positioned and closely observed throughout the period of pentamidine isethionate administration. if extravasation occurs, the injection should be discontinued immediately and restarted in another vein. because there are no known local treatment measures which have proven to be useful, management of the extravasation should be symptomatic.

n 50 to 250 ml of 5% dextrose injection, usp. the diluted iv solutions containing pentamidine isethionate should be infused over a period of 60 minutes. aseptic technique should be employed in preparation of all solutions. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. stability after reconstitution with sterile water, the pentamidine isethionate solution is stable for 48 hours in the original vial at room temperature if protected from light. to avoid crystallization, store at 22° to 30°c (72° to 86°f). intravenous infusion solutions of pentamidine isethionate at 1 mg/ml and 2.5 mg/ml prepared in 5% dextrose injection, usp are stable at room temperature for up to 24 hours. intravenous (iv) solutions of pentamidine isethionate have been shown to be incompatible with fluconazole and foscarnet sodium. iv solutions of pentamidine isethionate have been shown to be compatible with iv solutions of zidovudine (azt) and diltiazem hydrochloride.

, or induration at the site of im injection 11.1% rash 3.3% special senses: bad taste 1.7% urogenital: azotemia 8.5% elevated serum creatinine 23.6% elevated blood urea nitrogen 6.6% impaired renal function 28.8% adverse events with a frequency of less than 1% incidence were as follows (no causal relationship to treatment has been established for these adverse events): body as a whole: allergic reaction (i.e. urticaria, itching, rash), anaphylaxis, arthralgia, chills, extrapulmonary pneumocystosis, headache, night sweats, and stevens-johnson syndrome. cardiovascular: abnormal st segment of electrocardiogram, cardiac arrhythmias, cerebrovascular accident, hypertension, palpitations, phlebitis, syncope, tachycardia, vasodilatation, vasculitis and ventricular tachycardia. gastrointestinal: abdominal pain, diarrhea, dry mouth, dyspepsia, hematochezia, hypersalivation, melena, pancreatitis, splenomegaly, and vomiting. hematological: defibrination, eosinophilia, neutropenia, pancytopenia, and prolonged clotting time. hepatic: hepatic dysfunction, hepatitis and hepatomegaly metabolic: hyperglycemia, hyperkalemia, hypocalcemia, and hypomagnesemia. neurological: anxiety, confusion, depression, dizziness, drowsiness, emotional lability, hypesthesia, insomnia, memory loss, neuropathy, nervousness, neuralgia, paranoia, paresthesia, peripheral neuropathy, seizure, tremors, unsteady gait, and vertigo. 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, and tachypnea. skin: desquamation, dry and breaking hair, dry skin, erythema, dermatitis, pruritus, rash, and urticaria. special senses: blepharitis, blurred vision, conjunctivitis, contact lens discomfort, eye pain or discomfort, loss of hearing, loss of taste, and loss of smell. urogenital: flank pain, hematuria, incontinence, nephritis, renal dysfunction and renal failure. from post-marketing clinical experience with pentamidine isethionate, the following adverse events have been reported: cough, diabetes mellitus/ketoacidosis, dyspnea, infiltration (extravasation–see warnings ), and torsades de pointes.

ntrations were between 300 to 500 ng/ml. the concentrations did not appreciably change with time after injection or from day to day. higher plasma concentrations were encountered in patients with an elevated blood urea nitrogen. the patients continued to excrete decreasing amounts of pentamidine in urine up to 6 to 8 weeks after cessation of the treatment. following multiple intravenous administration of pentamidine isethionate (3.7 to 4 mg/kg/day infused over 4 hours) to 6 patients with aids being treated for pcp, the pharmacokinetic parameters obtained on days 1, 4 and 7 are summarized in the following table: mean ± sd cmax * ng/ml cmin * ng/ml clearance ml/min renal clearance ml/min/1.73 m 2 creatinine clearance ml/min/1.73 m 2 day 1 175.3 ± 54 --- 5737 ± 1878 269 ± 149 97 ± 12 day 4 210.9 ± 80 17.6 ± 9.5 3350 ± 1944 214 ± 145 93 ± 17 day 7 256.7 ± 89 40.8 ± 16.1 1989 ± 566 134 ± 60 69 ± 17 * derived from lidman compared to the mean auc on day 1, auc on day 4 and day 7 were about 2 and 3 fold higher, respectively, suggesting that steady state was not achieved by day 7 of dosing. in other published reports of pharmacokinetics of pentamidine following daily intravenous doses of 2 to 4 mg/kg/day, clearance ranged from 30 to 40 ml/min/kg and vdss ranged from 200 to 400 l/kg. reported values for terminal half-lives of 2.8 to 12 days is suggestive of a deep peripheral compartment. in the urine, up to 12% of the administered dose has been recovered during a dosing interval as unchanged pentamidine. tissue distribution was studied in mice given a single intraperitoneal injection of pentamidine at 10 mg/kg. the concentration was highest in the kidneys followed by the liver. in mice, pentamidine was excreted unchanged, primarily via the kidneys with some elimination in the feces. the ratio of amounts excreted in the urine and feces (4:1) was constant over the period of study. tissue distribution has also been studied in normal and in renally impaired dogs (n = 3 each) given 13 mg/kg of pentamidine iv, in 2 doses separated by five weeks. the concentration of pentamidine was highest in the liver followed by kidneys and lungs. pentamidine was concentrated in these organs approximately 70 to 1,000 times that of the peak serum concentration. similar findings were reported in normal and in renally impaired dogs (n = 2 each) given 97.5 mg/kg of pentamidine iv, in 15 daily doses. after repeated doses, the organs showed a further 3 to 7 fold accumulation while serum concentrations remained unchanged.

sation of the treatment. following multiple intravenous administration of pentamidine isethionate (3.7 to 4 mg/kg/day infused over 4 hours) to 6 patients with aids being treated for pcp, the pharmacokinetic parameters obtained on days 1, 4 and 7 are summarized in the following table: mean ± sd cmax * ng/ml cmin * ng/ml clearance ml/min renal clearance ml/min/1.73 m 2 creatinine clearance ml/min/1.73 m 2 day 1 175.3 ± 54 --- 5737 ± 1878 269 ± 149 97 ± 12 day 4 210.9 ± 80 17.6 ± 9.5 3350 ± 1944 214 ± 145 93 ± 17 day 7 256.7 ± 89 40.8 ± 16.1 1989 ± 566 134 ± 60 69 ± 17 * derived from lidman compared to the mean auc on day 1, auc on day 4 and day 7 were about 2 and 3 fold higher, respectively, suggesting that steady state was not achieved by day 7 of dosing. in other published reports of pharmacokinetics of pentamidine following daily intravenous doses of 2 to 4 mg/kg/day, clearance ranged from 30 to 40 ml/min/kg and vdss ranged from 200 to 400 l/kg. reported values for terminal half-lives of 2.8 to 12 days is suggestive of a deep peripheral compartment. in the urine, up to 12% of the administered dose has been recovered during a dosing interval as unchanged pentamidine. tissue distribution was studied in mice given a single intraperitoneal injection of pentamidine at 10 mg/kg. the concentration was highest in the kidneys followed by the liver. in mice, pentamidine was excreted unchanged, primarily via the kidneys with some elimination in the feces. the ratio of amounts excreted in the urine and feces (4:1) was constant over the period of study. tissue distribution has also been studied in normal and in renally impaired dogs (n = 3 each) given 13 mg/kg of pentamidine iv, in 2 doses separated by five weeks. the concentration of pentamidine was highest in the liver followed by kidneys and lungs. pentamidine was concentrated in these organs approximately 70 to 1,000 times that of the peak serum concentration. similar findings were reported in normal and in renally impaired dogs (n = 2 each) given 97.5 mg/kg of pentamidine iv, in 15 daily doses. after repeated doses, the organs showed a further 3 to 7 fold accumulation while serum concentrations remained unchanged.