxime was traditionally administered at 6- or 8-hourly intervals, evaluations of twice daily regimens have demonstrated the feasibility of using this extended dosage interval in selected patients. Like other parenterally administered cephalosporins, cefotaxime is well tolerated. Cefotaxime does not cause a significant incidence of coagulopathies, as observed with some cephalosporins (e.g., cefamandole and cefoperazone), nor is it associated with the development of pseudocholelithiasis as seen with ceftriaxone. Some hospitals have achieved significant cost savings by implementing programmes or policies involving replacement of prescriptions for ceftriaxone with those for cefotaxime; however, other institutions have shown cost savings when cefotaxime is replaced by ceftriaxone. Similarly, conflicting results were seen in studies that assessed only the drug acquisition and administration supply costs (with or without inclusion of labour costs), highlighting the difficulty in applying pharmacoeconomic data from one clinical setting to another. A limited number of detailed pharmacoeconomic analyses of cefotaxime have been conducted. One analysis, in patients with pneumonia or other serious infections, incorporated published clinical trial data as well as published or estimated cost data (from 1992 or earlier) for the US healthcare setting. Total treatment costs per patient-day were $US25.21 for cefotaxime 1 g twice daily and $US37.23 for cefotaxime 1 g 3 times daily, compared with $US69.97 for ceftriaxone 2 g once daily and $US74.57 for ceftriaxone 1 g twice daily. Costs included those associated with drug acquisition, administration and preparation, laboratory monitoring and adverse events. A large retrospective analysis was conducted between 1989 and 1993 in a US hospital. Patients treated with cefotaxime twice daily had similar clinical outcomes, including duration of hospital stay (7.21 vs 7.24 days), to those receiving antimicrobials other than cefotaxime. However, when a model was applied to determine attributable differences, a trend was demonstrated towards reduced length of hospitalisation (mean reduction 0.5 days) and total cost of hospitalisation (mean reduction $US623 per patient) with cefotaxime. In a Canadian clinical decision-analysis model of initial empirical monotherapy for an average infectious disease state (costs for serious lower respiratory tract infection, urinary tract infection, sepsis, skin/soft tissue infection and febrile neutropenia were weighted according to the incidence of each infection and combined to give a single value), the average total cost per patient for cefotaxime was $Can4099 (1994 dollars). This was lower than that for ceftriaxone ($Can4257) but higher than that for cefepime ($Can3945), ciprofloxacin ($Can4008) and ceftazidime ($Can4086). Costs included those related to drug acquisition, preparation and administration, bacterial culture and sensitivity testing, hospitalisation and adverse events. An analysis conducted in France demonstrated that cefotaxime 1 g 3 times daily was associated with total treatment costs equal to or lower than those for ceftriaxone 2 g once daily. The study also evaluated total costs of cefotaxime 1 g twice daily and ceftazidime 1 g 3 times daily; treatment costs associated with cefotaxime were less than on

Bacterial Infections↗

PubMed1998

Meropenem. A pharmacoeconomic review of its use in serious infections.

Meropenem is a carbapenem antibiotic which is active against the majority of aerobic and anaerobic bacteria implicated in serious infections. Its therapeutic efficacy in a wide range of serious infections is similar to that of imipenem/cilastatin and standard combination drug regimens. Hence, meropenem is suitable for use as monotherapy. Although the acquisition cost of meropenem is likely to be higher than that of aminoglycoside- and metronidazole-containing combination regimens, the latter incur additional drug administration costs and potentially higher costs for treatment of adverse effects. In addition, aminoglycoside-containing regimens also incur assay and toxicity monitoring costs. Economic analyses are required to compare overall treatment costs with combination therapy and meropenem. Cost analyses indicate that the ability to give meropenem, but not imipenem/cilastatin, by rapid intravenous bolus injection results in lower drug administration costs than with the standard infusion method. More comprehensive pharmacoeconomic data on meropenem are required. However, assuming that meropenem and imipenem/cilastatin have similar acquisition costs, the option of administering meropenem by bolus injection and its lower epileptogenic potential at high dosages (thus permitting its use in meningitis) should be considered potentially important attributes when choosing a carbapenem antibiotic for inclusion in a hospital formulary.

Bacterial Infections↗

PubMed1998

Fluoxetine. A pharmacoeconomic review of its use in depression.

Depressive illness is a common, often unrecognised and untreated condition with substantial associated costs, particularly indirect costs (e.g. lost productivity and absenteeism). The improved tolerability profile of fluoxetine and associated lower discontinuation rates, the relative safety of the drug in overdosage and its similar efficacy compared with tricyclic antidepressants have provided the main rationale for using this agent in depressed patients. Pharmacoeconomic analyses of fluoxetine have mainly sought to determine whether its higher acquisition cost in comparison with tricyclic antidepressants can be offset by reductions in other costs and whether the use of this agent as first-line therapy can be justified. Studies have also attempted to determine whether the selective serotonin reuptake inhibitors (SSRIs) can be distinguished from one another on pharmacoeconomic grounds; overall efficacy and tolerability of these agents appear to be similar, although tolerability data are conflicting. Most analyses have been of a retrospective database or clinical decision analytic model design; two prospective trials (one conducted in a naturalistic setting) have been conducted. These studies have mainly considered direct treatment costs only from the perspective of the healthcare payer. Available evidence suggests that overall total direct healthcare costs for patients who start antidepressant therapy with fluoxetine are similar to, or lower than, those for patients who start therapy with tricyclic agents or other SSRIs. Offsetting of the higher acquisition cost of fluoxetine compared with that of tricyclic agents may be accounted for by lower in- and outpatient costs with fluoxetine, a possible lower risk of absenteeism from work and lower mean total medical costs associated with acute overdosage. Between-treatment differences in drug use patterns may also, in part, explain the observed differences in total healthcare costs between fluoxetine and other antidepressants. In particular, patients beginning therapy with fluoxetine are more likely to receive treatment regimens that meet minimum recommended guidelines for dosage and duration and are less likely to require treatment switching/augmentation than those receiving tricyclic antidepressants or other SSRIs as initial therapy. In addition, fewer fluoxetine than tricyclic antidepressant recipients discontinue therapy early, and fewer fluoxetine recipients require upward dosage titration or concomitant anxiolytic/ hypnotic medications than patients receiving other SSRIs. In conclusion, fluoxetine is a well established antidepressant which possesses tolerability and safety advantages over the tricyclic agents. The available cost analyses show that these benefits can be obtained without additional overall cost to the healthcare provider. Cost advantages observed to date for fluoxetine over other SSRIs require confirmation.

Antidepressive Agents, Tricyclic↗

PubMed1998

Fosphenytoin. Pharmacoeconomic implications of therapy.

Advantages and disadvantages of Fosphenytoin. Advantages. More rapid intravenous administration than phenytoin and no need for an in-line filter. May be administered by intramuscular injection. Lower potential for local tissue and cardiac toxicity than phenytoin. Associated with less pain and phlebitis at the injection site, fewer reductions in infusion rate and fewer changes of administration site because of injection site complications than phenytoin. Benefits in terms of ease of administration and improved tolerability vs phenytoin have pharmacoeconomic implications which may translate into an overall cost advantage. Disadvantages. Approximately 10-fold higher acquisition cost vs phenytoin. Fosphenytoin is a parenterally administered prodrug of phenytoin, used in the treatment of patients with seizures. Advantages of fosphenytoin over phenytoin include more rapid intravenous administration, no need for an intravenous filter, and a lower potential for local tissue and cardiac toxicity. Unlike phenytoin, fosphenytoin may also be administered by intramuscular injection. Pharmacoeconomic data from a small study of patients with acute seizures in a US emergency department showed an overall cost advantage of fosphenytoin over phenytoin, despite a considerably greater acquisition cost of fosphenytoin. The main cost drivers for phenytoin therapy were treatment costs associated with adverse events. In view of the limited pharmacoeconomic data currently available, it is in the interests of individual institutions to conduct their own formal pharmacoeconomic studies applying local cost data and patterns of clinical practise to determine whether fosphenytoin should replace phenytoin on their formularly list.

Anticonvulsants↗

PubMed1997

Donepezil.

Donepezil is a specific and potent acetylcholinesterase inhibitor according to in vitro data. It displays primarily noncompetitive inhibitory activity. In vivo, donepezil inhibited acetylcholinesterase activity in human erythrocytes and increased extracellular acetylcholine levels in the cerebral cortex and hippocampus of the rat. Donepezil demonstrated efficacy in tests of reference memory in animals, but had less consistent activity in tests of working memory. Donepezil 5 or 10 mg/day was associated with significant improvements in cognitive function [assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)] after 14 and 30 weeks and patient global function (Clinician's Interview-based Impression of Change incorporating caregiver input score) after 30 weeks, compared with placebo, in patients with mild to moderate Alzheimer's disease. After 2 years, donepezil 5 or 10 mg/day was associated with an ADAS-cog score approximately 4 points better than would be expected in untreated patients with mild to moderate Alzheimer's disease. The most common adverse events reported in association with donepezil 5 mg/day were gastrointestinal events (nausea/vomiting, diarrhoea, gastric upset and constipation) and dizziness. No hepatotoxicity was reported after 12 weeks' treatment.

Aged↗

PubMed1997

Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control.

Fentanyl is a synthetic opioid with short-acting analgesic activity after intravenous or subcutaneous administration. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery via the transdermal therapeutic system (TTS). These systems are designed to release the drug into the skin at a constant rate ranging from 25 to 100 micrograms/h, multiple systems can be applied to achieve higher delivery rates. Initially, much of the clinical experience with fentanyl TTS was obtained in patients with acute postoperative pain. However, because of the increased risk of respiratory complications, fentanyl TTS is contraindicated in this setting. Fentanyl TTS is recommended for use in chronic cancer pain. Moreover, in 11 countries worldwide including the US, its use is not restricted to chronic cancer pain; the drug is also available for treatment of general chronic pain, including that of nonmalignant origin. At the start of fentanyl TTS treatment, depot accumulation of the drug within skin tissue results in a significant delay (17 to 48 hours) before maximum plasma concentration is achieved. Approximately half of the cancer patients converted to transdermal fentanyl from other opioid agents required increased dosages after initial application of the patch. However, concomitant use of short-acting morphine maintained pain relief during the titration period, and the use of such supplementary medication decreased with the duration of fentanyl TTS treatment. In patients with chronic cancer pain, changes in visual analogue scale (VAS) pain scores ranged from a 10% increase (worse pain) to > 50% decrease (less pain) during transdermal fentanyl therapy compared with previous opioid treatment. In addition, patient preference for fentanyl TTS was indicated by the number of patient requests (up to 95%) for continued use of the drug at the end of the study. Although fentanyl TTS is contraindicated in patients postoperatively, the efficacy of fentanyl via the transdermal route was investigated in this patient group. Supplementary patient controlled analgesia was significantly reduced in patients who received fentanyl TTS 75 micrograms/h compared with placebo, although this was not apparent until > or = 12 hours after application. Data evaluating pain relief, which was assessed by VAS pain scores, were inconclusive. Preliminary data, although from relatively small numbers of patients, indicate that transdermal fentanyl may be useful in the management of chronic non-malignant pain. Indeed, some patients whose pain was previously uncontrolled became completely pain free. The most frequently occurring adverse events during fentanyl TTS therapy (as with other opioid agents) included vomiting, nausea and constipation, although vomiting and nausea were not clearly associated with the drug. The most serious adverse event was hypoventilation, which occurred more frequently in postoperative (4%) than in cancer patients (2%). In surgical patients, fentanyl-associated respiratory events (reduced respiratory rate and apnoea) generally occurred within 24 hours of patch application; however, there were isolated reports of late onset (> or = 36 hours postsurgery) fentanyl-associated respiratory depression. In cancer patients, the incidence of constipation was reduced by up to two-thirds after switching from oral morphine to transdermal fentanyl. Transient skin irritation associated with the plastic patch or the adhesive, rather than the drug, was reported in a maximum 3% of patients. In summary, transdermal fentanyl is a useful alternative to other opioid agents, which are also recommended on the third step of the WHO analgesic ladder, in the management of chronic malignant pain. Preliminary data indicate that it may be useful in the management of chronic nonmalignant pain. The advantages offered by fentanyl TTS over traditional methods of chronic pain control include its ease of administration, less constipation and the 3-

Analgesics, Opioid↗

PubMed1997

Intranasal fluticasone propionate. A reappraisal of its pharmacology and clinical efficacy in the treatment of rhinitis.

The intranasal corticosteroid fluticasone propionate is an effective agent for the treatment of rhinitis, demonstrating potent local anti-inflammatory activity and little, if any, systemic activity. Intranasal fluticasone propionate has shown clinical efficacy similar to that of other intranasal corticosteroids, including beclomethasone (administered at up to a 2-fold higher dosage than fluticasone), budesonide, flunisolide and triamcinolone acetonide, and provides greater relief from nasal symptoms (including nasal blockage) than antihistamine agents and intranasal sodium cromoglycate. Its efficacy in the treatment of seasonal allergic rhinitis and perennial allergic and nonallergic rhinitis has been demonstrated in large well-controlled studies in which the drug maintained adequate control of symptoms when administered in a once daily dose of 200 micrograms. In addition, fluticasone propionate has shown similar efficacy to that of beclomethasone in the treatment of nasal polyps; however, its use in the postoperative setting requires further investigation. Intranasal fluticasone propionate is well tolerated in the majority of patients, the incidence of adverse events being similar to that seen with placebo. Pharmacoeconomic analyses indicate that intranasal fluticasone propionate is significantly more cost-effective than the antihistamines terfenadine and loratadine. Overall quality of life was improved to a similar extent by fluticasone propionate and beclomethasone. In conclusion, recent clinical experience has confirmed that intranasal fluticasone propionate is a convenient, effective and well tolerated alternative to other intranasal corticosteroids and antihistamines for the treatment of rhinitis when administered once daily.

Administration, Intranasal↗

PubMed1997

Nelfinavir.

Nelfinavir is a protease inhibitor which shows good inhibitory activity against HIV-1. The pattern of HIV-1 resistance to nelfinavir is different from that seen with other protease inhibitors. In healthy male volunteers, administration of single 400 and 800mg doses of nelfinavir with food resulted in area under the plasma concentration-time curve values that were 27 to 50% higher than those achieved in fasted volunteers who received the same doses of the drug. Reductions in plasma HIV RNA to below detectable levels (detection limit 500 copies/ml) were achieved in some patients (number not reported) after 28 days' treatment with nelfinavir 500, 600 or 750 mg twice daily, or 500, 750 or 1000 mg 3 times daily. Combination therapy with nelfinavir and stavudine produced greater reductions in plasma HIV RNA levels that stavudine monotherapy in patients who had not previously received stavudine treatment; mean increases in CD4+ cell counts were also greater in the combination treatment group than in monotherapy recipients. Plasma HIV RNA decreased to below detectable levels in 11 of 12 patients with early onset HIV infection who received a triple regimen of nelfinavir, zidovudine and lamivudine for 16 weeks.

Anti-HIV Agents↗

PubMed1996

Galanthamine.

Galanthamine is a selective acetylcholinesterase inhibitor which has shown potential for the treatment of Alzheimer's disease. Galanthamine is selective for acetylcholinesterase versus butyrylcholinesterase; however, the drug produces greater enzyme inhibition in human erythrocytes than in human brain tissue. Galanthamine attenuates drug-and lesion-induced cognitive deficits in animal models of learning and memory. Preliminary results in patients with Alzheimer's disease have reported galanthamine to be associated with a reduction in cognitive deterioration on some neuropsychiatric rating scales. Nausea and vomiting are the most commonly reported adverse effects; liver toxicity has not been reported to date.

Alzheimer Disease↗

PubMed1996

Verapamil: a review of its pharmacological properties and therapeutic use in coronary artery disease.

Verapamil has well proven efficacy in the treatment of patients with hypertension, and early studies indicated its efficacy in the treatment of coronary artery disease. The efficacy of verapamil relative to placebo in patients with stable angina pectoris is confirmed, and the drug is at least as effective as nifedipine, propranolol or metoprolol and of similar efficacy to bepridil and nicardipine when administered as a conventional or sustained release formulation. Verapamil is the first calcium antagonist to be shown in a double-blind study to significantly reduce mortality and reinfarction rate after acute myocardial infarction in patients without heart failure. In these patients, the reduction in mortality achieved with verapamil was similar to that reported with beta-adrenoceptor antagonists, suggesting that verapamil may be a suitable alternative to beta-blockers as secondary prevention in patients intolerant of these drugs. Recurrence of stenosis in patients who successfully undergo percutaneous transluminal coronary angioplasty (PTCA) limits the usefulness of the procedure. Verapamil has recently been shown to significantly reduce the rate of restenosis in patients with stable angina at risk of recurrence, although these initial results require confirmation. Verapamil, therefore, is effective in the treatment of patients with stable angina pectoris, appears to be an alternative to beta-blockers in selected patients as late start secondary prevention after acute myocardial infarction and has a potential role in preventing recurrent stenosis after PTCA, if initial results are confirmed.

Angina Pectoris↗

PubMed1996

Moclobemide. An update of its pharmacological properties and therapeutic use.

Unlike older monoamine oxidase inhibitors, which irreversibly and nonselectively bind monoamine oxidase (MAO), moclobemide is a reversible and selective inhibitor of the MAO-A isozyme. Moclobemide only weakly potentiates the pressor response induced by tyramine or other indirectly acting sympathomimetics; therefore, there is no need to avoid dietary tyramine or over-the-counter decongestants with moclobemide as there is with older MAO inhibitors. Recent clinical trials and meta-analyses have confirmed the efficacy of moclobemide in the treatment of depressive disorders. Moclobemide has been shown to have similar efficacy to tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and nonselective, irreversible MAO inhibitors. Long term follow-up studies of 6 to 12 months' duration have demonstrated that the antidepressant efficacy of moclobemide is maintained. Moclobemide, given alone or in combination with another antidepressant, has shown some efficacy in patients with refractory depression; however, comparative trials are required to confirm these findings. Data are also available to show clinical efficacy of moclobemide in the management of social phobia. Comparative studies have established that moclobemide is better tolerated at therapeutic dosages and has less toxicity in overdose than TCAs and nonselective, irreversible MAO inhibitors. Moclobemide lacks the anticholinergic, sedative and cardiovascular effects associated with many of the older antidepressants. Compared with SSRIs, moclobemide has a similar overall tolerability, although it tends to cause fewer gastrointestinal effects than the SSRIs and has not been reported to interfere with sexual function. In summary, recent data which confirm and extend its comparative therapeutic efficacy and low potential for adverse effects have established moclobemide as an effective treatment in depressive disorders. The drug is also effective in patients with a primary diagnosis of social phobia. Its lack of adverse anticholinergic, cardiovascular, cognitive and psychomotor effects makes moclobemide a particularly useful option in the elderly or patients with cardiac disease.

Age Factors↗

PubMed1996

Riluzole. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis.

Riluzole, a benzothiazole, affects neurons by 3 mechanisms: by inhibiting excitatory amino acid release, inhibiting events following stimulation of excitatory amino acid receptors and stabilising the inactivated state of voltage-dependent sodium channels. It has demonstrated neuroprotective activity in vivo and in vitro. Results from 2 randomised double-blind placebo-controlled trials in patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) have demonstrated that riluzole can extend survival and/or time to tracheostomy. After 18 months, the relative risk of death or tracheostomy with riluzole 100 mg/day was reduced by 21%. Although riluzole slowed the rate of deterioration in muscle strength in the first trial, this was not confirmed in the second, larger trial. Riluzole had no effect on any other functional or secondary variable. Gastrointestinal effects, anorexia, asthenia, circumoral paraesthesia and dizziness were reported more frequently with riluzole than placebo. Elevated alanine aminotransferase levels were observed in 10.6 versus 3.8% of patients treated with riluzole 100 mg/day versus placebo, leading to treatment withdrawal in 3.8 versus 2.1% of patients. In conclusion, riluzole is the first drug that has been shown to have an effect on survival in patients with ALS. Although the effect of riluzole was modest, it has allowed some insight into the pathogenesis of ALS from which future gains may be made.

Administration, Oral↗

PubMed1996

Granisetron. A pharmacoeconomic evaluation of its use in the prophylaxis of chemotherapy-induced nausea and vomiting.

The efficacy of granisetron in preventing acute nausea and vomiting during the 24 hours following chemotherapy in patients with cancer is equivalent to that of other serotonin 5-HT3 receptor antagonists (ondansetron and tropisetron) and similar to or greater than that of conventional antiemetic regimens such as metoclopramide plus dexamethasone. Like other 5-HT3 receptor antagonists, granisetron is generally well tolerated by most patients and its antiemetic efficacy is enhanced when used concomitantly with dexamethasone. To date, pharmacoeconomic evaluations of granisetron have involved intravenous administration of the drug to adult patients with cancer receiving single-dose or fractionated chemotherapy of moderate to high emetogenic potential. In economic analyses conducted in France, a single dose of granisetron 3mg was associated with a mean direct treatment cost per patient (or per well-controlled patient) approximately 50% lower than that for ondansetron 8mg intravenously followed by 8mg orally every 8 hours for 3 days, in patients receiving single-dose chemotherapy. Direct costs per patient were approximately 20 to 30% lower with granisetron (usually 3 mg/day) than ondansetron (usually 24 to 32 mg/day intravenously) in patients receiving chemotherapy fractionated over several days. Sensitivity analysis showed that the results, were robust to variations in the acquisition costs of the antiemetics. Granisetron also remained more cost effective than ondansetron with variations in the antiemetic dosage regimens, except when the granisetron dosage remained unchanged while the ondansetron dosage was reduced to a single 8mg intravenous dose on each day prior to chemotherapy (and no change in efficacy was assumed). Other economic evaluations suggest that granisetron may be more cost effective than a combined antiemetic regimen of high dose metoclopramide plus dexamethasone, and selected use of granisetron or ondansetron in patients receiving emetogenic chemotherapy can be implemented with relatively small incremental increases to the total cancer treatment budget, albeit with a marked increase in antiemetic acquisition costs. In conclusion, granisetron is an effective and well tolerated agent for the prophylaxis of acute chemotherapy-induced nausea and vomiting, and its selective use in this clinical setting can provide cost-effective antiemetic therapy.

Adult↗

PubMed1996

Cefpodoxime proxetil. An appraisal of its use in antibacterial cost-containment programmes, as stepdown and abbreviated therapy in respiratory tract infections.

Cefpodoxime proxetil is an orally administered prodrug which is converted in vivo to the third generation cephalosporin cefpodoxime. Cefpodoxime has a similar spectrum of antibacterial activity to the parenteral cephalosporins ceftriaxone and cefotaxime and a long elimination half-life, which allows once- or twice-daily administration. Cefpodoxime proxetil has proven efficacy in the treatment of community-acquired pneumonia and upper respiratory tract, skin and soft tissue and urinary tract infections. It has been evaluated for use in cost-containment programmes, as stepdown (parenteral-to-oral conversion) therapy in the treatment of community-acquired pneumonia and as abbreviated therapy in upper respiratory tract infections. Substituting oral for parenteral therapy can achieve considerable savings (in acquisition, delivery and labour costs). Moreover, oral administration has advantages for the patient in terms of comfort and mobility, avoids the hazards of parenteral delivery and may allow earlier discharge from hospital, or even allow home treatment from the outset in low-risk patients. As hospitalisation is usually the major cost component in treating serious infections, considerable savings can be made in this way. Pharmacy-driven stepdown programmes in 2 US hospitals have achieved cost savings by targeting patients with community-acquired pneumonia for early conversion from intravenous ceftriaxone therapy to oral cefpodoxime proxetil. Costs were compared with those from a control group of patients who continued to receive intravenous ceftriaxone until physicians deemed that oral therapy (with various agents) was appropriate. In one study, duration of parenteral therapy in the cefpodoxime proxetil group was reduced from 6.18 to 3.82 days and duration of hospitalisation was reduced from 10.06 to 6.23 days (p < 0.02), with corresponding hospitalisation cost reductions of $US7300 per patient. However, clinical trial data relating to the efficacy of cefpodoxime proxetil as stepdown therapy in patients initially requiring parenteral antibacterials are lacking. Abbreviated (4-to 7-day) cephalosporin regimens appear to be as effective as traditional 10-day penicillin regimens in the treatment of upper respiratory tract infections. Short regimens may improve patient compliance and tolerability, thereby reducing the costs of adverse effects and treatment failures. Data from preliminary clinical studies suggest that a 5-day course of cefpodoxime proxetil is as effective as an 8-day course of amoxicillin/clavulanic acid in treating either acute otitis media or sinusitis, and as effective as a 10-day course of amoxicillin/ clavulanic acid and more effective than a 10-day course of phenoxymethyl- penicillin in the treatment of pharyngotonsillitis. Cefpodoxime proxetil tended to be better tolerated and was associated with better compliance than penicillin-based regimens. Indeed, a pharmacoeconomic study showed that a 10-day regimen of cefpodoxime proxetil was associated with lower costs for treating adverse effects and treatment failures than a 10-day regimen of amoxicillin/clavulanic acid in the treatment of acute otitis media in children. A 5-day course of cefpodoxime proxetil had a lower cost per patient treated per month free of recurrence than a 10-day course of phenoxymethylpenicillin (non-generic) or amoxicillin/clavulanic acid in the treatment of recurrent pharyngotonsillitis. Thus, evidence to date suggests that cefpodoxime proxetil has potential for use as stepdown therapy in community-acquired pneumonia and in abbreviated therapy courses in upper respiratory tract infections. These preliminary observations require confirmation in well designed studies.

Ceftizoxime↗