Biomedical subjects

H M Lamb

Publications and source records attributed to H M Lamb.

36 records · Page 2Linked to original sources

PubMed1999

Diclofenac/misoprostol. Pharmacoeconomic implications of therapy.

The combined formulation of diclofenac/misoprostol provides effective relief of pain and inflammation, with a 2- to 3-fold lower incidence of NSAID-associated gastroduodenal ulcers than diclofenac monotherapy. Both components of the combined formulation have been widely used and have well documented efficacy and tolerability profiles. Compared with other agents used as prophylaxis for NSAID-induced gastropathies, misoprostol is generally considered to have the most extensive outcomes data establishing its efficacy in preventing both gastric and duodenal ulcers associated with long term NSAID use. Economic analyses conducted to date have shown that diclofenac/misoprostol is associated with similar or lower total direct medical treatment costs compared with other NSAIDs (with or without coprescribed misoprostol or an alternate prophylactic agent). As with pharmacoeconomic studies of coprescribed misoprostol with NSAIDs, the most favourable results with the combined formulation of diclofenac/misoprostol appear to be in patients at high risk of developing NSAID-associated gastroduodenal ulcers (e.g. the elderly). Although economic analyses with diclofenac/misoprostol were conducted in several different countries using a variety of methodologies and employing a wide range of clinical and economic assumptions, results have been generally favourable for the combined formulation. However, as is the case with pharmacoeconomic analyses in general, results of individual studies with diclofenac/misoprostol may not be generalisable between countries and are subject to change over time. Overall, clinical and economic data suggest that the optimal and most cost-effective use of the combined formulation of diclofenac/misoprostol is in patients requiring long term NSAID therapy who are at increased risk of developing NSAID-induced gastropathy, such as elderly patients with rheumatoid arthritis or osteoarthritis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Capromab pendetide. A review of its use as an imaging agent in prostate cancer.

UNLABELLED: Capromab pendetide, radiolabelled with indium-111, is a radioimmunoscintigraphic imaging agent used in patients with prostate cancer. It consists of a murine monoclonal antibody (7E11-C5.3) covalently jointed to a linker-chelator molecule. 7E11-C5.3 is thought to be directed against the intracellular domain of human prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein expressed by prostate epithelial cells. The diagnostic utility of capromab pendetide has been investigated in 2 distinct patient groups. In patients with untreated prostate cancer at high risk for pelvic lymph node metastases, capromab pendetide imaging had respective sensitivities and specificities of 52 and 96% in 1 study and 62 and 72% in another, as confirmed by pelvic lymph node dissection biopsy results. In patients with suspected occult recurrent or residual disease after prostatectomy, capromab pendetide had respective sensitivities and specificities of 49 and 71% in 1 study and 77 and 35% in another for detection of cancer in the prostate bed. Almost half of these patients also had evidence of lesions outside the prostate fossa (usually in the pelvic and abdominal lymph nodes) according to immunoscintigraphic scans, but too few cases were confirmed to allow an evaluation of capromab pendetide. Four per cent of patients who received single doses of capromab pendetide experienced adverse events. Elevated bilirubin levels, hypertension and hypotension each affected 1% of patients and elevated liver enzymes and injection site reactions < 1% of patients. Detectable human anti-mouse antibodies were reported in 8% of patients after a single dose of capromab pendetide and in 19% of patients after repeat infusions. CONCLUSIONS: Capromab pendetide offers improved sensitivity in the detection of prostate cancer over other noninvasive techniques. When used in conjunction with other techniques, it offers the possibility of defining the extent of localised and metastatic disease, thereby refining patient management.

Antibodies, Monoclonal↗

PubMed1998

Zopiclone. An update of its pharmacology, clinical efficacy and tolerability in the treatment of insomnia.

Zopiclone is a non-benzodiazepine hypnotic which was first reviewed in Drugs in 1986. At that time, zopiclone had shown hypnotic efficacy superior to that of placebo, but had not been extensively compared with benzodiazepine hypnotics in patients with insomnia. A much larger body of clinical data is now available, allowing a more detailed evaluation than was previously possible. Together with results from earlier studies, subsequent clinical trials have shown that zopiclone is generally at least as effective as the benzodiazepines (regardless of duration of action) in the treatment of insomnia, although comparisons between zopiclone and flurazepam have produced inconsistent results. Tolerance to the effects of zopiclone was not seen in short term clinical trials (< or = 4 weeks); data from longer term studies are conflicting and the potential for tolerance during long term zopiclone treatment is therefore unclear. Zopiclone has a relatively low propensity to cause residual clinical effects (such as difficulty in waking or reduced morning concentration). Rebound of insomnia to a level below that at baseline can occur after withdrawal of zopiclone, but, on the basis of data from short term studies, does not appear to be common. Data from prescription-event monitoring suggest that zopiclone does not have a high dependence potential (at least in those who are not regular drug abusers/addicts). Zopiclone is well tolerated in both the elderly and younger patients with insomnia. A bitter aftertaste is usually the most common adverse event, but is relatively infrequent (3.6% in the largest available postmarketing study). Thus, zopiclone is now firmly established as an effective and well tolerated hypnotic agent. Although the available data on rebound insomnia and dependence liability are encouraging, potential differences between zopiclone and the benzodiazepines in these respects may have little clinical relevance in the context of short term intermittent use of hypnotics, as it currently recommended. A low propensity for rebound insomnia and dependence might prove valuable during long term hypnotic therapy (which, although not recommended, is a clinical reality). However, the risk-benefit profile of zopiclone in this context remains unknown. Nevertheless, zopiclone is clearly a suitable alternative to the benzodiazepines for the short term treatment of insomnia.

Azabicyclo Compounds↗

PubMed1998

Levofloxacin. Its use in infections of the respiratory tract, skin, soft tissues and urinary tract.

UNLABELLED: Levofloxacin, the optically pure levorotatory isomer of ofloxacin, is a fluoroquinolone antibacterial agent. Like other fluoroquinolones, it acts on bacterial topoisomerase and has activity against a broad range of Gram-positive and Gram-negative organisms. Levofloxacin also appears to have improved activity against Streptococcus pneumoniae compared with ciprofloxacin or ofloxacin. Levofloxacin distributes well and achieves high levels in excess of plasma concentrations in many tissues (e.g., lung, skin, prostate). High oral bioavailability allows switching from intravenous to oral therapy without dosage adjustment. In patients with mild to severe community-acquired pneumonia receiving treatment for 7 to 14 days, oral levofloxacin was similar in efficacy to amoxicillin/clavulanic acid, and intravenous and/or oral levofloxacin was superior to intravenous ceftriaxone and/or oral cefuroxime axetil. With levofloxacin use, clinical success (clinical cure or improvement) rates were 87 to 96% and bacteriological eradication rates were 87 to 100%. In the 5- to 10-day treatment of acute exacerbations of chronic bronchitis, oral levofloxacin was similar in efficacy to oral cefuroxime axetil or cefaclor. Levofloxacin resulted in clinical success in 78 to 94.6% of patients and bacteriological eradication in 77 to 97%. Oral levofloxacin was also similar in efficacy to amoxicillin/clavulanic acid or oral clarithromycin in patients with acute maxillary sinusitis treated for 7 to 14 days. Equivalence between 7- to 10-day therapy with oral levofloxacin and ciprofloxacin was seen in patients with uncomplicated skin and soft tissue infections. Clinical success was seen in 97.8 and 96.1% of levofloxacin recipients and bacteriological eradication in 97.5 and 93.2%. Complicated urinary tract infections, including pyelonephritis, responded similarly well to oral levofloxacin or ciprofloxacin for 10 days or lomefloxacin for 14 days. Clinical success and bacteriological eradication rates with levofloxacin occurred in 92 to 93.3% and 93.6 to 94.7% of patients. CONCLUSIONS: Levofloxacin can be administered in a once-daily regimen as an alternative to other fluoroquinolones in the treatment of infections of the urinary tract, skin and soft tissues. Its more interesting use is as an alternative to established treatments of respiratory tract infections. S. pneumoniae appears to be more susceptible to levofloxacin than to ciprofloxacin or ofloxacin. Other newer fluoroquinolone agents that also have enhanced in vitro antipneumococcal activity may not share the well established tolerability profile of levofloxacin, which also appears to improve on that of some older fluoroquinolones.

Animals↗

PubMed1998

Rifapentine.

Rifapentine is a rifamycin antibiotic with antimycobacterial activity. Rifapentine is generally more active against Mycobacterium tuberculosis than rifampicin (rifampin), although strains resistant to rifampicin are usually cross-resistant to rifapentine. Sputum culture conversion rates were slightly higher after 6 months of rifapentine- versus rifampicin-based therapy in patients with pulmonary tuberculosis in a Western study; however, relapse rates were higher in rifapentine recipients during follow-up. The excess relapses in the rifapentine group appeared to be related to poor compliance with nonrifamycin antituberculosis drugs during the intensive phase (first 2 months) of therapy. Rifapentine- and rifampicin-containing regimens produced similar sputum culture conversion rates with low rates of relapse in 2 randomised clinical trials in patients with smear-positive tuberculosis in China. In one trial, there was no difference in sputum culture conversion rates in patients treated with rifapentine once weekly or rifampicin twice weekly in combination with isoniazid and ethambutol during the continuation phase of treatment. Hyperuricaemia, which was reported only during the intensive phase, elevated ALT and AST levels and neutropenia were the most common treatment-related adverse events reported in patients receiving rifapentine- or rifampicin-containing regimens for tuberculosis in 1 Western study.

Animals↗

PubMed1998

Mometasone furoate. A review of its intranasal use in allergic rhinitis.

UNLABELLED: Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. CONCLUSIONS: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.

Anti-Allergic Agents↗

PubMed1998

Ofloxacin. A reappraisal of its use in the management of genitourinary tract infections.

UNLABELLED: Ofloxacin is an established fluoroquinolone agent which achieves good concentrations in genitourinary tract tissues and fluids. It has good in vitro activity against most Enterobacteriaceae, Staphylococcus saprophyticus, methicillin-susceptible S. aureus, Neisseria gonorrhoeae, Chlamydia trachomatis and Haemophilus ducreyi, intermediate activity against Ureaplasma urealyticum and most enterococci, but limited or no in vitro activity against enterococci, Serratia marcescens, Pseudomonas aeruginosa and many anaerobes. However, high concentrations achieved in the urine ensure its activity against most urinary tract pathogens. Ofloxacin demonstrates consistent efficacy in a broad range of urinary tract infections, achieving bacteriological response rates in excess of 80% in uncomplicated and 70% in complicated infections. The efficacy of ofloxacin was similar to that of all comparators tested including other fluoroquinolones, cephalosporins and cotrimoxazole (trimethoprim/sulfamethoxazole). Ofloxacin is also effective as a single-dose regimen in the treatment of uncomplicated gonorrhoea, as a 7-day regimen in uncomplicated C. trachomatis infections, and as monotherapy in uncomplicated pelvic inflammatory disease (PID). Again, ofloxacin demonstrated similar efficacy to alternative treatments in each type of infection. The availability of an intravenous formulation and near-complete oral bioavailability allow ofloxacin to be administered as a sequential regimen without loss of activity. The tolerability and drug interaction profile of ofloxacin is consistent with that of other fluoroquinolones. The most commonly reported adverse events with ofloxacin are gastrointestinal, neurological and dermatological. It was associated with a lower incidence of photosensitivity and tendinitis and higher incidence of some neurological events than some other fluoroquinolones. Ofloxacin seems to have a lower propensity to interact with xanthines than other fluoroquinolones. CONCLUSION: ofloxacin has established efficacy in the treatment of a wide variety of urinary tract infections, although, like other fluoroquinolones, it should be used rationally to preserve its activity. Currently, ofloxacin also holds an important place among fluoroquinolones in the treatment of C. trachomatis infections and uncomplicated PID, although its acceptance as monotherapy in PID is likely to depend on clarification of the causative role of anaerobic pathogens in this infection.

Anti-Infective 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↗

PubMed1998

Letrozole. A review of its use in postmenopausal women with advanced breast cancer.

UNLABELLED: Letrozole is an oral reversible nonsteroidal aromatase inhibitor. Clinical tracer studies show that it inhibits peripheral aromatase by over 98% and suppresses blood and urinary estrogen levels by over 95% after 2 weeks of treatment in postmenopausal women. Letrozole also significantly inhibits intratumoral aromatase in vivo. The action of letrozole appears to be selective for aromatase; long term administration did not affect basal levels of 17 alpha-hydroxyprogesterone or aldosterone, although slight decreases in cortisol levels were observed in 2 studies, these did not appear to be clinically significant. In 2 phase IIb/III trials, letrozole 2.5 mg/day achieved objective response rates of 19.5 and 23.6% which were sustained for a median duration of 24 and 33 months, respectively. The median duration of response compared favourably with both comparator agents, aminoglutethimide and megestrol (15 and 18 months, respectively), as did objective response rates (12.4 and 16.4%). Letrozole 2.5 mg/day was associated with an increase in median survival time of 8 and 3 months compared with aminoglutethimide and megestrol, respectively. According to analyses of overall function, letrozole 2.5 mg/day was significantly superior to both comparators with respect to duration of response and aminoglutethimide with respect to survival. Letrozole has a good short term tolerability profile. The adverse events reported most commonly in association with letrozole 2.5 mg/day in the 2 phase IIb/III trials were headache (1.1 and 7%), nausea (6 and 10.3%), fatigue (3.2 and 5%), hot flushes (4.9 and 5%) and peripheral oedema (6%). Events were usually mild to moderate in severity; adverse events necessitated discontinuation of treatment in 3% of letrozole 2.5 mg/day recipients. CONCLUSIONS: Letrozole, in common with vorozole and anastrozole, offers greater selectivity and potency of aromatase inhibition than the prototype aromatase inhibitor, aminoglutethimide, and can be administered once daily. Available clinical data suggest that letrozole achieves a significantly longer duration of response than megestrol and aminoglutethimide and longer overall survival than aminoglutethimide. However, direct comparisons are required to distinguish between the newer aromatase inhibitors. For this reason, letrozole should be recommended as a second-line treatment in postmenopausal women with advanced breast cancer whose disease has progressed on or failed to respond to antiestrogen therapy.

Administration, Oral↗

PubMed1998

Docetaxel. A pharmacoeconomic review of its use in the treatment of metastatic breast cancer.

UNLABELLED: Advanced breast cancer has a poor prognosis (median duration of survival about 2 years); thus, treatment options are largely palliative. Recent studies with the taxoids docetaxel and paclitaxel suggest that these agents are effective second-line therapy in patients with metastatic breast cancer. Objective response rates range from 30 to 57% with docetaxel monotherapy in clinical trials in patients with advanced disease who had failed to respond to previous therapy, and the median time to disease progression ranges from 17 to 20 weeks. Currently available pharmacoeconomic data relating to docetaxel in the treatment of women with metastatic breast cancer include a cost-minimisation study and 3 cost-utility studies which relate to the UK, French and US healthcare systems. All analyses compared docetaxel with paclitaxel. Since no direct clinical comparisons of these 2 agents have been performed, model assumptions were based on available, rather than comparative, clinical data. The French model also considered vinorelbine monotherapy as a comparator. Considering direct costs only, costs associated with docetaxel ranged from < 0.3% less to 13% more than those of paclitaxel. When utilities were evaluated, docetaxel was associated with incremental gains versus paclitaxel of 33 and 75 additional days of quality-adjusted health in the UK and US studies, respectively, and 22 additional days of quality-adjusted progression-free survival (QPFS) in the French analysis. Thus, the incremental cost utility of docetaxel versus paclitaxel was an estimated Pounds 2431 per quality-adjusted life-year (QALY) in the UK analysis (1994 values) and US$8615 per QALY in the US analysis (1997 values). The French model found that docetaxel cost 700 French francs less for the extra days of QPFS (1993 costs). CONCLUSIONS: Cost-utility analyses, compiled in the absence of direct comparative data, show that docetaxel offers utility gains versus paclitaxel in the treatment of metastatic breast cancer. The incremental cost for these gains is within the accepted range for healthcare interventions.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer.

Idarubicin is an anthracycline agent available as both oral and intravenous formulations. The oral formulation has demonstrated efficacy in the treatment of advanced breast cancer, low-grade non-Hodgkin's lymphoma, myelodysplastic syndromes and as first-line induction therapy of acute myelogenous leukaemia where intravenous anthracycline treatment is precluded. It also has potential in ameliorating blast crisis of chronic myelogenous leukaemia and in multiple myeloma. The most frequent adverse effects associated with oral idarubicin are those commonly found with anthracyclines, namely myelosuppression, nausea and vomiting, diarrhoea and mucositis. There appears to be minimal significant cardiotoxicity with oral idarubicia. In summary; available data concerning oral idarubicin in haematological malignancies and advanced breast cancer are sufficiently encouraging to warrant further research. To maximise the use of oral idarubicin, future studies should define the optimal dose for elderly patients, its comparative efficacy with other available regimens and address quality-of-life and pharmacoeconomic issues associated with the substitution of oral for intravenous chemotherapy.

Antibiotics, Antineoplastic↗

PubMed1997

Samarium 153Sm lexidronam.

Samarium 153Sm lexidronam is a medium energy beta-emitting radioisotope chelated to the tetraphosphate, ethylenediaminetetramethylenephosphonic acid (EDTMP). 153Sm has a physical half-life of 1.9 days. Samarium 153Sm lexidronam concentrates in bone tissue and has a metastatic lesion: normal bone ratio of 4. Clearance of nonskeletal radioactivity after administration of samarium 153Sm lexidronam is rapid, and is almost complete from the blood and urine within 1 and 6 hours, respectively. Some degree of pain relief was achieved in 72% of patients with bone metastases after a single dose of samarium 153Sm lexidronam 1 mCi/kg (37 MBq/kg) compared with 44% of placebo recipients (p < 0.025). Relief was generally attained within 2 weeks and lasted for a median of 8 to 15 weeks. After recurrence of pain, a second dose of samarium 153Sm lexidronam may produce further pain relief in some patients. The dose-limiting toxicity of samarium 153Sm lexidronam is reversible myelosuppression.

Analgesics, Non-Narcotic↗

PubMed1997

Metrifonate.

Explore the source record for details and available documents.

Administration, Oral↗

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

Trovafloxacin.

Trovafloxacin is a fluoroquinolone antibacterial agent with a broad spectrum of activity. Trovafloxacin has similar or 2-fold lower activity than ciprofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa. Against Haemophilus influenzae and Moraxella catarrhalis, trovafloxacin has similar activity to ciprofloxacin. Other susceptible Gram-negative pathogens include Neisseria gonorrhoeae, Chlamydia trachomatis and mycoplasmas. The drug is active against Gram-positive bacteria and consistently displayed greater activity (2- to 8-fold) than ciprofloxacin against all staphylococci and streptococci tested; activity included methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Trovafloxacin has some activity against vancomycin-resistant enterococci. Anaerobes such as Bacteroides and Clostridium spp. are also susceptible to trovafloxacin. Preliminary clinical data suggest that trovafloxacin is effective in the treatment of patients with upper and lower respiratory tract and uncomplicated urinary tract infections and infections caused by C. trachomatis or N. gonorrhoeae. The most frequently noted adverse event with trovafloxacin is dizziness which is reported in 11% of patients versus 3% of those receiving comparator agents. Other commonly reported events (> 1% of patients) are nausea, headache, vomiting, vaginitis and diarrhoea.

Animals↗

PubMed1997

Sumatriptan. A pharmacoeconomic review of its use in migraine.

Migraine is a common illness characterised by severe, often throbbing and/or unilateral headache, which may be accompanied by sensitivity to light or noise. A minority of migraine attacks are preceded by transient visual or sensory disturbances. Migraine is associated with reductions in health-related quality of life both during and between attacks. Despite methodological limitations in cost-of-illness studies, it is clear that the cost of migraine to society is substantial. Indirect costs (primarily workplace productivity losses) make up 75 to 90% of total costs. Direct costs, such as the cost of drug treatment, physician consultation, hospitalisation and emergency room treatment, make up most of the remainder. Sumatriptan is an effective and well tolerated agent in the treatment of migraine. Its main advantage over other agents used in the acute management of migraine appears to be its rapid onset of action. Sumatriptan reduces headache severity within 2 hours of oral administration in 50 to 67% of patients and within 1 hour of subcutaneous administration in 70 to 80% of patients. Headache recurs in approximately 40% of patients who initially respond to oral or subcutaneous sumatriptan; however, a second dose of the drug is effective against the symptoms of recurrence in a majority of patients. Some patients experience relief of non-headache migraine symptoms, including nausea, vomiting, photophobia and phonophobia. Adverse events reported after sumatriptan are generally mild and transient. Data from studies of patients who used their usual therapies and sumatriptan in nonblinded, sequential phases indicate that both workplace and nonworkplace productivity losses were reduced during sumatriptan therapy. A cost-benefit analysis applied to some of these workplace productivity data indicated that, including direct costs and productivity savings, sumatriptan was associated with a net reduction in total cost of migraine. In retrospective cost analyses, sumatriptan was associated with increased prescription costs: the effect of the drug on other direct treatment costs was less clear. A retrospective pharmacoeconomic model suggested that the cost-effectiveness of subcutaneous sumatriptan versus subcutaneous dihydroergotamine depended on which outcome measure was of greatest interest. For measures of rapid relief of migraine, sumatriptan was superior, but the cost of achieving rapid relief was substantial. Sumatriptan improved global quality-of-life scores compared with patients' usual therapy in a randomised crossover trial and appeared to do the same when the drugs were administered in nonblinded, sequential phases in trials which used general and migraine-specific quality-of-life instruments. Thus, sumatriptan is associated with a fast onset of action and improvements in health-related quality of life in patients with migraine. However, the cost of achieving rapid relief of migraine symptoms may be substantial. Compared with patients' usual treatments, sumatriptan appeared to reduce workplace and non-workplace productivity losses. However, few economic data from well controlled prospective comparisons of sumatriptan with other available agents are available to quantify the effect of sumatriptan on the overall cost of migraine.

Economics, Pharmaceutical↗

PubMed1997

Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women.

In women, Chlamydia trachomatis infection often occurs in the urethra or cervix, with up to 70% of infections associated with few or no symptoms. Inadequate treatment may lead to infection of the upper genital tract and subsequent pelvic inflammatory disease (PID) in 10 to 40% of patients. PID causes an increased relative risk of ectopic pregnancy of 2.5 to 7.9 and PID may also lead to tubal infertility in about 17% of patients. 60% of infants born of mothers with C. trachomatis infection may become infected, leading to conjunctivitis in 23% and pneumonia in 21%. All of these sequelae of C. trachomatis infection may require in- or outpatient treatment. With > 4 million infections estimated to occur each year in the US, C. trachomatis is one of the most common and costly of the sexually transmitted pathogens. Treatment options for uncomplicated C. trachomatis infections in nonpregnant women include single-dose azithromycin 1000 mg or doxycycline 100 mg twice daily for 7 days orally. In clinical trials, the bacteriological cure rate of single dose azithromycin 1000 mg (95 to 100%) was similar to that of oral doxycycline 200 mg/day for 7 days (88 to 100%) in nonpregnant women. Azithromycin was at least as well tolerated as doxycycline and was associated with mainly mild gastrointestinal adverse effects including diarrhoea, nausea and abdominal pain. Pharmacoeconomic analyses have sought to determine if the 2.7- to 12-fold higher acquisition costs of azithromycin in comparison with doxycycline are offset by its simple single-dose regimen which is likely to aid patient compliance and so optimise drug efficacy. All analyses were retrospective cost-effectiveness decision-tree models and mainly considered direct costs. All models incorporated an estimate of noncompliance with doxycycline and its influence on efficacy. For the treatment of confirmed C. trachomatis infection, azithromycin saved around $US1200 per major outcome avoided (1993 values; third-party payer perspective in the US) or US$3502 per case of PID avoided (1993 values; US healthcare system perspective) compared with doxycycline. If infection was treated empirically, azithromycin was more costly than doxycycline by $US792 (1993 values), but the result was sensitive to changes of some parameters of the model. Azithromycin was more costly than doxycycline from the perspective of a public health clinic which paid for the treatment of initial infection and acute sequelae only. Thus, pharmacoeconomic data from the US support the use of azithromycin in the treatment of nonpregnant women with confirmed C. trachomatis urogenital infections from the perspective of the healthcare system or third-party payer; however, from the perspective of a public clinic, doxycycline is the less costly option. Decreases in doxycycline compliance or azithromycin acquisition cost are factors that favour azithromycin.

Anti-Bacterial Agents↗

PubMedDate not supplied

Denileukin diftitox.

Denileukin diftitox is a novel interleukin-2 receptor (IL-2R)-targeted diphtheria toxin. It binds to cells expressing IL-2R and inhibits protein synthesis through internalization of the diphtheria toxin fragment. In patients with IL-2R-positive cutaneous T cell lymphoma (CTCL), the overall response rate was 23 and 36%, respectively, after denileukin diftitox 9 or 18 micrograms/kg/day for 5 days every 3 weeks and was 37% in a dose-ranging trial. Quality of life (QOL) improved significantly in patients with CTCL who responded to treatment with denileukin diftitox 9 or 18 micrograms/kg/day compared with QOL at baseline and in nonresponders. In a murine model of IL-2R-expressing malignancy, denileukin diftitox prolonged survival compared with controls. The most common adverse events reported in patients who received denileukin diftitox were hypoalbuminemia, fever/chills, acute hypersensitivity reactions, nausea/vomiting and asthenia. Vascular leak syndrome has occurred during denileukin diftitox therapy. Antibody titers to denileukin diftitox occur in most patients after treatment but the presence of antibodies does not preclude a clinical response.

Animals↗