Biomedical subjects

H M Lamb

Publications and source records attributed to H M Lamb.

At least 19 recordsLinked to original sources

PubMed2001

Rivastigmine. A pharmacoeconomic review of its use in Alzheimer's disease.

UNLABELLED: Alzheimer's disease is associated with a large cost burden, of which institutionalised care constitutes a major component. Therefore, the decision to move a patient from the community to institutionalised care is associated with a significant increase in direct costs. About three-quarters of patients with Alzheimer's disease are admitted to a nursing home within 5 years of diagnosis. Unpaid or informal caregiver time is another large cost in Alzheimer's disease, especially for patients cared for in the community; informal care can account for up to three-quarters of healthcare costs in non-institutionalised patients. Several cholinesterase inhibitors, of which rivastigmine is one, are available for the treatment of patients with mild to moderate Alzheimer's disease. By improving cognitive function and slowing the rate of cognitive decline, cholinesterase inhibitor therapy may reduce a significant part of the economic burden of the disease by delaying the move to institutionalised care. In the absence of prospective long term data which focus on pharmacoeconomic end-points, modelling techniques have been used to extrapolate clinical data available for some cholinesterase inhibitors, including rivastigmine. Four economic analyses, based on a single model of cognitive decline, have been performed with rivastigmine from the perspective of the provider or society. All show that rivastigmine therapy (excluding drug-related costs) is associated with cost savings in patients with mild to moderate Alzheimer's disease by delaying the time to institutionalisation. If the acquisition cost of the drug was factored in, the cost savings completely or partially offset treatment costs. The magnitude of the cost savings increased as the time horizon increased (up to 2 years). The largest savings were realised in patients with mild disease over a 2-year time-frame, suggesting that treatment should be initiated early from an economic viewpoint. Pharmacoeonomic data comparing different cholinesterase inhibitors are, as yet, unavailable. CONCLUSION: Pharmacoeconomic analyses, based on modelled data excluding drug costs, indicate that rivastigmine completely or partially offsets the costs of treatment by delaying cognitive decline and the time to institutionalisation in patients with mild to moderate Alzheimer's disease. From a societal perspective, cost savings are realised if the drug is introduced early in the disease. Additional benefits offered by rivastigmine on behavioural symptoms, which may reduce caregiver burden, have yet to be investigated from a pharmacoeconomic perspective.

Activities of Daily Living↗

PubMed2000

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

Donepezil (E-2020) is a reversible, noncompetitive, piperidine-type cholinesterase inhibitor. It is selective for acetylcholinesterase rather than butyrylcholinesterase. Donepezil 5 and 10 mg/day significantly improved cognition and global clinical function compared with placebo in well designed short term trials (14 to 30 weeks) in 161 to 818 patients with mild to moderate Alzheimer's disease. Beneficial effects on cognition were observed from week 3 of treatment. Donepezil 10 mg/day significantly delayed the deterioration in activities of daily living (ADL) [by 55 weeks] compared with placebo in a retrospective analysis of 1 trial, and in the largest trial significantly improved patients' abilities to perform complex tasks. However, no significant improvement in function was observed with donepezil 5 mg/day in another trial. In the 2 trials of longest duration donepezil (5 and 10 mg) significantly delayed symptomatic progression of the disease. While there was no evidence for a positive effect of donepezil on patients' quality of life, there are no validated measures of this parameter specific to patients with Alzheimer's disease. Donepezil (5 and 10 mg) significantly reduced caregiver burden. Long term efficacy data suggest that improvements in cognition, global function or ADL are maintained for about 21 to 81 weeks with donepezil (10 mg/day in most patients). Donepezil is generally well tolerated with the majority of adverse events being mild and transient. Predictably, most events were cholinergic in nature and generally related to the gastrointestinal and nervous systems. The incidence of these events was significantly higher with donepezil 10 mg than with placebo in short term clinical trials; however, this may have been due to the 7-day dose increase schedule used in these studies and can be minimised by increasing the dose after a longer (6-week) period. The incidence of serious adverse events was generally similar between donepezil 5 and 10 mg (4 to 10%) and placebo (5 to 9%) in short term trials. 26% of patients receiving donepezil (5 and 10 mg) reported serious events over a 98-week period in a long term trial. Importantly, there was no evidence of hepatotoxicity with this drug. Conclusions. Donepezil (5 and 10 mg) is an agent with a simple once-daily dosage schedule which improves cognition and global clinical function in the short (up to 24 weeks) and long term (up to about 1 year) in patients with mild to moderate Alzheimer's disease. Improvements in ADL were also observed with donepezil 10 mg/day. Adverse events associated with donepezil are mainly cholinergic. Donepezil has been extensively studied and should be considered as a first-line treatment in patients with mild to moderate Alzheimer's disease.

Aged↗

PubMed2000

Moxifloxacin: a review of its clinical potential in the management of community-acquired respiratory tract infections.

UNLABELLED: Moxifloxacin is an extended-spectrum fluoroquinolone which has improved coverage against gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, while retaining good activity against gram-negative bacteria. The antibacterial spectrum of moxifloxacin includes all major upper and lower respiratory tract pathogens; it is one of the most active fluoroquinolones against pneumococci, including penicillin- and macrolide-resistant strains. In in vitro studies, emergence of bacterial resistance was less common with moxifloxacin than with some other fluoroquinolones, but this requires confirmation in large-scale clinical studies. As with other fluoroquinolones, moxifloxacin achieves good penetration into respiratory tissues and fluids. It shows a low potential for drug interactions and dosage adjustment is not required for patients of advanced age or those with renal or mild hepatic impairment. The efficacy of oral moxifloxacin has been demonstrated in large, well-designed clinical trials in patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Moxifloxacin 400 mg once daily achieved bacteriological and clinical success rates of approximately 90% or higher. It was as effective as, or more effective than, comparators including clarithromycin, cefuroxime axetil and high dose amoxicillin in these trials. The most commonly reported adverse events in patients receiving moxifloxacin are gastrointestinal disturbances. Moxifloxacin is also associated with QTc prolongation in some patients; there are, as yet, no data concerning the possible clinical sequelae of this effect in high-risk patients. Moxifloxacin has a low propensity for causing phototoxic reactions relative to other fluoroquinolones, and animal data suggest that it has a low potential for causing excitatory CNS and hepatotoxic effects. CONCLUSIONS: As an extended-spectrum fluoroquinolone, moxifloxacin offers the benefits of excellent activity against pneumococci, once daily administration and a low propensity for drug interactions. Although studies are needed regarding its tolerability in at-risk patients with QT interval prolongation, available data suggest that moxifloxacin is likely to become a first-line therapy option for the treatment of community-acquired lower respiratory tract infections, particularly in areas where drug-resistant S. pneumoniae or H. influenzae are common.

Anti-Infective Agents↗

PubMed2000

Lidocaine patch 5%.

Lidocaine patch 5% comprises a soft, stretchy adhesive patch (l0 by 14 cm) containing 5% lidocaine (700 mg) for the topical treatment of pain associated with postherpetic neuralgia (PHN). Lidocaine provides analgesic relief by blocking neuronal sodium channels. In clinical trials (conducted over 12 hours to 24 days) involving patients with allodynia associated with PHN, treatment with lidocaine patch 5% resulted in a significant reduction in pain intensity and increased pain relief compared with vehicle patch. Lidocaine patch 5% was associated with few adverse events, the most frequent being mild skin redness or irritation at the application site which occurred with a similar incidence with lidocaine and vehicle patch.

Absorption↗

PubMed2000

Insulin glargine.

Insulin glargine is an extended-action biosynthetic human insulin. It precipitates in the neutral environment of subcutaneous tissue and is thus gradually absorbed into the bloodstream. The addition of small amounts of zinc to the formulation further delays absorption. In small euglycaemic clamp studies, the onset of action of insulin glargine was shown to be later, the duration of action longer and the time-action profile flatter than that of Neutral Protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus and healthy volunteers. Four large clinical trials of up to 28 weeks' duration have shown that a single bedtime dose of insulin glargine, in combination with preprandial short-acting insulin, is as effective or more effective than once or twice daily NPH plus short-acting insulin in improving glycaemic control in patients with type 1 diabetes mellitus. In 3 large comparative trials, insulin glargine decreased glycosylated haemoglobin and/or fasting blood glucose levels to a similar extent to that seen with NPH insulin in patients with insulin-dependent or non-insulin-dependent type 2 diabetes mellitus, either as monotherapy or in combination with oral hypoglycaemic agents. Insulin glargine appears to be well tolerated. A lower incidence of hypoglycaemia, especially at night, was reported in most trials with insulin glargine when compared with NPH insulin.

Blood Glucose↗

PubMed2000

Meropenem: a review of its use in patients in intensive care.

UNLABELLED: Meropenem is a carbapenem antibacterial agent that has antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms. In vitro studies involving isolates from patients in intensive care units (ICUs) indicate that meropenem is more active against most gram-negative pathogens than other comparators (including imipenem), although, compared with imipenem, meropenem is less active against most gram-positive organisms. Resistance to meropenem is uncommon in most bacteria. Treatment with meropenem as initial empirical monotherapy was effective in a range of serious infections in adult and paediatric ICU patients. Meropenem monotherapy was as effective as imipenem/cilastatin in 4 comparative trials in terms of satisfactory clinical and bacteriological responses. Meropenem monotherapy was significantly more effective than ceftazidime-based combination treatments in 2 trials in patients with nosocomial lower respiratory tract infections (LRTIs) in terms of both clinical and bacteriological responses. Meropenem was also more active than ceftazidime-based treatments against both gram-positive and gram-negative organisms. However, 2 studies in patients with a range of serious infections found no significant differences between meropenem and cephalosporin-based treatments in terms of clinical or bacteriological response. Meropenem was also as effective as cephalosporin-based treatments in comparative trials in children with serious infections. Meropenem is well tolerated as either a bolus or an infusion, and clinical trials have shown similar incidences of adverse events to those observed with cephalosporin-based treatments. It is well tolerated by the CNS, with seizures reported infrequently, and can therefore be used at high doses and in patients with meningitis. The incidence of drug-related nausea and vomiting is low and, in contrast to imipenem/cilastatin, does not increase with dose or speed of administration. CONCLUSIONS: Meropenem is a well tolerated broad spectrum antibacterial agent that, when used as initial empirical monotherapy, is as effective as imipenem/cilastatin in the treatment of a range of serious infections (including nosocomial) in adults and children in ICUs. Compared with cephalosporin-based combination treatments, meropenem monotherapy may be more effective in the treatment of nosocomial LRTIs and can be used as monotherapy. Meropenem has an important role in the empirical treatment of serious infections in adults and children in ICUs.

Adult↗

PubMed2000

Gemifloxacin.

Gemifloxacin is a fluoroquinolone antibacterial agent which has an enhanced affinity for topoisomerase i.v.. It has potent activity against most Gram-positive bacteria, particularly Streptococcus pneumoniae. Gemifloxacin is over 30-fold more active than ciprofloxacin and 4- to 8-fold more active than moxifloxacin against this pathogen. Gemifloxacin has excellent activity against Haemophilus influenzae and Moraxella catarrhalis, and is unaffected by beta-lactamase production. It is generally 2-fold less active than ciprofloxacin against most Enterobacteriaceae. Atypical respiratory pathogens (Legionella, Mycoplasma and Chlamydia spp.) are highly susceptible to gemifloxacin. Preliminary results from phase II trials show that oral gemifloxacin 320 mg/day produced bacteriological responses of 94.7% in patients with acute exacerbations of chronic bronchitis and 95% of patients with uncomplicated urinary tract infections. Adverse events included nausea, abdominal pain, headache and mild rash in patients and healthy volunteers treated with gemifloxacin 320 mg/day. Gemifloxacin has a low potential for mild phototoxicity (comparable to that of ciprofloxacin).

Anti-Infective Agents↗

PubMed2000

Exemestane: a review of its use in postmenopausal women with advanced breast cancer.

UNLABELLED: Exemestane is an orally active irreversible steroidal aromatase inactivator that effectively suppresses in vivo aromatase activity and circulating estrogen levels in postmenopausal women with advanced breast cancer. In clinical trials, tumour responses were elicited by exemestane regardless of disease site, importantly, in patients with visceral disease. In patients with disease refractory to tamoxifen, once daily exemestane 25 mg produced objective response rates of 15 to 28% that were sustained for a median duration of 69 to 76 weeks. In a large comparative study, exemestane and megestrol showed similar clinical efficacy according to objective response and overall success rates. However, the duration of overall success and times to disease progression and treatment failure were significantly prolonged with exemestane compared with megestrol. Additionally, a significant survival advantage for exemestane over megestrol was reported. Exemestane retains efficacy in patients refractory to multiple hormonal therapies. In patients whose disease had progressed after tamoxifen and megestrol, objective response rates of 11 and 13% were reported, and responses were similar regardless of whether megestrol resistance was de novo or acquired. Objective responses also occurred in studies that explored sequential use of exemestane after failure of aminoglutethimide (26% with exemestane 200 mg/day) or other nonsteroidal aromatase inhibitors (6.6% with exemestane 25 mg/day). Additionally, tumour responses (objective response 6.1%, overall success rate 24.7%) were reported in patients who had not responded to their last hormonal treatment. As first-line treatment, once daily exemestane 25 mg elicited objective and overall success rates of 42 and 58%, compared with 16 and 31% for once daily tamoxifen 20 mg. Exemestane was generally well tolerated in clinical trials at once daily dosages up to 600 mg. At the 25 mg recommended once daily dosage, the most commonly occurring adverse events were nausea, hot flushes, fatigue, increased sweating and dizziness. Weight gain occurred in significantly more patients receiving megestrol than among those treated with exemestane. Androgenic events have been reported in a small number of patients receiving once daily exemestane 200 mg, but were rarely reported at the recommended dosage. CONCLUSIONS: Exemestane is effective in postmenopausal patients with tamoxifen-refractory advanced breast cancer, prolonging time to disease progression and treatment failure and improving survival compared with megestrol treatment. Moreover, exemestane has an acceptable tolerability profile and a convenient once daily oral dosage regimen. Available data indicate that exemestane maintains its efficacy in patients with visceral metastases and does not show cross-resistance with nonsteroidal aromatase inhibitors. Preliminary data indicate that exemestane is also effective as first-line therapy for advanced breast cancer.

Androstadienes↗

PubMed2000

Infliximab: a review of its use in the management of rheumatoid arthritis.

UNLABELLED: Infliximab is a chimaeric monoclonal antibody to human tumour necrosis factor-alpha (TNFalpha). It binds to both soluble and transmembrane forms of TNFalpha at picomolar concentrations in vitro. Secondary to inhibition of TNFalpha, infliximab reduces serum levels of inflammatory mediators and vascular endothelial growth factor, decreases the expression of chemokines in the synovial tissue and reduces lymphocyte migration into the joints of patients with rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted over 26 and 30 weeks, infliximab plus methotrexate was significantly more effective than placebo plus methotrexate according to American College of Rheumatology response criteria in patients with active rheumatoid arthritis. A substantial response to infliximab-containing regimens was evident within 2 weeks. Extension phases of these studies indicate sustained clinical efficacy for up to 54 weeks. Of considerable importance are preliminary 1-year radiographic findings that show zero median progression of joint damage in infliximab plus methotrexate recipients compared with a 7 to 8% deterioration in placebo plus methotrexate recipients. Headache, nausea, upper respiratory tract infection and infusion-related reactions are the most commonly reported adverse events with infliximab. Serious events occurred in 4.4% of infliximab versus 1.8% of placebo recipients. In the largest clinical trial, 2 patients died from disseminated infection and 3 developed new or recurrent malignancies, although the exact relationship between infliximab and these events is unknown. To date, 2 patients with rheumatoid arthritis have developed drug-induced lupus. About 10% of patients may develop antibodies to infliximab, although the clinical significance of these is presently unknown. CONCLUSION: Infliximab represents an important advance in the treatment of rheumatoid arthritis, with tolerability concerns raised by early studies having been eased somewhat by more recent data in larger patient numbers. If preliminary results indicating that infliximab is able to arrest joint destruction in patients with rheumatoid arthritis are corroborated, the drug will likely become an integral component of future management strategies for this difficult-to-treat condition.

Antibodies, Monoclonal↗

PubMed2000

Meropenem: an updated review of its use in the management of intra-abdominal infections.

UNLABELLED: Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity which encompasses gram-negative, gram-positive and anaerobic bacteria. Like other carbapenems, meropenem is stable against chromosomal and extended-spectrum beta-lactamases. In patients with moderate to severe intra-abdominal infections, empirical monotherapy with meropenem achieved clinical response rates ranging from 91 to 100% in 7 randomised comparative trials. Efficacy rates were similar to those of imipenem/cilastatin (94 to 97%), clindamycin plus tobramycin (93%) and, overall, to cefotaxime plus metronidazole (75 to 100%), although there were differences between trials versus this combination regimen. According to limited data, meropenem also achieved clinical response rates of over 80% in patients with severe intra-abdominal infections. Meropenem is well tolerated, the most common adverse events being diarrhoea, rash, nausea/vomiting and inflammation at the injection site which are reported in <2.5% of patients each. Meropenem also has an improved CNS tolerability profile compared with imipenem/cilastatin. CONCLUSIONS: Extensive comparative clinical data demonstrate that meropenem can be used effectively as empirical monotherapy in moderate to severe intra-abdominal infections. It also shows potential in the most severe forms of infection, although experience in this infection type remains limited. Compared with standard combination regimens, meropenem offers the benefits of ease of administration without the need for monitoring. It also offers improved CNS tolerability compared with imipenem/cilastatin with the option of a higher maximum dosage, which may be a particular advantage in patients with severe intra-abdominal infections.

Abdomen↗

PubMed2000

Inhaled fluticasone propionate. A pharmacoeconomic review of its use in the management of asthma.

UNLABELLED: Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease. CONCLUSIONS: In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.

Administration, Inhalation↗

PubMed1999

Valrubicin.

Valrubicin (AD-32) is an N-trifluoroacetyl, 14-valerate derivative of the anthracycline doxorubicin. It has antineoplastic activity which probably results from interference with nucleic acid metabolism by the drug. Valrubicin entered individual cells more rapidly than doxorubicin in vitro. When valrubicin was administered intravesically to patients with bladder cancer, cytotoxic concentrations of the drug penetrated the superficial muscle layer of the bladder. Complete response rates were 18 and 29% in patients with carcinoma in situ of the bladder which was refractory to intravesical BCG in 2 non-comparative trials of prophylactic intravesical valrubicin. In patients with recurrent superficial papillary tumours, the complete response rate was 46%. Adverse events were generally transient in patients who received intravesical valrubicin. Bladder irritation occurred in 88% of patients. Systemic absorption of intravesically administered valrubicin was minimal. Accordingly, systemic adverse events generally occurred in < or =5% of patients. Valrubicin was less toxic to chick embryos and haematopoietic stem cells in vitro and produced a lower incidence of cardiotoxicity in rabbits, compared with doxorubicin.

Administration, Intravesical↗

PubMed1999

Rituximab.

Rituximab is a chimaeric monoclonal antibody which specifically binds to the CD20 antigen on normal and malignant B lymphocytes. It produces antibody-dependent cell- and complement-mediated cytotoxicity in these cells. Rituximab reduced peripheral B lymphocyte counts by approximately 90% within 3 days in patients with relapsed indolent lymphoma. Counts remained depleted for 6 months and recovered by months 9 to 12 after 4 doses of rituximab 375 mg/m2 once weekly. Clinical response rates were 46 and 48% in 2 non-comparative trials in patients with relapsed indolent lymphoma. The rate of response to rituximab appeared to be markedly higher in patients with follicular lymphoma than in those with small lymphocytic disease (56 or 60% versus 13 or 15%). 85 to 94% of patients reported adverse events during clinical trials of rituximab; 90% of events were mild or moderate. The most common adverse event, a transient set of flu-like symptoms during the first infusion in approximately 50 to 87% of patients, generally resolved completely in < 3 hours. Diphenhydramine and/or paracetamol was administered to some patients. In 10% of patients, the flu-like symptoms during the first infusion were accompanied by bronchospasm and/or hypotension or severe cytokine release syndrome. Patients were generally able to complete treatment after these symptoms revolved.

Animals↗

PubMed1999

Palivizumab.

The humanised monoclonal antibody palivizumab has been developed for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in infants at high risk; RSV is the most common cause of lower respiratory tract infections in infants. Palivizumab specifically inhibits an epitope at the A antigenic site of the F protein of RSV subtypes A and B. RSV replication was inhibited in nasal and tracheal aspirates from infants receiving palivizumab 15 mg/kg. Mean 30-day trough serum concentrations of palivizumab were consistently about 70 mg/L in infants receiving repeated intramuscular or intravenous palivizumab 15 mg/kg. This is above the target serum concentration of 40 mg/L estimated to reduce pulmonary RSV replication by >99% in animal studies. In a large multicentre trial in 1502 infants at high risk of RSV infection, intramuscular palivizumab 15 mg/kg more than halved the incidence of RSV-attributable hospitalisation to 4.8% compared with 10.6% in placebo recipients. In the same group of high-risk infants, palivizumab significantly decreased total days in hospital attributable to RSV infection, days with increased supplemental oxygen requirement, days with moderate to severe lower respiratory tract infections and the incidence of admissions to intensive care. It had no effect on the incidence or total number of days of ventilation. Palivizumab was well tolerated during clinical trials in infants at risk of RSV infection. The incidence of adverse events was similar in placebo (10%) and palivizumab (11%) groups. Fever, irritability and injection site reaction were the most commonly reported adverse events.

Animals↗

PubMed1999

Topical imiquimod: a review of its use in genital warts.

UNLABELLED: Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-alpha and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of > or = 50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete or partial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of > or = 1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosuppressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in < or = 67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. CONCLUSION: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies. which are administered in the physician's office, imiquimod cream is a self-administered therapy for outpatient use.

Adjuvants, Immunologic↗

PubMed1999

Rofecoxib.

Rofecoxib selectively inhibits cyclo-oxygenase-2 in a dose-dependent manner in humans. No significant inhibition of cyclo-oxygenase-1 is observed with rofecoxib up to doses of 1000 mg. In 4 large double-blind randomised trials performed in patients with osteoarthritis, rofecoxib 12.5 and 25 mg/day significantly improved physical functioning, assessed using the Western Ontario and McMasters Universities Osteoarthritis Index and patient or investigator global assessment, compared with placebo. In addition, rofecoxib showed similar clinical efficacy to that observed with diclofenac 50 mg 3 times daily, ibuprofen 800 mg 3 times daily and nabumetone 1500 mg once daily. Rofecoxib is also an effective analgesic in patients with primary dysmenorrhoea or postoperative dental pain and demonstrates similar analgesic efficacy to that of naproxen sodium and ibuprofen. Rofecoxib is generally well tolerated. The most common adverse events associated with rofecoxib are diarrhoea, headache, nausea and upper respiratory tract infection. There was a significantly lower incidence of upper-gastrointestinal adverse events (perforations, ulcers and bleeds) in patients with osteoarthritis receiving rofecoxib 12.5, 25 or 50 mg/day than in those receiving ibuprofen, diclofenac or nabumetone.

Analgesics↗

PubMed1999

Gatifloxacin.

Gatifloxacin is a novel extended-spectrum fluoroquinolone with improved gram-positive and anaerobe coverage compared with older agents such as ciprofloxacin. It has good activity (but is slightly less active than ciprofloxacin) against Enterobacteriaceae. Gatifloxacin is generally 2- to 4-fold more active than ciprofloxacin against staphylococci, streptococci and enterococci and 4- to 16-fold more active than ciprofloxacin against anaerobes, including Clostridium and Bacteroides spp. In comparative clinical trials that included patients with lower respiratory tract, urinary tract, skin and soft tissue or gonococcal infections, clinical cure rates of > or = 89% were achieved with oral gatifloxacin 400 mg/day for 7 to 14 days. Data from a subset of North American patients included in a multinational trial showed that oral gatifloxacin 400 mg/day produced a significantly higher clinical cure rate than cefuroxime axetil 250 mg twice daily (89 vs 77%; p = 0.01) in patients with acute exacerbations of chronic bronchitis. The clinical efficacy of gatifloxacin was similar to that of clarithromycin or levofloxacin or ceftriaxone (with or without erythromycin) in the treatment of patients with community-acquired pneumonia. Oral gatifloxacin 400 mg/day showed clinical and bacteriological efficacy similar to that of levofloxacin in patients with skin and soft tissue infections. In patients with urinary tract infections, clinical cure and bacterial eradication rates achieved with a single 400 g oral dose of gatifloxacin were similar to those produced with ciprofloxacin. In a pooled analysis of tolerability data from trials that included 3021 patients treated with oral gatifloxacin 400 mg/day, the most commonly reported adverse events were nausea (8%), diarrhoea (4%), headache (4%) and dizziness (3%). The drug was reported to be well tolerated. Gatifloxacin does not appear to cause phototoxic effects.

Anti-Infective Agents↗

PubMed1999

Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections.

UNLABELLED: Quinupristin/dalfopristin is the first parenteral streptogramin antibacterial agent, and is a 30:70 (w/w) ratio of 2 semisynthetic pristinamycin derivatives. The combination has inhibitory activity against a broad range of gram-positive bacteria including methicillin-resistant staphylococci, vancomycin-resistant Enterococcus faecium (VREF), drug-resistant Streptococcus pneumoniae, other streptococci, Clostridium perfringens and Peptostreptococcus spp. The combination also has good activity against selected gram-negative respiratory tract pathogens including Moraxella catarrhalis, Legioniella pneumophila and Mycoplasma pneumoniae. Quinupristin/dalfopristin has poor activity against E. faecalis. The combination is bactericidal against staphylococci and streptococci, although constitutive erythromycin resistance can affect its activity. As for many other agents, quinupristin/dalfopristin is generally bacteriostatic against E. faecium. In patients with methicillin-resistant S. aureus (MRSA) or VREF infections participating in prospective emergency-use trials, quinupristin/dalfopristin 7.5 mg/kg every 8 or 12 hours achieved clinical or bacteriological success in > or =64% of patients. Emergence of resistance to quinupristin/dalfopristin was uncommon (4% of patients) in those with VREF infections. Quinupristin/dalfopristin 7.5 mg/kg 8- or 12-hourly also achieved similar clinical success rates to comparator agents in patients with presumed gram-positive complicated skin and skin structure infections or nosocomial pneumonia (administered in combination with aztreoman) in 3 large multicentre randomised trials. Systemic adverse events associated with quinupristin/dalfopristin include gastrointestinal events (nausea, vomiting and diarrhoea), rash and pruritus. Myalgias and arthralgias also occur at an overall incidence of 1.3%, although higher rates (2.5 to 31%) have been reported in patients with multiple comorbidities. Venous events are common if the drug is administered via a peripheral line; however, several management options (e.g. use of central venous access, increased infusion volume) may help to minimise their occurrence. Hyperbilirubinaemia has been documented in 3.1% of quinupristin/dalfopristin recipients versus 1.3% of recipients of comparator agents. Quinupristin/dalfopristin inhibits cytochrome P450 3A4 and therefore has the potential to increase the plasma concentrations of substrates of this enzyme. CONCLUSIONS: Quinupristin/dalfopristin, the first parenteral streptogramin, offers a unique spectrum of activity against multidrug-resistant gram-positive bacteria. In serious gram-positive infections for which there are other treatment options available, the spectrum of activity and efficacy of quinupristin/ dalfopristin should be weighed against its tolerability and drug interaction profile. However, in VREF or unresponsive MRSA infections, where few proven treatment options exist, quinupristin/dalfopristin should be considered as a treatment of choice for these seriously ill patients.

Anti-Bacterial Agents↗