weeks (n=134) or 300 mg every four weeks (n=139). the results of the trial demonstrated a significant protective effect (p<0.01) against pjp with the 300 mg every four week dosage regimen compared to the 30 mg every two week dosage regimen. the 300 mg dose regimen reduced the risk of developing pjp by 50 to 70% compared to the 30 mg regimen. a total of 293 patients (72% of all patients) also received zidovudine at sometime during the trial. the analysis of the data demonstrated the efficacy of the 300 mg dose even after adjusting for the effect of zidovudine. the results of the trial further demonstrate that the dose and frequency of dosing are important to the efficacy of nebupent prophylaxis in that multiple analyses consistently demonstrated a trend toward greater efficacy with 300 mg every four weeks as compared to 150 mg every two weeks. no dose-response was observed for reduction in overall mortality; however, mortality from pjp was low in all three dosage groups.

used with flow limited by setting the flowmeter at 5 to 7 liters per minute or by setting the pressure at 22 to 25 psi. low pressure (less than 20 psi) compressors should not be used. stability freshly prepared solutions for aerosol use are ­recommended. after reconstitution with sterile water, the nebupent solution is stable for 48 hours in the original vial at room temperature if protected from light.

testinal: abdominal cramps, abdominal pain, constipation, dry mouth, dyspepsia, gastritis, gastric ulcer, gingivitis, hiatal hernia, hypersalivation, oral ulcer/abscess, splenomegaly, and vomiting. hematological: eosinophilia, neutropenia, non-specific cytopenia, pancytopenia, and thrombocytopenia. hepatic: hepatitis, hepatomegaly, and hepatic dysfunction. infection: bacterial pneumonia, central venous line related sepsis, cryptococcal meningitis, cytomegalovirus (cmv) colitis, cmv retinitis, esophageal candida, histoplasmosis, kaposi’s sarcoma, non-specific mycoplasma, oral herpes, non-specific otitis, non-specific pharyngitis, pharyngeal herpes, non-specific serious infection, tonsillitis, tuberculosis, and viral encephalitis. metabolic: hyperglycemia, hypoglycemia, and hypocalcemia. musculoskeletal: arthralgia, gout, and myalgia. neurological: anxiety, confusion, depression, drowsiness, emotional lability, hallucination, hypesthesia, insomnia, memory loss, neuralgia, neuropathy, non-specific neuropathy, nervousness, paranoia, paresthesia, peripheral neuropathy, seizure, tremors, unsteady gait, and vertigo. reproductive: miscarriage. respiratory system: asthma, bronchitis, bronchospasm, chest congestion, chest tightness, coryza, cyanosis, eosinophilic or interstitial pneumonitis, gagging, hemoptysis, hyperventilation, laryngitis, laryngospasm, non-specific lung disorder, nasal congestion, pleuritis, pneumothorax, rales, rhinitis, shortness of breath, non-specific sputum, and tachypnea. skin: desquamation, dry and breaking hair, dry skin, erythema, non-specific dermatitis, pruritus, rash, and urticaria. special senses: blepharitis, blurred vision, conjunctivitis, contact lens discomfort, eye pain or discomfort, hemianopsia, loss of taste, non-specific odor, and smell. urogenital: flank pain, incontinence, nephritis, renal failure, and renal pain. in a clinical trial where some adverse events were solicited by investigators, the incidences were as follows: cough (62.7%) decreased appetite (50.0%) dizziness or light-headedness (45.1%) fatigue (65.7%) fever (51.0%) non-specific serious infection (15.2%) shortness of breath (48.3%) wheezing (32.4%) from post-marketing clinical experience with nebupent the following spontaneous adverse events have been reported: anaphylaxis, colitis, diabetes, dyspnea, esophagitis, hematochezia, increased blood urea nitrogen (bun) and serum creatinine levels, melena, pancreatitis (see warnings ), syndrome of inappropriate antidiuretic hormone (siadh), and torsade de pointes.

and 9.3 ng/ml (range 6.9 to 12.8 ng/ml) in sediment. in the patients who received aerosolized pentamidine, the peak plasma levels of pentamidine were at or below the lower limit of detection of the assay (2.3 ng/ml). following a single 2-hour intravenous infusion of 4 mg/kg of pentamidine isethionate to 6 aids patients, the mean plasma cmax, t 1/2 and clearance were 612 ± 371 ng/ml, 6.4 ± 1.3 hr and 248 ± 91 l/hr respectively. in another study of aerosolized pentamidine in 13 aids patients with acute pjp who received 4 mg/kg/day administered via the ultra vent ® jet nebulizer, peak plasma levels of pentamidine averaged 18.8 ± 11.9 ng/ml after the first dose. during the next 14 days of repeated dosing, the highest observed cmax averaged 20.5 ± 21.2 ng/ml. in a third study, following daily administration of 600 mg of inhaled pentamidine isethionate with the respirgard ® ii nebulizer for 21 days in 11 patients with acute pjp, mean plasma levels measured shortly after the 21st dose averaged 11.8 ± 10.0 ng/ml. plasma concentrations after aerosol administration are substantially lower than those observed after a comparable intravenous dose. the extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known. in rats, intravenous administration of a 5 mg/kg dose resulted in concentrations of pentamidine in the liver and kidney that were 87.5 and 62.3-fold higher, respectively, than levels in those organs following 5 mg/kg administered as an aerosol. no pharmacokinetic data are available following aerosol administration of pentamidine in humans with impaired hepatic or renal function.

9 to 12.8 ng/ml) in sediment. in the patients who received aerosolized pentamidine, the peak plasma levels of pentamidine were at or below the lower limit of detection of the assay (2.3 ng/ml). following a single 2-hour intravenous infusion of 4 mg/kg of pentamidine isethionate to 6 aids patients, the mean plasma cmax, t 1/2 and clearance were 612 ± 371 ng/ml, 6.4 ± 1.3 hr and 248 ± 91 l/hr respectively. in another study of aerosolized pentamidine in 13 aids patients with acute pjp who received 4 mg/kg/day administered via the ultra vent ® jet nebulizer, peak plasma levels of pentamidine averaged 18.8 ± 11.9 ng/ml after the first dose. during the next 14 days of repeated dosing, the highest observed cmax averaged 20.5 ± 21.2 ng/ml. in a third study, following daily administration of 600 mg of inhaled pentamidine isethionate with the respirgard ® ii nebulizer for 21 days in 11 patients with acute pjp, mean plasma levels measured shortly after the 21st dose averaged 11.8 ± 10.0 ng/ml. plasma concentrations after aerosol administration are substantially lower than those observed after a comparable intravenous dose. the extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known. in rats, intravenous administration of a 5 mg/kg dose resulted in concentrations of pentamidine in the liver and kidney that were 87.5 and 62.3-fold higher, respectively, than levels in those organs following 5 mg/kg administered as an aerosol. no pharmacokinetic data are available following aerosol administration of pentamidine in humans with impaired hepatic or renal function.