Biomedical subjects

L R Wiseman

Publications and source records attributed to L R Wiseman.

At least 19 recordsLinked to original sources

PubMed1999

Basiliximab.

The chimaeric monoclonal antibody basiliximab specifically binds the alpha subunit of the interleukin-2 (IL-2) receptor on activated T lymphocytes. Through competitive antagonism of IL-2, basiliximab supplements standard immunosuppressive therapy after renal transplantation. < or =24 Hours after a single intravenous dose of basiliximab 2.5 to 25 mg, approximately 90% of available IL-2 receptors on T lymphocytes were complexed with the drug. This level of basiliximab binding was maintained for 4 to 6 weeks when renal transplant patients received basiliximab 20 mg 2 hours before and then 4 days after transplantation surgery. In 2 large, well-designed trials, the percentage of patients with biopsy-confirmed acute rejection episodes after renal transplantation was significantly lower with basiliximab 20 mg (administered 2 hours before and then 4 days after transplantation surgery; 30 or 33%, respectively) than placebo (44 or 46%) at 6 months after surgery. Basiliximab was well tolerated during clinical trials. The incidence of infections (including active cytomegalovirus infection) and post-transplant lymphoproliferative disorders was similar with basiliximab and placebo. Cytokine release syndrome was not observed in patients who received basiliximab.

Animals↗

PubMed1999

Moxifloxacin.

Moxilloxacin is a new fluoroquinolone antibacterial agent with a broad spectrum of activity, encompassing gram-negative and gram-positive bacteria. It has improved activity against gram-positive species (including staphylococci, streptococci, enterococci) and anaerobes compared with ciprofloxacin. This is offset by slightly lower activity against pseudomonal species and Enterobacteriaceae. In common with other fluoroquinolones, moxifloxacin attains good penetration into respiratory tissues and fluids and its bioavailability is substantially reduced by coadministration with an antacid or iron preparation. However, moxifloxacin does not interact with theophylline or warfarin. In clinical trials in patients with community-acquired pneumococcal pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) or acute sinusitis, moxifloxacin 400 mg once daily achieved bacteriological and/or clinical success rates of approximately 90% or higher. Moxifloxacin was as effective as amoxicillin 1 g 3 times daily and clarithromycin 500 mg twice daily in CAP and as effective as clarithromycin in AECB. In patients with sinusitis, a 7-day course of moxifloxacin 400mg once daily was as effective as a 10-day course of cefuroxime axetil 250mg twice daily. In contrast to some other fluoroquinolones, moxifloxacin appears to have a low propensity for causing phototoxic and CNS excitatory effects. The most common adverse events are gastrointestinal disturbances.

Anti-Infective Agents↗

PubMed1998

Midodrine. A review of its therapeutic use in the management of orthostatic hypotension.

Midodrine is a prodrug which undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration. Oral midodrine significantly increases 1-minute standing systolic blood pressure compared with placebo. The drug also improves standing time and energy level and clinical symptoms of orthostatic hypotension including dizziness, light-headedness and syncope. Comparative studies have shown midodrine to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension. Midodrine is well tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention and chills. The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime. Thus, oral midodrine is an effective therapeutic option for the management of various forms of orthostatic hypotension. This well-tolerated agent is likely to be useful in conjunction with standard nonpharmacological care.

Adrenergic alpha-Agonists↗

PubMed1998

Propionyl-L-carnitine.

Propionyl-L-carnitine stimulates energy production in ischaemic muscles by increasing citric acid cycle flux and stimulating pyruvate dehydrogenase activity. The free radical scavenging activity of the drug may also be beneficial. Propionyl-L-carnitine improves coagulative fibrinolytic homeostasis in vasal endothelium and positively affects blood viscosity. Improvements in maximum walking distance (MWD) correlated positively with increased mitochondrial oxidative adenosine triphosphate (ATP) synthesis in a study in patients with peripheral arterial disease. Oral propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD compared with placebo in patients with peripheral arterial obstructive disease (Fontaine Leriche stage II) in double-blind multicentre phase III studies (mean improvements ranged from 21 to 50% with placebo and from 33 to 73% with propionyl-L-carnitine). In one phase III study, propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD (measured by treadmill) compared with placebo (by 73 vs 46% after 24 weeks) in patients with intermittent claudication. Oral propionyl-L-carnitine therapy was associated with significant improvements in quality of life compared with placebo in patients with a baseline MWD < 250m. Propionyl-L-carnitine appears to be well tolerated, showing a similar incidence of adverse events to that reported in placebo recipients.

Aged↗

PubMed1998

Paclitaxel. An update of its use in the treatment of metastatic breast cancer and ovarian and other gynaecological cancers.

UNLABELLED: The antitumour agent paclitaxel has proved to be effective for the treatment of patients with metastatic breast or ovarian cancer, and limited data also indicate its clinical potential in patients with cervical or endometrial cancer. The regimen of paclitaxel administration has varied in clinical trials, the most common including a dosage of between 135 and 250 mg/m2 administered over an infusion period of 3 or 24 hours once every 3 weeks. Promising results have been achieved in phase I/II trials of a weekly regimen of paclitaxel (60 to 175 mg/m2). The objective response rate in patients with metastatic breast cancer (either pretreated or chemotherapy-naive) is generally between 20 and 35% with paclitaxel monotherapy, which compares well with that of other current treatment options including the anthracycline doxorubicin. Combination therapy with paclitaxel plus doxorubicin appears superior to treatment with either agent alone in terms of objective response rate and median duration of response. However, whether combination therapy also provides a survival advantage remains unclear; recent results of a phase III study indicate that it does not. Paclitaxel is also a useful second-line option in some patients with anthracycline-resistant disease. Combination therapy with paclitaxel and cisplatin has proved highly effective as first-line therapy for patients with advanced ovarian cancer, showing superior efficacy to cyclophosphamide/cisplatin in terms of progression-free survival time and median duration of survival. Combination therapy with paclitaxel and carboplatin has also shown promising results. Paclitaxel monotherapy is a useful second-line option for patients with platinum-refractory metastatic ovarian cancer (objective response rates have ranged from 15 to 48%). The major dose-limiting adverse events associated with paclitaxel include myelotoxicity and peripheral neuropathy. Paclitaxel has acceptable tolerability in most patients, although adverse events are common. CONCLUSION: Paclitaxel generally appears to be as effective as other antineoplastic agents used in the treatment of metastatic breast cancer, including doxorubicin. Importantly, it is a useful second-line option for some patients with anthracycline-resistant disease. Combination therapy with both paclitaxel and doxorubicin is a highly effective first-line option for metastatic breast cancer; however, recent results indicate no survival advantage versus monotherapy. Paclitaxel is a valuable agent for second-line treatment of patients with platinum-refractory metastatic ovarian cancer and, when combined with cisplatin or carboplatin, is recommended as first-line therapy for this disease.

Animals↗

PubMed1998

Anastrozole. A review of its use in the management of postmenopausal women with advanced breast cancer.

UNLABELLED: Anastrozole is a new oral nonsteroidal aromatase inhibitor indicated for the second-line endocrine treatment of postmenopausal women with advanced breast cancer. In postmenopausal women, anastrozole significantly reduces plasma estrogen levels; maximal suppression is achieved at dosages > or = 1 mg/day and levels remain suppressed during long term therapy. In two phase III clinical trials, anastrozole 1 or 10 mg/day showed similar clinical efficacy to that of oral megestrol (megestrol acetate) 160 mg/day in postmenopausal women with advanced breast cancer. Primary end-points [including time to disease progression (120 to 170 days) and overall response rates (complete and partial response and stable disease lasting > or = 24 weeks: 29 to 37%)] and secondary end-points [time to treatment failure (115 to 168 days) and duration of response (257 to 261 days)] did not differ significantly between treatment groups. However, a significant survival advantage was observed in patients treated with anastrozole 1 mg/day compared with megestrol in a follow-up combined analysis of patients enrolled in both studies (median time to death 26.7 vs 22.5 months). Quality of life parameters were generally improved to a similar extent in all treatment groups. Anastrozole is generally well tolerated in the majority of patients, the most common adverse events being gastrointestinal (GI) disturbances (incidence 29 to 33%). These events are generally mild or moderate and transient. Other adverse events reported with anastrozole include headache (< or = 18%), asthenia (< or = 16%), pain (< or = 15%), hot flushes and bone pain (both < or = 12%), back pain and dyspnoea (both < or = 11%) and peripheral oedema (< or = 9%). GI disturbance tended to be more common with anastrozole than megestrol, particularly at the 10 mg/day dosage; however, compared with megestrol, anastrozole is less frequently associated with weight gain. CONCLUSIONS: Anastrozole, with its apparent survival advantage versus megestrol (demonstrated in a combined analysis of phase III studies), convenient once daily oral administration and acceptable short term tolerability profile, is a second-line treatment option for postmenopausal patients with tamoxifenrefractory advanced breast cancer. The results of ongoing comparative trials with tamoxifen will determine the relative efficacy of anastrozole as first-line endocrine therapy for advanced breast cancer and as adjuvant therapy for early disease. In addition, direct comparative studies are required to determine the efficacy of anastrozole relative to that of other oral aromatase inhibitors such as letrozole and vorozole.

Anastrozole↗

PubMed1998

Cerivastatin.

Cerivastatin is a synthetic HMG-CoA reductase inhibitor with high liver selectivity, which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. In vitro, the affinity of cerivastatin for HMG-CoA reductase was higher than that of lovastatin, simvastatin and pravastatin. This higher enzyme affinity was reflected in vivo, with a lower ED50 (dose causing 50% inhibition) for cerivastatin in rats and beagle dogs compared with lovastatin. Cerivastatin 0.2 mg/day significantly reduced low density lipoprotein (LDL)-cholesterol, total cholesterol and triglyceride levels, and increased high density lipoprotein (HDL)-cholesterol levels, in patients with type IIa hypercholesterolaemia. Available data indicate that cerivastatin has a tolerability profile similar to that of other HMG-CoA reductase inhibitors. No drug interactions were observed when cerivastatin was coadministered with digoxin, warfarin, cimetidine or the antacid magnesium/aluminium hydroxide.

Animals↗

PubMed1998

Moexipril. A review of its use in the management of essential hypertension.

UNLABELLED: Moexipril is a prodrug which is hydrolysed after oral administration to its active metabolite moexiprilat, an inhibitor of the angiotensin converting enzyme (ACE). Once daily administration of moexipril 7.5 or 15 mg effectively reduces blood pressure in patients with essential hypertension (including the elderly and postmenopausal women with this condition). In double-blind randomised comparative studies, moexipril 7.5 to 15 mg once daily showed similar efficacy to other antihypertensive agents, including captopril, hydrochlorothiazide, atenolol, metoprolol, sustained release verapamil and nitrendipine. Combined therapy with hydrochlorothiazide and moexipril had a significantly greater antihypertensive effect than either agent alone. Moexipril is well tolerated by the majority of patients and compares well in this respect with other antihypertensive agents. Its tolerability profile appears to be characteristic of ACE inhibitors as a class (the most common adverse events being headache, symptoms of upper respiratory tract infection and cough). Moexipril generally had no clinically significant effect on lipid, glucose or electrolyte metabolism or haematological parameters, and, in particular, it was not associated with any significant changes in lipid or glucose metabolism in postmenopausal women (with or without hormone replacement therapy). CONCLUSIONS: Once daily moexipril is a useful agent for the treatment of essential hypertension, which compares well with currently available options in terms of clinical efficacy and tolerability. In addition, clinical experience to date supports its use in postmenopausal women.

Age Factors↗

PubMed1998

Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis.

UNLABELLED: Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR). CONCLUSION: Twice-daily intranasal azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.

Administration, Intranasal↗

PubMed1998

Dexrazoxane. A review of its use as a cardioprotective agent in patients receiving anthracycline-based chemotherapy.

UNLABELLED: Dexrazoxane has been used successfully to reduce cardiac toxicity in patients receiving anthracycline-based chemotherapy for cancer (predominantly women with advanced breast cancer). The drug is thought to reduce the cardiotoxic effects of anthracyclines by binding to free and bound iron, thereby reducing the formation of anthracycline-iron complexes and the subsequent generation of reactive oxygen species which are toxic to surrounding cardiac tissue. Clinical trials in women with advanced breast cancer have found that patients given dexrazoxane (about 30 minutes prior to anthracycline therapy; dexrazoxane to doxorubicin dosage ratio 20:1 or 10:1) have a significantly lower overall incidence of cardiac events than placebo recipients (14 or 15% vs 31%) when the drug is initiated at the same time as doxorubicin. Cardiac events included congestive heart failure (CHF), a significant reduction in left ventricular ejection fraction and/or a > or = 2-point increase in the Billingham biopsy score. These results are supported by the findings of studies which used control groups (patients who received only chemotherapy) for comparison. The drug appears to offer cardiac protection irrespective of pre-existing cardiac risk factors. In addition, cardiac protection has been shown in patients given the drug after receiving a cumulative doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that dexrazoxane does not affect the antitumour activity of doxorubicin: although most studies found that clinical end-points (including tumour response rates, time to disease progression and survival duration) did not differ significantly between treatment groups, the largest study did show a significant reduction in response rates in dexrazoxane versus placebo recipients. Dexrazoxane permits the administration of doxorubicin beyond standard cumulative doses; however, it is unclear whether this will translate into prolonged survival. Preliminary results (from small nonblind studies) indicate that dexrazoxane reduces cardiac toxicity in children and adolescents receiving anthracycline-based therapy for a range of malignancies. The long term benefits with regard to prevention of late-onset cardiac toxicity remain unclear. With the exception of severe leucopenia [Eastern Cooperative Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and nonhaematological adverse events appears similar in patients given dexrazoxane to that in placebo recipients undergoing anthracycline-based chemotherapy. Although preliminary pharmacoeconomic analyses have shown dexrazoxane to be a cost-effective agent in women with advanced breast cancer, they require confirmation. CONCLUSIONS: Dexrazoxane is a valuable drug for protecting against cardiac toxicity in patients receiving anthracycline-based chemotherapy. Whether it offers protection against late-onset cardiac toxicity in patients who received anthracycline-based chemotherapy in childhood or adolescence remains to be determined. Further clinical experience is required to confirm that it does not adversely affect clinical outcome, that it is a cost-effective option, and to determine the optimal treatment regimen.

Animals↗

PubMed1998

Abciximab. An updated review of its use in ischaemic heart disease.

UNLABELLED: Abciximab is a glycoprotein IIb/IIIa receptor antagonist that has proven to be of significant clinical value in improving patient outcome after percutaneous coronary revascularisation. Primarily, the drug inhibits platelet aggregation, but it may also have anticoagulant activity and other beneficial effects, such as inhibiting migration and promoting apoptosis of smooth muscle cells. Large well designed studies have found administration of abciximab (as an adjunct to heparin and aspirin) during percutaneous coronary revascularisation to significantly reduce the incidence of ischaemic complications occurring in the 30 days after the procedure. Significant benefit, particularly on the incidence of myocardial infarction, was still evident after 6 months in 2 of 4 major trials. Abciximab provides particular benefit in patients with unstable angina or myocardial infarction who are undergoing percutaneous coronary revascularisation. The benefits of the drug are additive to those achieved with coronary stenting. Very preliminary data suggest that abciximab may improve coronary blood flow after myocardial infarction and allow reperfusion to be achieved with reduced thrombolytic doses. Caution is required to minimise the risk of bleeding complications with the use of abciximab in combination with heparin and aspirin. Careful patient selection, use of an appropriate heparin regimen, early vascular sheath removal and meticulous femoral artery access site care are recommended. Thrombocytopenia can occur with abciximab treatment, but severe cases are uncommon (< 2% of patients) and can be treated with platelet transfusions. The high acquisition cost of abciximab may be partly or fully offset by the costs averted by the reduced incidence of ischaemic complications and need for urgent and/or repeat revascularisation in high risk patients who receive the drug. However, if bleeding complications occur, this adds to treatment costs. Cost effectiveness analyses generally support the use of abciximab in high risk patients. CONCLUSIONS: Abciximab can be recommended for the prevention of acute ischaemic events in most patients undergoing percutaneous coronary revascularisation, but careful patient selection and strict adherence to the recommended treatment protocol are required to reduce the risk of bleeding complications and thrombocytopenia. Its use in high risk patients is largely supported by pharmacoeconomic data. Further pharmacoeconomic information is needed to establish the drug as a standard of care for all patient groups. The indications for abciximab are likely to expand as more data on its use in acute coronary syndromes become available.

Abciximab↗

PubMed1998

Topotecan. A review of its potential in advanced ovarian cancer.

The topoisomerase I inhibitor topotecan has shown antitumour activity against a variety of tumour types in vitro and in vivo. Topotecan in combination with drugs that induce DNA damage generally results in synergistic killing of tumour cells in vitro. As the activity of topotecan is related to exposure time, the drug is administered by intravenous infusion either continuously or once daily over a 30-minute period for several consecutive days. A 30-minute infusion of topotecan 1.5 mg/m2 on 5 consecutive days every 3 weeks produced response rates of up to approximately 20% in patients with advanced ovarian cancer who had failed to respond to platinum-based regimens or relapsed after initial response to such regimens. No significant differences in efficacy were apparent between topotecan and paclitaxel in a phase III study in patients with recurrent ovarian cancer, although a trend in favour of topotecan was evident for all major efficacy parameters. Non-cumulative myelosuppression, including neutropenia, thrombocytopenia and anaemia, is the dose-limiting toxicity associated with topotecan. Myelo-suppression was significantly more common with topotecan than with paclitaxel in a single comparative study. Non-haematological adverse events in topotecan recipients are generally mild and include alopecia, nausea, vomiting, and other gastrointestinal problems. Thus, topotecan has modest efficacy in the treatment of recurrent advanced ovarian cancer, with clinical activity similar to that of paclitaxel in a large randomised phase III study in this setting. Combinations of paclitaxel and a platinum compound are being used increasingly for first-line therapy, although relapse rates remain significant. Topotecan is therefore a suitable second-line option, providing antitumour response for some patients whose disease has relapsed after, or is refractory to, platinum-based therapy. Its wider potential when used either alone or in combination regimens should become clearer from ongoing studies.

Antineoplastic Agents↗

PubMed1998

Pexiganan acetate.

Pexiganan acetate (MSI 78) is a synthetic cationic peptide (22 amino acids) with antibacterial activity. It is an analogue of magainin 2, which is a host defence peptide isolated from frog skin. The drug is thought to act by disturbing the permeability of the cell membrane or cell wall. Pexiganan acetate has good in vitro activity against Gram-positive and Gram-negative aerobes; 99% of strains were susceptible to the agent using a break-point of 64 mg/L. 89 to 97% of anaerobes were susceptible to pexiganan acetate using the same break-point. After 7 passages in vitro, there was no evidence of resistance to pexiganan acetate among 2 strains of Staphylococcus aureus. In 2 phase III multicentre randomised double-blind trials in diabetic patients with infected foot ulcers, both topical pexiganan acetate 1% and oral ofloxacin 800 mg/day achieved clinical cure or improvement in about 90% of patients. Eradication of pathogens in the 2 studies was achieved in 82% of ofloxacin recipients and 66% of pexiganan acetate recipients at the end of therapy. Limited data indicate that pexiganan acetate is well tolerated.

Administration, Topical↗

PubMed1997

Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer.

The antineoplastic agent mitoxantrone in combination with a corticosteroid (either prednisone or hydrocortisone) has shown clinical efficacy as palliative treatment for a proportion of patients (about 35 to 40%) with hormone-resistant advanced prostate cancer, a disease which predominantly affects elderly men and for which few systemic treatment options are available. Palliative end-points including pain relief, decreased analgesic use and reduced prostate specific antigen levels (a marker of tumour response) are reached in a greater percentage of patients receiving combination therapy than corticosteroid alone. In addition, there are generally greater improvements in quality-of-life parameters in mitoxantrone recipients. However, combined treatment offers no survival advantage over corticosteroid monotherapy. Neutropenia is the most common toxicity associated with mitoxantone therapy and may necessitate dosage reduction in some patients. Otherwise, mitoxantrone generally has a more favourable tolerability profile than has been established for other cytotoxic agents such as doxorubicin with regard to acute adverse events (e.g. nausea/vomiting, anorexia, constipation, alopecia, malaise/ fatigue, oedema) and cardiac toxicity. In conclusion, administration of mitoxantrone plus a corticosteroid can provide palliation for some elderly patients with hormone-resistant advanced prostate cancer, and is thus a valuable first-line treatment for this indication.

Antineoplastic Agents↗

PubMed1997

Vorozole.

Vorozole is a triazole derivative which binds to the cytochrome P450 moiety of aromatase, thus causing reversible inhibition of the enzyme. Plasma estradiol levels are reduced by about 90% in postmenopausal women treated with vorozole. Phase II clinical studies found vorozole to be an effective agent for the treatment of postmenopausal women with advanced breast cancer, achieving objective responses in up to 35% of patients. In 2 large phase III studies, vorozole 2.5 mg/day demonstrated favourable clinical efficacy compared with aminoglutethimide and megestrol. Vorozole improved patients' quality of life to a greater extent than aminoglutethimide. Clinical trials to date indicate that the tolerability of vorozole is better than that of aminoglutethimide. Vorozole also appears to be at least as well tolerated as megestrol (although inappropriate bodyweight gain is more common in megestrol recipients). The most common adverse events with vorozole are hot flushes, and nausea, which are generally mild in severity.

Anastrozole↗

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

Cefpirome. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy in the treatment of severe nosocomial infections and febrile neutropenia.

Cefpirome is an injectable extended-spectrum or 'fourth generation' cephalosporin. Its antibacterial activity encompasses many of the pathogens involved in hospital-acquired infections such as Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, coagulase-negative staphylococci and viridans group streptococci. Cefpirome also has in vitro activity against Streptococcus pneumoniae regardless of penicillin susceptibility. It is stable against most plasmid- and chromosome-mediated beta-lactamases, with the exception of the extended-spectrum plasmid-mediated SHV enzymes. Intravenous cefpirome 2g twice daily has shown clinical efficacy comparable to that of ceftazidime 2g 3 times daily in the treatment of hospitalised patients with moderate to severe infections. Clinical response and bacteriological eradication rates were similar in patients with severe pneumonia or septicaemia treated with either cefpirome or ceftazidime. Cefpirome appeared more effective than ceftazidime in the eradication of bacteria in patients with febrile neutropenia in 1 study; however, clinical response rates were similar in the 2 treatment groups. The tolerability of cefpirome appears similar to that of ceftazidime and other third generation cephalosporins, diarrhoea being the most frequently observed event. Thus, cefpirome is likely to be a valuable extended-spectrum agent for the treatment of severe infections. Cefpirome offers improved coverage against some Gram-positive pathogens and Enterobacteriaceae producing class I beta-lactamases compared with the third generation cephalosporins, although this has yet to be demonstrated in clinical trials.

Animals↗

PubMed1997

Toremifene. A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer.

The triphenylethylene antiestrogen toremifene is a chlorinated derivative of the antiestrogen tamoxifen, an agent which has been widely and successfully used in the treatment of breast cancer. Clinical trials investigating the efficacy of toremifene as first-line endocrine therapy in postmenopausal women with advanced breast cancer (estrogen receptor status positive or unknown) have shown this drug to have similar antitumour activity to that of tamoxifen. In multicentre comparative trials, objective responses (complete and partial) occurred in 20 to 29% of patients treated with toremifene (60 to 240 mg/day) and in 19 to 37.5% of tamoxifen (20 or 40 mg/day) recipients. The duration of response, time to disease progression and median overall survival time were generally similar in both treatment groups. Toremifene is well tolerated. Most drug-related adverse effects are mild or moderate in severity and rarely necessitate discontinuation of therapy. The tolerability profile of toremifene is similar to that reported for tamoxifen, the most common adverse effects being hot flushes, sweating, nausea and/or vomiting, dizziness, oedema, and vaginal discharge and/or bleeding. Thus, toremifene provides an equally effective and well tolerated alternative to tamoxifen for the first-line endocrine therapy of postmenopausal advanced breast cancer. Preclinical studies showing toremifene to have a lower carcinogenic potential than tamoxifen indicate that toremifene may be a preferable agent for long term treatment regimens; however, these findings require confirmation in the clinical setting.

Animals↗