Biomedical subjects

K L Goa

Publications and source records attributed to K L Goa.

At least 55 records · Page 3Linked to original sources

PubMed2000

Galantamine: a review of its use in Alzheimer's disease.

UNLABELLED: Currently, acetylcholinesterase (AChE) inhibitors are the most promising class of drugs for the treatment of Alzheimer's disease (AD). Galantamine is a reversible, competitive, tertiary alkaloid AChE inhibitor. The drug is selective for AChE rather than butyrylcholinesterase. In addition to inhibition of AChE galantamine interacts allosterically with nicotinic acetylcholine receptors to potentiate the action of agonists at these receptors. Recipients of galantamine 16 or 24 mg/day achieved significant improvements in cognitive and global symptoms relative to placebo recipients in large (n = 285 to 978 patients with mild to moderate AD) well-designed trials of 3 to 6 months' duration. Galantamine also improved activities of daily living in these patients and significantly reduced the requirement for caregiver assistance with activities of daily living. Moreover, galantamine recipients achieved significantly better outcomes on behavioural symptoms than placebo recipients. In a long term study (12 months), galantamine 24 mg/day slowed the progression of symptoms of the disease and maintained cognitive function and activities of daily living in patients with mild to moderate AD. Galantamine was generally well tolerated with the majority of adverse events being mild to moderate in intensity and transient. Predictably, adverse events were cholinergic in nature and generally related to the gastrointestinal system. These effects were reduced in patients receiving the recommended dose escalation regimen. Galantamine had no clinically relevant effects on vital signs, haematological or biochemical laboratory parameters and, importantly, there were no reports of hepatotoxicity. The incidence of serious adverse events was similar between galantamine (8 to 32 mg/day) and placebo groups (6 to 16% of patients across all treatment groups). CONCLUSIONS: Galantamine is an effective well tolerated symptomatic treatment for AD which improves cognition, function and activities of daily living in the short term (up to 6 months) in patients with mild to moderate AD. In addition, it delays the development of behavioural disturbances and psychiatric symptoms, and reduces caregiver burden (as measured by caregiver time). In the long term (up to 1 year), galantamine maintains cognition and activities of daily living. Adverse events associated with galantamine are mainly cholinergic, usually mild to moderate in intensity and transient. Galantamine has been evaluated in several large well-designed studies and, given the relative lack of established treatment options, it may be considered as one of the first-line pharmacological treatments in patients with mild to moderate AD.

Acetylcholinesterase↗

PubMed2000

Amprenavir: a review of its clinical potential in patients with HIV infection.

UNLABELLED: The virological/immunological efficacy of amprenavir-containing combination regimens has been evaluated in a small number of clinical trials in patients with HIV infection. Amprenavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) was more effective than 2 NRTIs (in treatment-naive patients) or amprenavir monotherapy (in treatment-naive or -experienced patients) in double-blind trials. In the only direct comparison with another protease inhibitor as part of triple therapy, amprenavir was less effective than indinavir in treatment-experienced (protease inhibitor-naive) patients. Amprenavir was as effective as other protease inhibitors when given with abacavir in a small nonblind trial. Amprenavir is generally well tolerated (most events are mild or moderate). GI disturbance and rash are the principal treatment-limiting effects. Preclinical data suggest that amprenavir may have a low potential for metabolic disturbances (e.g. lipodystrophy, fat redistribution); such effects have been infrequent in patients treated to date, but longer term experience is needed. 150V is the major HIV protease substitution associated with amprenavir resistance; this mutation is not seen in isolates from patients receiving other available protease inhibitors. Amprenavir-resistant isolates evaluated to date showed no significant cross-resistance to most other protease inhibitors, although some cross-resistance to ritonavir was noted. Many isolates from patients previously treated with other protease inhibitors are susceptible to amprenavir. Amprenavir offers the convenience of twice-daily administration with no food-timing or fluid restrictions, but this may be offset by the large number and size of the capsules. However, pharmacokinetic data support the use of co-administration of amprenavir and ritonavir at reduced dosages, thereby allowing a reduction in the number of amprenavir capsules. CONCLUSIONS: Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). The limited number of studies available and the absence of well controlled comparisons with other triple therapies limits the conclusions that can be drawn at present. The clinical value of amprenavir for patients with isolates which are resistant to other protease inhibitors but sensitive to amprenavir, and in treatment-experienced patients in general, requires further investigation. Further evaluation of the amprenavir/ritonavir combination is awaited with interest. Like other members of its class, amprenavir has a particular profile of tolerability, resistance and administration characteristics which should be carefully considered in relation to the needs of individual patients.

Animals↗

PubMed1999

Oxaliplatin: a review of its use in the management of metastatic colorectal cancer.

UNLABELLED: Oxaliplatin is a cytotoxic agent which, like other platinum compounds, acts primarily by causing inter- and intra-strand cross-links in DNA, thereby inhibiting DNA synthesis. Oxaliplatin has a bulky carrier ligand which is thought to enhance cytotoxicity and abolish cross-resistance between oxaliplatin and other platinum compounds. Phase II and III clinical trials have found oxaliplatin combined with fluorouracil/calcium folinate (leucovorin/folinic acid) to be an effective first- and second-line treatment for patients with metastatic colorectal cancer. First-line triple therapy with oxaliplatin and fluorouracil/calcium folinate achieved significantly higher response rates than fluorouracil/calcium folinate alone in 2 phase III studies (objective response rates 59 vs 23% and 50.7 vs 22.3%). In addition, median progression-free survival was longer with triple therapy in both studies (8.9 vs 5.2 and 8.75 vs 6.0 months). However, there was no significant difference in median duration of survival between treatment groups, although this may be a consequence of the subsequent use of oxaliplatin and/or surgery in patients who relapsed during therapy with fluorouracil/calcium folinate alone. About 30 to 45% of patients (whose disease progressed during or after fluorouracil-based therapy) responded to second-line combination therapy with oxaliplatin and fluorouracil/calcium folinate. Median progression-free survival ranged from 7 to 10 months and the median duration of survival from 10 to 17 months. Objective responses were achieved in 20 and 24% of patients in 2 small trials of first-line oxaliplatin monotherapy and in about 10% of patients given the drug as a second-line option. Peripheral sensory neuropathy is the dose-limiting toxicity associated with oxaliplatin. Severe neurotoxicity has been estimated to occur in 10% of patients after 6 treatment cycles and in 50% after 9 cycles of an oxaliplatin dosage of 130 mg/m2 once every 3 weeks. It is cumulative, but reversible on discontinuation of therapy. Nausea, vomiting and diarrhoea are common, but are usually mild to moderate. Myelosuppression is also observed, but is usually mild. CONCLUSION: oxaliplatin is a promising treatment option for patients with metastatic colorectal cancer. It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone. Promising results have been found in studies of the drug as monotherapy, and oxaliplatin may also prove useful in the neoadjuvant setting in patients with unresectable liver metastases; however, data are limited at present.

Animals↗

PubMed1999

Epirubicin: a review of its intravesical use in superficial bladder cancer.

UNLABELLED: The anthracycline epirubicin has been investigated for intravesical use in patients with superficial bladder cancer. In multicentre, randomised trials, prophylaxis with intravesical epirubicin 30 to 80 mg after transurethral resection (TUR) was more effective than no prophylaxis in the prevention of disease recurrence. Intravesical prophylaxis with epirubicin was as effective as that with equivalent dosages of doxorubicin after TUR. Data are conflicting concerning the relative efficacy of intravesical epirubicin and bacillus Calmette-Guerin (BCG) in patients at intermediate risk of recurrence after TUR, but epirubicin was less effective than BCG in those at high risk. The efficacy and tolerability of prophylaxis with epirubicin relative to that with mitomycin is not yet established. The efficacy of epirubicin as prophylaxis after TUR in combination with BCG or interferon-alpha-2b, or as treatment in patients with superficial bladder cancer has been evaluated in small, noncomparative trials, but requires clarification. Adverse events associated with intravesical epirubicin were generally mild and transient. The most common adverse events were localised to the bladder (cystitis, haematuria and urinary tract infection). Systemic adverse events (cardiac, haematological or related to hypersensitivity) were not reported in many trials of intravesical epirubicin, and when reported generally occurred in < or =5% of patients who received the drug. Intravesical epirubicin was generally tolerated as well as intravesical doxorubicin and was associated with a lower incidence of mild chemical cystitis in 1 clinical trial. The incidence of adverse events associated with intravesical epirubicin was markedly lower than that associated with intravesical BCG. CONCLUSIONS: Intravesical epirubicin has shown efficacy in preventing disease recurrence after TUR of superficial bladder cancer. In comparison with equivalent dosages of doxorubicin, the efficacy of epirubicin for this indication is generally similar, and the tolerability profile may be more favourable. Epirubicin is less effective than BCG as intravesical prophylaxis in patients at high risk of recurrence after TUR; the relative efficacy of epirubicin and BCG after TUR in patients at intermediate risk is not yet clear. Intravesical epirubicin is generally tolerated better than BCG. Intravesical epirubicin may be used as prophylaxis after TUR in patients who are at low or intermediate risk of recurrence of superficial bladder cancer.

Antibiotics, Antineoplastic↗

PubMed1999

Lamifiban.

Lamifiban is an intravenously administered, selective, reversible, nonpeptide glycoprotein IIb/IIIa receptor antagonist which inhibits platelet aggregation and thrombus formation by preventing the binding of fibrinogen to platelets. In trials in patients with non-Q wave myocardial infarction (MI) or unstable angina pectoris (PARAGON A and the Canadian Lamifiban Study), the incidence of clinical events at 30 days in patients receiving lamifiban (1 to 5 microg/min) was not significantly different from that in patients receiving aspirin plus heparin or aspirin alone. In PARAGON A, the incidence of clinical events at 6 months was significantly lower after lamifiban (with or without heparin) and aspirin therapy than after standard heparin and aspirin therapy. A large phase III trial (PARAGON B) is under way comparing lamifiban plus aspirin and heparin with standard aspirin and heparin therapy in patients with non-Q wave MI or unstable angina pectoris. In clinical trials, the most common adverse events associated with lamifiban were bleeding complications which were increased by the concomitant administration of heparin.

Acetates↗

PubMed1999

Sibrafiban.

Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave MI or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with sibrafiban include bleeding, with minor haemorrhages occurring more often than with aspirin.

Animals↗

PubMed1999

Eptifibatide: a review of its use in patients with acute coronary syndromes and/or undergoing percutaneous coronary intervention.

UNLABELLED: Eptifibatide, a cyclic peptide, is a highly specific, intravenously administered glycoprotein (GP) IIb/IIIa receptor antagonist. By preventing fibrinogen binding to the GP IIb/IIIa receptor, eptifibatide inhibits platelet aggregation and prevents thrombus formation. Clinically, the drug is used as an adjunct to heparin and aspirin. The PURSUIT trial, conducted in >10,000 patients with unstable angina or non-Q-wave myocardial infarction (MI), showed that eptifibatide (180 microg/kg bolus then 2 microg/kg/min infusion for < or =72 hours) reduces the 30-day risk of death or nonfatal MI, with this benefit apparent at 96 hours. The absolute reduction in this end-point of 1.5% persisted at 6 months. The drug is effective in patients undergoing percutaneous coronary intervention (PCI), and, as shown in the North American subgroup, in patients in whom medical management is appropriate. Eptifibatide is also beneficial in patients undergoing PCI, whether or not they have unstable angina or non-Q-wave MI. In a dosage of 135 microg/kg then 0.5 microg/kg/min for 24 hours, eptifibatide reduced the 30-day risk of a combined end-point (death, nonfatal MI and urgent or emergency coronary interventions) by 2.5% (absolute reduction) in patients undergoing PCI in the IMPACT-II trial, when measured by per-protocol (patients treated), but not intent-to-treat, analysis. The drug also decreased the incidence of abrupt vessel closure and ischaemic cardiovascular complications in the first 24 hours (the period of greatest risk). Bleeding episodes are the most common adverse event associated with eptifibatide therapy. Although the incidence of major bleeding is increased with eptifibatide, most bleeding episodes are minor and occur at the vascular access site. The drug is not associated with an excess of intracranial bleeds, stroke or thrombocytopenia, does not appear to increase bleeding risk in patients undergoing coronary artery bypass graft (CABG), and does not cause antibody formation. Limited data suggest that eptifibatide may improve coronary flow when combined with alteplase in patients with acute Q-wave MI, but the possibility of increased bleeding with eptifibatide plus thrombolytics should be borne in mind. CONCLUSIONS: Intravenous eptifibatide, when combined with aspirin and heparin, reduces the 30-day risk of ischaemic events in patients with unstable angina and non-Q-wave MI and decreases ischaemic cardiovascular complications at the time of greatest risk in patients undergoing PCI. With its acceptable tolerability profile eptifibatide is a suitable option as a short term adjunct in these clinical settings. Whether eptifibatide in combination with fibrolysis may improve outcome in patients with acute Q-wave MI has yet to be determined.

Angina, Unstable↗

PubMed1999

Finasteride: an update of its use in the management of symptomatic benign prostatic hyperplasia.

UNLABELLED: Finasteride inhibits type 25alpha-reductase activity, significantly reducing dihydrotestosterone levels. Consequent reductions in prostate volume, increases in urinary flow rates and improvements in symptoms compared with placebo have been observed in trials of up to 4 years' duration and in noncomparative extensions (for up to 6 years). Results from the 4-year placebo-controlled PLESS trial show finasteride to significantly reduce the risk of benign prostatic hypertrophy (BPH)-related acute urinary retention and the requirement for surgical intervention. Finasteride has significantly greater efficacy in patients with a large prostate (> or = 40 ml) than in patients with a small prostate. However, the predictive value of prostate size has been questioned. Results of an earlier comparative 1-year trial show terazosin monotherapy and terazosin plus finasteride therapy to be significantly more effective than both finasteride monotherapy and placebo in reducing symptom scores and improving maximum urinary flow rates. Prostatic volume was significantly reduced by finasteride monotherapy and combination therapy only. The overall efficacy of finasteride in patients with mild to moderate symptomatic BPH tended to be greater than that of serenoa repens (Permixon) in a 6-month trial. A US cost analysis model indicates that finasteride and terazosin are less expensive than transurethral resection of the prostate (TURP) during the first 2 years of initiation. Canadian cost-effectiveness and cost-utility analyses using decision analysis modelling have shown primary intervention with finasteride to provide more quality-adjusted life years (QALYs) at lesser cost than watchful waiting or TURP in patients with moderate symptoms who receive the drug for < or = 3 years and < or = 14 years, respectively, but fewer QALYs at a higher cost in patients with severe symptoms needing therapy for > or = 4 years. Confirmatory prospective economic studies are required. Finasteride appears to improve overall quality of life to a similar extent to serenoa repens; patient satisfaction appears similar with finasteride and TURP. Finasteride is generally well tolerated. Most commonly reported adverse effects are sexually related (1 to 2.1 %). Gynaecomastia has been reported in 0.4% of patients. CONCLUSIONS: Despite modest improvements in maximum urinary flow rates and symptom scores, finasteride is a first-line treatment option in those with moderate uncomplicated BPH, especially in patients with a large prostate (> or = 40 ml). It is also an option in patients with more severe symptoms who are unable or unwilling to undergo surgery and in those awaiting surgery. Importantly, finasteride appears to reduce disease progression, significantly decreasing the incidence of acute urinary retention and the requirement for surgical intervention; to date, no other pharmacological agent has been shown to reduce these outcomes.

Controlled Clinical Trials as Topic↗

PubMed1999

Nebivolol in the management of essential hypertension: a review.

UNLABELLED: Nebivolol is a lipophilic beta1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol is administered as a racemic mixture of equal proportions of d- and l-enantiomers. The drug does not significantly influence glucose or plasma lipid metabolism and appears to have a protective effect on left ventricular function. At the recommended dosage (5 mg once daily) nebivolol reduces resting diastolic blood pressure as effectively as standard therapeutic dosages of atenolol, metoprolol, lisinopril and nifedipine, as shown in comparative trials. Nebivolol reduced blood pressure significantly more than enalapril 10 mg daily in the short but not the long term, although the enalapril dose may not have been optimal. Nebivolol has an additive effect in combination with hydrochlorothiazide. Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine. Nebivolol tended to prevent increases in early morning blood pressure better than nifedipine. Overall response rates to nebivolol therapy (a decrease in sitting/supine diastolic blood pressure to < or = 90 mm Hg or a 10% or > or = 10 mm Hg fall in diastolic blood pressure) ranged from 58 to 81% after 4 to 52 weeks' treatment. In comparative studies, response rates were greater in nebivolol than in enalapril or metoprolol recipients, but not significantly different from those in atenolol or nifedipine recipients. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with nebivolol. Comparative trials revealed no significant differences between the frequency and severity of adverse events in patients receiving nebivolol, atenolol, enalapril or placebo; however, the overall incidence of adverse events was greater with nifedipine or metoprolol. Some atenolol or enalapril, but not nebivolol, recipients reported impotence or decreased libido during therapy. CONCLUSION: Current evidence indicates that nebivolol 5 mg once daily is a well tolerated beta-blocker, which is as effective as once daily atenolol and other classes of antihypertensive agents. It may therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate uncomplicated essential hypertension.

Animals↗

PubMed1999

Diclofenac-potassium in migraine: a review.

UNLABELLED: The NSAID diclofenac is a potent inhibitor of prostaglandin synthesis and an established antipyretic and analgesic agent. Diclofenac-potassium was developed as an immediate-release tablet with the aim of providing rapid onset of action after oral administration. This formulation has been investigated in the acute treatment of migraine. Data from available placebo-controlled clinical trials indicate that diclofenac-potassium 50 or 100mg as an immediate-release tablet is more effective than placebo and as effective as oral sumatriptan 100mg and ergotamine plus caffeine at reducing pain intensity in patients with migraine 2 hours after initial administration. Duration of pain relief is similar for the 3 drugs but onset appears to be faster with diclofenac-potassium than with oral sumatriptan or ergotamine plus caffeine. Diclofenac-potassium appears to have favourable effects on some accompanying symptoms such as nausea and vomiting. The frequency of these symptoms was significantly lower with diclofenac-potassium than with sumatriptan in 1 study, although only a few patients had vomiting at baseline. Effects on phonophobia or photophobia did not differ between diclofenac-potassium, sumatriptan and ergotamine plus caffeine. The need for rescue medication is consistently less with diclofenac-potassium than with placebo. Data are inconsistent or scarce regarding the effects of diclofenac-potassium versus placebo on other measures such as headache recurrence and working ability. Diclofenac-potassium was generally well tolerated in clinical trials in patients with migraine. Adverse events reported most frequently (abdominal pain, tiredness and fatigue and nausea) were typically mild to moderate. CONCLUSION: Diclofenac-potassium provides rapid pain relief (within 60 to 90 minutes), is well tolerated and reduces the frequency of some of the accompanying symptoms in patients with migraine. Available trials indicate that diclofenac-potassium provides similar pain relief to sumatriptan and is at least as effective as ergotamine plus caffeine, but appears to have a greater effect on nausea and vomiting than sumatriptan and a faster onset of action than both drugs. Comparisons with other NSAIDs are lacking. Diclofenac-potassium is likely to find a role as a useful first-line option in the acute treatment of migraine.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Tranexamic acid: a review of its use in surgery and other indications.

UNLABELLED: Tranexamic acid is a synthetic derivative of the amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules. Intravenously administered tranexamic acid (most commonly 10 mg/kg followed by infusion of 1 mg/kg/hour) caused reductions relative to placebo of 29 to 54% in postoperative blood losses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), with statistically significant reductions in transfusion requirements in some studies. Tranexamic acid had similar efficacy to aprotinin 2 x 10(6) kallikrein inhibitory units (KIU) and was superior to dipyridamole in the reduction of postoperative blood losses. Transfusion requirements were reduced significantly by 43% with tranexamic acid and by 60% with aprotinin in 1 study. Meta-analysis of 60 trials showed tranexamic acid and aprotinin, unlike epsilon-aminocaproic acid (EACA) and desmopressin, to reduce significantly the number of patients requiring allogeneic blood transfusions after cardiac surgery with CPB. Tranexamic acid was associated with reductions relative to placebo in mortality of 5 to 54% in patients with upper gastrointestinal bleeding. Meta-analysis indicated a reduction of 40%. Reductions of 34 to 57.9% versus placebo or control in mean menstrual blood loss occurred during tranexamic acid therapy in women with menorrhagia; the drug has also been used to good effect in placental bleeding, postpartum haemorrhage and conisation of the cervix. Tranexamic acid significantly reduced mean blood losses after oral surgery in patients with haemophilia and was effective as a mouthwash in dental patients receiving oral anticoagulants. Reductions in blood loss were also obtained with the use of the drug in patients undergoing orthotopic liver transplantation or transurethral prostatic surgery, and rates of rebleeding were reduced in patients with traumatic hyphaema. Clinical benefit has also been reported with tranexamic acid in patients with hereditary angioneurotic oedema. Tranexamic acid is well tolerated; nausea and diarrhoea are the most common adverse events. Increased risk of thrombosis with the drug has not been demonstrated in clinical trials. CONCLUSIONS: Tranexamic acid is useful in a wide range of haemorrhagic conditions. The drug reduces postoperative blood losses and transfusion requirements in a number of types of surgery, with potential cost and tolerability advantages over aprotinin, and appears to reduce rates of mortality and urgent surgery in patients with upper gastrointestinal haemorrhage. Tranexamic acid reduces menstrual blood loss and is a possible alternative to surgery in menorrhagia, and has been used successfully to control bleeding in pregnancy.

Antifibrinolytic Agents↗

PubMed1999

Capecitabine.

Capecitabine is an orally administered fluoropyrimidine carbamate used for the treatment of paclitaxel- or anthracycline-refractory breast cancer. Capecitabine is metabolised via a 3-step process to the active agent fluorouracil. The final step of this process occurs preferentially in malignant tissue. In patients with paclitaxel-refractory breast cancer receiving capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) the objective tumour response rate was 20%. Disease progression occurred in 34% of patients and 40% had stable disease. In this trial, the median duration of response was 241 days. Disease progression or death occurred in 83% of patients, and median time to progression was 93 days. Median survival time was 384 days. In previously untreated patients with breast cancer, the response rate was higher and time to disease progression was longer after oral capecitabine (2510 mg/m2/day for 2 weeks of a 3-week cycle) than after intravenous cyclophosphamide, methotrexate and fluorouracil therapy. In clinical trials, generally gastrointestinal or haematological adverse events were reported most frequently. Other commonly reported events included hand-and-foot syndrome, fatigue, hyperbilirubinaemia, dermatitis and anorexia.

Animals↗

PubMed1999

Intranasal metoclopramide.

Intranasal metoclopramide is a new formulation of an established and effective antiemetic drug. Absorption after intranasal administration was lower than after oral or intravenous administration; otherwise the pharmacodynamic and pharmacokinetic profiles of the intranasal and parenteral formulations were similar. Intranasal and intramuscular metoclopramide showed similar efficacy in the control of acute emesis induced by moderately emetogenic chemotherapy in 12 patients. Intranasal metoclopramide 80mg significantly reduced the frequency of acute vomiting in 43 patients receiving highly emetogenic chemotherapy. A pilot study suggested that intranasal metoclopramide, with or without dexamethasone, may reduce cisplatin-induced delayed emesis. In a randomised crossover trial in 40 patients, intranasal metoclopramide or oral metoclopramide, both with dexamethasone, were equally effective in the control of delayed emesis induced by moderately-emetogenic chemotherapy. One 30 patient study suggests that intranasal metoclopramide has similar efficacy to oral metoclopramide in the treatment of functional dyspepsia. A non-significant trend to reducing postoperative nausea and vomiting has been seen in two trials of intranasal metoclopramide. Intranasal metoclopramide caused minor irritation of the nasal membrane and unpleasant taste in some patients, but was otherwise well tolerated. None of the more serious extrapyramidal effects sometimes associated with metoclopramide were reported.

Administration, Intranasal↗

PubMed1999

Extended-release dipyridamole/aspirin.

The fixed-dose combination of extended-release dipyridamole/aspirin (Aggrenox/Asasantin Retard) combines 2 antiplatelet agents with different mechanisms of action. The combination reduced thrombus formation in human and animal models. Coadministration of extended-release dipyridamole and aspirin in healthy volunteers had no significant effects on the plasma concentrations of either agent. Twice-daily oral extended-release dipyridamole/aspirin (400/50 mg/day) was twice as effective as either agent alone in the secondary prevention of stroke in a large clinical trial involving patients with prior stroke or transient ischaemic attack. The rate of the combined end-point of stroke and death tended to be lower with the combination than with other treatments. The incidence of death was not significantly reduced by any treatment. Most adverse events with extended-release dipyridamole/aspirin were mild and similar to those with either agent alone. Bleeding was more common with the combination than with extended-release dipyridamole alone, as was headache when compared with aspirin alone. Limited pharmacoeconomic analyses suggest that treatment with extended-release dipyridamole/aspirin was cost saving and was cost effective compared with aspirin monotherapy for the secondary prevention of stroke.

Animals↗

PubMed1999

Adefovir dipivoxil.

Adefovir dipivoxil is an ester prodrug of the nucleoside reverse transcriptase inhibitor adefovir (PMEA), the prototype compound of the acyclic nucleoside phosphonates. It has better oral bioavailability than the parent compound. Adefovir dipivoxil 120mg once daily significantly reduced viral load compared with placebo when added to standard antiretroviral therapy in a 6-month, double-blind study in patients with HIV infection. Viral suppression was maintained during an additional 6-month nonblind extension phase. The drug was most effective in patients with baseline isolates containing the M184V lamivudine resistance mutation according to data from a virological substudy of a large placebo-controlled trial. Adefovir dipivoxil 60mg was as effective as 120mg (both once daily) after 20 weeks' treatment in a randomised double-blind study in antiretroviral-experienced (protease inhibitor-naive) patients. Viral suppression was generally maintained in patients who developed new reverse transcriptase mutations during adefovir dipivoxil monotherapy or combination therapy for up to 12 months. No clear pattern of particular clinical resistance mutations has emerged. GI disturbances, hepatic effects and delayed renal abnormalities are the principal adverse events seen with adefovir dipivoxil. Reductions in serum free carnitine levels may occur and coadministration of L-carnitine is recommended.

Adenine↗

PubMed1999

Zanamivir: a review of its use in influenza.

UNLABELLED: Zanamivir is a novel inhibitor of the enzyme neuraminidase, a surface glycoprotein essential for the replication of type A and B influenza viruses. Statistically significant reductions in median time to alleviation of major symptoms of influenza were reported in phase II and III studies of zanamivir. Benefit was seen with early treatment (within 30 or 36 hours of onset of illness) in phase II trials. Median times to alleviation of major (or 'clinically significant') symptoms were reduced by 1 to 2.5 days after treatment with zanamivir 10 mg twice daily by oral inhalation for 5 days in 3 phase III studies. Benefit of zanamivir treatment in terms of time to return to normal activities and reductions in consumption of paracetamol (acetaminophen), and reductions in the level of interference of influenza with sleep, work, leisure and recreational activities, were reported. Reductions relative to placebo of 2.5 to 3.25 days were observed in median time to alleviation of major symptoms in high-risk patients. Available data also indicate potential of zanamivir in the prophylaxis of influenza. A statistically significant reduction in the incidence of influenza A was reported with zanamivir 10 mg by oral inhalation once daily for 4 weeks in a double-blind study in 1107 persons in 2 university communities. Prophylactic benefit of zanamivir in influenza A and B outbreaks has also been suggested by data from a nursing home community. Adverse event profiles in patients receiving zanamivir therapeutically or prophylactically appear similar to those in patients receiving placebo. The most commonly reported adverse events in therapeutic trials have been nasal signs and symptoms, diarrhoea, nausea, headache, bronchitis and cough. CONCLUSIONS: Prompt treatment with zanamivir in patients with naturally acquired influenza is associated with significant reductions in duration of symptomatic illness, accelerated return to normal levels of activity and reduced consumption of antibiotics for influenza-related complications. While vaccination in selected populations remains the seasonal intervention of choice for prophylaxis, the efficacy, good tolerability and lack of resistance seen with zanamivir are likely to make the drug a valuable treatment option, particularly in individuals not covered or inadequately protected by vaccination, and in those at high risk of influenza-related complications. Confirmation of the prophylactic efficacy of zanamivir would indicate a major potential role for the drug in this setting, especially in persons for whom vaccination is not suitable or fully effective, in closed communities (e.g. nursing homes) and in individuals at high risk.

Antiviral Agents↗

PubMed1999

Fibrin sealant: a review of its use in surgery and endoscopy.

UNLABELLED: Fibrin sealant (fibrin adhesive; fibrin glue; Beriplast P1) is a haemostatic and wound support product consisting of the blood coagulation factors fibrinogen, factor XIII and thrombin, the antifibrinolytic agent aprotinin and calcium chloride. Fibrin sealant has been used to good effect in a wide variety of surgical and endoscopic procedures. Suture support was provided in series of patients with oesophageal, gastric, colonic or rectal anastomoses, and fibrin sealant was as effective in haemostasis as microcrystalline collagen powder in hepatic surgery. It did not reduce postoperative peritoneal drainage after elective cholecystectomy, however. A 41% reduction (p<0.02) in incidence of air leakage was achieved when fibrin sealant was added to sutures in patients undergoing pulmonary resection in a randomised single-blind study. A high rate of complete remission of malignant pleural effusion has been reported after intrapleural instillation of fibrin sealant, and successful sealing of CSF leaks after trauma or surgery has also been achieved. Attenuation of prolonged or excessive haemorrhage after dental extraction has been achieved in patients on anticoagulant therapy or with haemorrhagic disorders who received fibrin sealant with packing and suturing. Repeated endoscopic injection of fibrin sealant was superior to single injection sclerotherapy with polidocanol 1% in a randomised study in 805 patients with bleeding peptic ulcers. Other data suggest that endoscopic injection of fibrin sealant is associated with lower recurrence of bleeding and need for emergency surgery than thrombin with adrenaline (epinephrine) or hypertonic saline with adrenaline. Similar haemostatic efficacy to laser photocoagulation or sclerotherapy was reported in a retrospective comparison. A statistically significant reduction relative to suturing in the incidence of wound dehiscence was reported after the use of fibrin sealant in cataract surgery, and benefit of the sealant has also been noted in patients receiving skin grafts and in those undergoing transurethral resection of the prostate gland. CONCLUSIONS: Although comparative studies would assist in the clarification of the place of the product discussed with respect to other haemostatic or wound support techniques and to other fibrin sealants, the formulation reviewed here has been shown overall to be effective and well tolerated in a variety of haemostatic and wound healing support roles in numerous types of surgery. Fibrin sealant has also been shown to be useful when administered endoscopically, with superiority over sclerotherapy being shown after repeated application in patients with peptic ulceration. Fibrin sealant can therefore be considered useful in a number of surgical and endoscopic settings.

Animals↗

PubMed1999

Olanzapine. A pharmacoeconomic review of its use in schizophrenia.

UNLABELLED: Olanzapine is an atypical antipsychotic agent which is at least as effective as the conventional agent haloperidol and the atypical agent risperidone. Olanzapine may be superior to haloperidol in some respects, including treatment of negative symptoms. A major advantage of olanzapine over haloperidol is its lower risk of extrapyramidal symptoms. Olanzapine improves quality of life and other aspects of functioning to a greater extent than haloperidol, and improves quality of life to at least the same extent as risperidone. However, olanzapine has a high acquisition cost compared with conventional antipsychotics. Despite this, most pharmacoeconomic analyses indicate that treatment with olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Total direct medical costs calculated from prospective resource utilisation data were lower with olanzapine than with haloperidol by $US388 (1995 values) per patient over 6 weeks and by $US55 per patient per month during 46 weeks extended treatment. In a mixed effects linear model of the same data, total costs over 1 year were $US10,301 (1996 values) per patient lower with olanzapine than haloperidol, and olanzapine was associated with 18.3 more symptom-free days per patient. Compared with risperidone, mean total direct medical costs over 28 weeks were $US493 (1995 values) per patient lower with olanzapine. In a Markov model of 5 years' treatment, olanzapine was associated with more time in a disability-free state than haloperidol at a total cost per patient that was lower by $US1539 (1995 values), 816 Pounds (1995/1996 values), 977 Dutch guilders (NLG; 1995 values) and 2296 Deutschmarks in US, UK, Dutch and German analyses, respectively. In a similar Spanish analysis, the overall total cost was higher with olanzapine, giving an incremental cost effectiveness for olanzapine of 32,516 pesetas (1995 values) per month of disability-free time gained. When risperidone was a comparator, the total cost per patient was $US1875 and NLG202 lower with olanzapine in US and Dutch analyses, respectively. CONCLUSIONS: The high acquisition cost of olanzapine is offset by reductions in other treatment costs in patients with schizophrenia. Compared with haloperidol, the drug improved patient outcome and quality of life, while overall direct treatment costs were generally not increased, or even decreased. Olanzapine has also been reported to decrease overall treatment costs compared with risperidone, but confirmation is required. Olanzapine is a cost-effective alternative to conventional agents for the treatment of moderately to severely ill patients with longstanding schizophrenia.

Antipsychotic Agents↗