Incidence Of Serious Adverse Effects Research Articles

Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation – a 12‐week, randomized, double‐blind, placebo‐controlled study

Chronic constipation may result in disabling symptoms, is often unsatisfactorily treated by laxatives and negatively impacts quality of life (QoL). A randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of a selective, high-affinity 5-HT(4) receptor agonist, prucalopride, in patients with chronic constipation [<or=2 spontaneous complete bowel movements (SCBMs)/week]. Placebo, 2 or 4 mg prucalopride was administered orally once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients with >or=3 SCBMs/week, averaged over 12 weeks. Other assessments included BM frequency, constipation-related QoL and symptoms and tolerability. Among 641 patients, significantly more patients taking prucalopride 2 or 4 mg (24%) than placebo (12%), achieved the primary efficacy endpoint (>or=3 SCBMs/week) or an increase of >or=1 SCBMs/week; 43% and 47% vs. 28% respectively. Prucalopride-treated patients also achieved significantly greater satisfaction with treatment and bowel function, and improved perception of constipation severity and constipation-related QoL, compared with placebo. Most frequent treatment-related adverse events were headache, abdominal pain, nausea and diarrhoea (mainly during day 1). There were no differences in comparison to placebo in the incidence of serious adverse effects or cardiovascular events. Over 12 weeks, prucalopride was effective and well tolerated in chronic constipation.

Adverse Effects of Pharmacotherapies for Attention-Deficit Hyperactivity Disorder

Medication for the treatment of attention-deficit hyperactivity disorder (ADHD) is in widespread use globally. There is considerable data suggesting that overall, the adverse effect burden from this use is dose dependent and is in the mild to moderate category, but few comprehensive reviews exist of the epidemiology of adverse effects alone. This review provides a general and systems-specific summary of the scientific literature regarding adverse effect data for the drugs in general use for the treatment of ADHD. Although several areas lack definitive data, current evidence suggests that, for the majority of those treated for ADHD, the medications currently available pose little in the way of risk of significant harm. Epidemiological data suggest a low incidence of serious adverse effects, whilst the less serious adverse effects, such as insomnia and anorexia, are relatively common. Also, some specific areas of study suggest lower risks of harm than previously thought, e.g. tic disorders and seizures. However, pre-existing conditions and other interindividual differences may raise the risk of harmful adverse effects, which adds emphasis to the need for careful pretreatment assessment and monitoring. Potential but unlikely long-term treatment effects need to be investigated as carefully as possible, particularly with regard to cardiac sequelae and carcinogenesis. There are both overlaps and differences between the adverse effects of stimulants and nonstimulants, such as atomoxetine. For example, the latter shares the stimulant group's potential for changing cardiovascular parameters, but may not cause insomnia.

Comparison of gene expression changes induced by biguanides in db/db mice liver

Large-scale clinical studies have shown that the biguanide drug metformin, widely used for type 2 diabetes, to be very safe. By contrast, another biguanide, phenformin, has been withdrawn from major markets because of a high incidence of serious adverse effects. The difference in mode of action between the two biguanides remains unclear. To gain insight into the different modes of action of the two drugs, we performed global gene expression profiling using the livers of obese diabetic db/db mice after a single administration of phenformin or metformin at levels sufficient to cause a significant reduction in blood glucose level. Metformin induced modest expression changes, including G6pc in the liver as previously reported. By contrast, phenformin caused changes in expression level of many additional genes. We used a knowledge-based bioinformatic analysis to study the effects of phenformin. Differentially expressed genes identified in this study constitute a large gene network, which may be related to cell death, inflammation or wound response. Our results suggest that the two biguanides show a similar hypoglycemic effect in db/db mice, but phenformin induces a greater stress on the liver even a short time after a single administration. These findings provide a novel insight into the cause of the relatively high occurrence of serious adverse effect after phenformin treatment.

Use of Second-Generation Antiepileptic Drugs in the Pediatric Population

Epilepsy is common in the pediatric population. Nine second-generation antiepileptic drugs have been approved in the US for use in epilepsy over the past 15 years: felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, zonisamide, and pregabalin. Their use in pediatric patients is fairly widespread, despite most of these agents not having US FDA indications for use. Felbamate and gabapentin were the first two second-generation antiepileptic drugs to be approved in the US. Felbamate use has been limited because of the occurrence of hepatotoxicity and aplastic anemia. Although gabapentin is a fairly well tolerated antiepileptic drug, its use has also been limited as a result of inconsistent efficacy and concern about seizure exacerbation. Lamotrigine and topiramate are broad-spectrum antiepileptic drugs with efficacy in a wide variety of seizure types. Both agents have some tolerability concerns: rash with lamotrigine and neuropsychiatric events with topiramate. There are very little data on tiagabine use in children, but this agent appears to be effective and to have a good tolerability profile. Levetiracetam is a second-generation antiepileptic agent that is available intravenously. Considering its good efficacy, fast onset of action, and low incidence of serious adverse effects, its use in the acute setting could potentially increase. Oxcarbazepine and zonisamide have been relatively well studied in pediatric seizure patients, including use as monotherapy. Both agents have demonstrated good efficacy and tolerability for patients as young as 1 month old. Vigabatrin and rufinamide are currently not available in the US, but have been shown to have some success in other countries. Pregabalin is the newest antiepileptic agent, but lacks pediatric data currently.

Adverse effects of spinal manipulation

If one is to draw any conclusions from the recent article by Ernst (JRSM 2007;100:330-338),1 two assumptions must be made: That Ernst's reviews are not without their limitations; That correlation and causal effect are the same thing with respect to serious adverse effects. Having done this, we learn that spinal manipulation may or may not help and that the incidence of serious adverse effects is unknown because not enough have been reported. This is clearly a case for more research to be done to define the extent to which under-reporting, bias and even conspiracy theories contribute to their real incidence—but to continue to ignore evidence of the effectiveness of spinal manipulation, as outlined in previous letters to the Journal (JRSM 2006;99:277-278),2-4 in order to repeat the mantra that ‘it doesn't work and it'll probably harm you’ is bad science that does no-one any good. Might I suggest that a way ahead, in the UK at least, is for Ernst and/or the JRSM to speak to regulatory bodies such as the General Chiropractic Council4 or the General Osteopathic Council5 before publication? This is an efficient way to learn about current research in the professions, to realize that that systems are in place for adverse event reporting and to recognize that some popular generalizations about the activities of chiropractors and osteopaths are inaccurate. Lighting the touch-paper of ‘an eclectic and combustible mix’, to quote the Editor (JRSM 2007;100:299), may attract attention to the Journal, but one wonders at what price?

Adverse effects of spinal manipulation

If one is to draw any conclusions from the recent article by Ernst (JRSM 2007;100:330-338),1 two assumptions must be made: That Ernst's reviews are not without their limitations; That correlation and causal effect are the same thing with respect to serious adverse effects. Having done this, we learn that spinal manipulation may or may not help and that the incidence of serious adverse effects is unknown because not enough have been reported. This is clearly a case for more research to be done to define the extent to which under-reporting, bias and even conspiracy theories contribute to their real incidence—but to continue to ignore evidence of the effectiveness of spinal manipulation, as outlined in previous letters to the Journal (JRSM 2006;99:277-278),2-4 in order to repeat the mantra that ‘it doesn't work and it'll probably harm you’ is bad science that does no-one any good. Might I suggest that a way ahead, in the UK at least, is for Ernst and/or the JRSM to speak to regulatory bodies such as the General Chiropractic Council4 or the General Osteopathic Council5 before publication? This is an efficient way to learn about current research in the professions, to realize that that systems are in place for adverse event reporting and to recognize that some popular generalizations about the activities of chiropractors and osteopaths are inaccurate. Lighting the touch-paper of ‘an eclectic and combustible mix’, to quote the Editor (JRSM 2007;100:299), may attract attention to the Journal, but one wonders at what price?

Pharmacokinetics and Tolerability of a Higher Rifampin Dose versus the Standard Dose in Pulmonary Tuberculosis Patients

Rifampin is a key drug for tuberculosis (TB) treatment. The available data suggest that the currently applied 10-mg/kg of body weight dose of rifampin may be too low and that increasing the dose may shorten the treatment duration. A double-blind randomized phase II clinical trial was performed to investigate the effect of a higher dose of rifampin in terms of pharmacokinetics and tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of daily TB treatment. Tolerability was assessed during the 6-month treatment period. The geometric means of exposure to rifampin (area under the concentration-time curve from 0 to 24 h [AUC(0-24)]) were increased by 65% (P < 0.001) in the higher-dose group (79.7 mg.h/liter) compared to the standard-dose group (48.5 mg.h/liter). Maximum rifampin concentrations (C(max)) were 15.6 mg/liter versus 10.5 mg/liter (49% increase; P < 0.001). The percentage of patients for whom the rifampin C(max) was > or =8 mg/liter was 96% versus 79% (P = 0.094). The pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus 20%; P = 0.054), but no patient developed severe hepatotoxicity. Increasing the rifampin dose was associated with a more than dose-proportional increase in the mean AUC(0-24) and C(max) of rifampin without affecting the incidence of serious adverse effects. Follow-up studies are warranted to assess whether high-dose rifampin may enable shortening of TB treatment.

Long‐term results with azathioprine therapy in patients with corticosteroid‐dependent Crohn’s disease: Open‐label prospective study

A substantial number of patients with Crohn's disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open-label study evaluated the long-term safety and efficacy of AZA in steroid-dependent CD patients. Adult patients with steroid-dependent CD were enrolled for AZA therapy over a 7-year period. The average dose of AZA was 2.0-3.0 mg/kg per day, adjusted according to clinical response and occurrence of adverse effects. Steroid therapy was tapered off according to a predefined schedule. Long-term outcome and adverse reactions were evaluated. Sixty-nine patients were prospectively included. Steroid-free remission was achieved in 68-81% of patients, partial response in 14.5-27.3% and failure to respond to AZA in 4-15.9% over the initial 48 months. However, the rate of wean from steroid therapy decreased to 53-60% while the rate of failure increased from 6.7% to 17.6% after this period. A breakthrough of symptoms during continuous AZA therapy was common, particularly after 48 months on AZA. The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non-responders (5197 +/- 1250 cells/mm(3) vs 8340 +/- 1310 cells/mm(3), respectively; P < 0.01). Azathioprine was relatively well-tolerated and the incidence of serious adverse effects was small. Azathioprine was relatively safe and moderately effective for long-term maintenance of steroid-free clinical remission in corticosteroid-dependent CD patients. Patients were more successfully weaned from prednisone treatment, and clinical remission was more often maintained during the first 48 months of AZA therapy. A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence.

Surveillance of adverse effects during a vaccination campaign against meningitis C

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Prioritizing health‐care funding

In the face of limited resources, on what basis should we prioritize health-care funding? The most influential consideration should be the knowledge that an intervention does something beneficial for the person who receives it. Rather than using imposed knowledge or knowledge obtained by grace, modern medicine uses knowledge obtained by rational thought. Traditionally, two philosophical schools of rational thought support medical interventions: empiricism and rationalism. Empiricist knowledge underpins the treatment of risk, while rationalist knowledge underpins the treatment of disease. To introduce reasoned order into the rationing process we must understand the limitations inherent in the application of these two forms of knowledge. Why are screening programmes for breast and uterine cervical cancer supported while severe restrictions are placed on treatments for chronic arthritis? Can the benefits of cholesterol-lowering drugs be measured? Empiricism has achieved an unchallenged ascendancy in modern health-care delivery. Is this ascendancy justified? There is a need for reference criteria to compare the benefits of competing interventions across disciplines. As a starting point for debate we propose that interventions should be given a priority based on how closely they fulfil five criteria: knowledge of disease pathophysiology, measurability of short-term and long-term benefits, incidence of serious adverse effects and affordability. It is only by using and refining such funding criteria that better public understanding of the rationing process will be achieved and political interference minimized.

A benefit-risk assessment of agents used in the secondary prevention of stroke.

Stroke is a major cause of morbidity and mortality. Full assessment of stroke or transient ischaemic attack (TIA) patients is required to identify all risk factors and apply appropriate secondary preventative strategies. Antiplatelet therapies are effective in the secondary prevention of ischaemic stroke and can be justified despite adverse effects such as gastrointestinal haemorrhage. Aspirin (acetylsalicylic acid), aspirin plus dipyridamole, ticlopidine and clopidogrel are all of value but their adverse effect profiles vary significantly. Combinations of antiplatelet agents may offer additional benefit but not all combinations have been studied in stroke patients. Anticoagulation with agents such as warfarin is effective with coexisting atrial fibrillation and other conditions predisposing to cardioembolic stroke. Antihypertensive agents have been extensively studied in the primary prevention of stroke; however, relatively few trials of antihypertensive agents in the secondary prevention of stroke are available. The incidence of adverse effects of antihypertensive agents is relatively low and the benefit-risk profile would tend to favour their use in the secondary prevention of stroke. Recent studies of ACE inhibitors have identified an important role for these agents in the secondary prevention of stroke even in those who are normotensive and in those who have had a haemorrhagic stroke. The incidence of serious adverse effects with ACE inhibitors appears relatively low. Lipid-lowering agents may have a role to play in certain groups of patients with stroke. The incidence of adverse effects is relatively low with HMG-CoA reductase inhibitors. Cigarette smoking is an important risk factor for stroke and evidence is available that smoking cessation does reduce the individual's risk of stroke. Pharmacological agents are available to help smoking cessation. In patients with diabetes mellitus, intensive regimens with insulin and oral hypoglycaemic agents have so far not definitively been shown to reduce the incidence of macrovascular complications such as stroke. Tight glycaemic control has been shown to improve microvascular complications such as retinopathy, nephropathy and neuropathy and hence this is reason enough to advocate the use of these agents. Future developments in the treatment of diabetes may help. Secondary prevention of stroke has improved greatly over the past decade and hopefully will continue to improve. The use of pharmacological agents available currently and in the future will be clarified and refined as further clinical trials report.

Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder

ABSTRACTNefazodone, an antidepressant agent with a phenylpiperazine structure, has a pharmacological profile that is distinct from other antidepressant drugs. Like many other antidepressants, nefazodone inhibits the reuptake of norepinephrine and serotonin from the synaptic cleft. Unlike other antidepressants, nefazodone is also a potent antagonist of 5‐HT2 serotonergic receptors. In addition, nefazodone is a weak antagonist of α1‐adrenergic receptors, but has little or no affinity for cholinergic, histaminergic, or dopaminergic receptors. In placebo‐controlled clinical trials, nefazodone has been found to be an effective antidepressant drug with minimal cardiovascular action and significantly fewer side effects than imipramine. Since nefazodone is an effective antidepressant with a low incidence of serious adverse effects, it may be particularly useful in major depressive disorder patients who are intolerant of the anticholinergic or serotonergic side effects of other antidepressants, or who do not respond to treatment with other antidepressant agents. In this paper, we review the mechanisms of action, the pharmacokinetics, and the antidepressant efficacy of nefazodone.

ORAL IRON CHELATION WITH DEFERIPRONE

Deferiprone is the most widely studied oral iron chelator and, at present, the only one shown to be effective in achieving negative iron balance in long-term clinical trials for chronic iron overload. Because of its adverse effects (e.g., agranulocytosis and arthropathy) its use is presently restricted to clinical trials and to countries where desferrioxamine is unavailable. Deferiprone was licensed for clinical use in India in 1995. Clinical trials are in progress in many centers worldwide that will provide further information on the long-term effectiveness of deferiprone as well as on the incidence of serious adverse effects in patients with iron overload. Trials of combined use of deferiprone and desferrioxamine are also in progress. In the meantime, deferiprone is an acceptable alternative for patients who cannot use desferrioxamine because of serious adverse effects, lack of compliance, or unavailability. Elucidation of the mechanisms involved in the agranulocytosis and arthropathy associated with deferiprone is still needed, as are methods to predict individual susceptibility to these adverse effects and ways of preventing them. In addition, new indications for iron-chelating therapy are continuously being explored.

Adverse Effects of Drugs Used in the Management of Opportunistic Infections Associated with HIV Infection

Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses. First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population. Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options. Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents. The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis. Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile. There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet. Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity. The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis. Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

Preference for shorter acting sulfa drugs may reduce the incidence of serious adverse effects

Preference for shorter acting sulfa drugs may reduce the incidence of serious adverse effects

Moricizine: A Novel Antiarrhythmic Agent

Moricizine is a phenothiazine derivative with Vaughan Williams class 1 antiarrhythmic properties. It undergoes extensive first-pass metabolism, has a bioavailability of 34-38 percent, and is 95 percent bound to plasma proteins. Moricizine is extensively metabolized and may have pharmacologically active metabolites. A recent clinical study has shown that moricizine is slightly less effective than encainide or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moricizine was equally or more effective in suppressing ventricular premature depolarizations, couplets, and nonsustained ventricular tachycardia. Further studies are needed comparing moricizine with other class 1 agents in the treatment of life-threatening arrhythmias; available data suggest that moricizine is comparable with these agents in the treatment of ventricular tachycardias and fibrillation. Moricizine appears to have a low incidence of serious adverse effects compared with other antiarrhythmics. This combination of apparently similar efficacy with a decreased incidence of adverse effects makes moricizine a worthwhile addition to currently available antiarrhythmic agents.

Comparison of intramuscular glucagon and intravenous dextrose in the treatment of hypoglycaemic coma in an accident and emergency department.

Hypoglycaemia remains a serious and much feared complication of insulin therapy. In this study, patients attending an accident and emergency department in hypoglycaemic coma were randomized to treatment with either intravenous dextrose (25g) or intramuscular glucagon (1mg), administered into the right thigh. Restoration of normal conscious level was slower after glucagon than dextrose (9.0 vs 3.0 min, P less than 0.01), although the average duration of hypoglycaemic coma was 120 min. Two patients in the glucagon-treated group, who failed to show satisfactory recovery after 15 min, required additional treatment with intravenous dextrose. On questioning following recovery, all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and, although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department, this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects.

Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis.

Epoetin (recombinant human erythropoietin) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The therapeutic efficacy of epoetin in the treatment of anaemia associated with chronic renal failure has been established, with almost all patients responding with increases in haematocrit and haemoglobin levels, and improvements in quality of life. Some patients demonstrate relative epoetin resistance and require a higher dosage to achieve target haemoglobin and haematocrit levels. Maintenance of an adequate iron supply is essential and iron supplementation is recommended if serum ferritin is below 100 to 150 micrograms/L or transferrin saturation is less than 20%. The incidence of serious adverse effects may be reduced by maintaining a moderate rate of increase in the haematocrit with close monitoring of blood pressure and dialysis efficacy. Individual titration of epoetin dosage is recommended, with increases made in small increments to achieve haematocrit and haemoglobin levels of 30 to 33% and 10 to 12 g/dl, respectively, although the optimal haematocrit for each patient should be individually determined. Some patients will also require a modest increase in heparin dosage because of a possible increase in clotting tendency. Hypertension is the most common adverse effect in patients with chronic renal failure, occurring partially as a result of increasing blood viscosity and peripheral vascular resistance with the correction of anaemia. Maintenance epoetin therapy has been given for more than 2 years without a decrease in responsiveness and does not appear to adversely affect the outcome of renal transplantation. Thus, epoetin represents a significant therapeutic advance in the treatment of anaemia associated with chronic renal failure and should be considered a first option for these patients. Its potential value in the treatment of anaemia associated with other disorders and in facilitating autologous blood donation remains to be fully determined.

Hydroxyurea in the management of therapy resistant psoriasis.

Eighty-five patients with extensive chronic plaque psoriasis, unresponsive to conventional topical therapy, were treated with long-term hydroxyurea in a dose of 0.5-1.5 g daily. Fifty-two (61%) had a satisfactory remission during treatment without significant adverse effects. Treatment was discontinued in 33 patients (39%), due to an inadequate response or significant relapse during treatment and because of adverse reactions (19%). Four (4.7%) patients on hydroxyurea developed actinic psoriasis. Significant haematological abnormalities occurred in 30 patients (35%), but these became normal following a reduction in the dose of hydroxyurea or temporarily stopping the drug. In only six was it considered necessary to discontinue treatment because of bone marrow suppression. Our experience suggests that hydroxyurea is an effective long-term treatment for psoriasis that is refractory to conventional topical therapy and that the incidence of serious adverse effects compares favourably with other cytotoxic drugs.

Aerosolized pentamidine in HIV. Promising new treatment for Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is the most common life-threatening disease diagnosed in patients infected with the human immunodeficiency virus (HIV). Patients treated for their initial episode are at risk for recurrence of the disease. HIV-positive patients with low T4 lymphocyte counts are also at risk. Conventional treatment regimens with parenteral pentamidine isethionate (Pentam 300) or trimethoprim-sulfamethoxazole have a 50% to 60% incidence of serious adverse effects and a 20% to 40% rate of failure. Aerosolized pentamidine represents a promising new therapy for HIV-infected patients. Major adverse reactions have not been reported with its use. The Food and Drug Administration's (FDA's) recent approval of aerosolized pentamidine may also have a positive effect on healthcare costs by preventing episodes of P carinii pneumonia. In addition, FDA approval may result in reimbursement of patients for this new therapy by more insurance companies.