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Pentamidine Isethionate
Pentamidine Isethionate For Injection Pentamidine Isethionate For Injection, an antiprotozoal agent, is a nonpyrogenic, lyophilized product. After reconstitution, it should be administered by intramuscular or intravenous (I.M. or I.V.) routes (see DOSAGE AND ADMINISTRATION). Pentamidine isethionate is a white, crystalline powder soluble in water and glycerin and insoluble in ether, acetone, and chloroform. It is chemically designated as 4,4'- diamidino-diphenoxypentane di (b-hydroxyethanesulfonate). The molecular forumula is C23H36N4O10S2 and the molecular weight is 592.68. Each vial contains: Pentamidine isethionate ...................................... 300 mg May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. Pentamidine Isethionate For Injection is prepared as a solution
and lyophilized in its final container.
Pentamidine isethionate, an aromatic diamidine, is known to have activity against Pneumocystis carinii. The mode of action of pentamidine is not fully understood. In vitro studies with mammalian tissues and the protozoan Crithidia oncopelti indicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. Preliminary studies have shown that in seven patients treated with daily I.M. doses of pentamidine at 4 mg/kg for 10 to 12 days, plasma concentrations were between 0.3 and 0.5 mcg/mL. The levels did not appreciably change with time after injection or from day to day. Higher plasma levels were encountered in patients with an elevated BUN. The patients continued to excrete decreasing amounts of pentamidine in urine up to six to eight weeks after cessation of the treatment. Tissue distribution
has been studied in mice given a single intraperitoneal injection
of pentamidine at
10 mg/kg. The concentration
in the kidneys was the highest followed by that in 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.
Pentamidine Isethionate For Injection is indicated for the treatment of pneumonia due to Pneumocystis carinii.
Pentamidine isethionate should be administered I.M. or I.V. only. The recommended regimen for adults and children is 4 mg/ kg once a day for 14 days. The benefits and risks of therapy with pentamidine isethionate for more than 14 days are not well defined. Intramuscular Injection The contents of one vial (300 mg) should be dissolved in 3 mL of Sterile Water for Injection. The calculated daily dose should then be withdrawn and administered by deep I.M. injection. Intravenous Injection The contents of one vial should first be dissolved in 3 to 5 mL of Sterile Water for Injection or Dextrose Injection 5%. The calculated dose of pentamidine isethionate should then be withdrawn and diluted further in 50 to 250 mL of Dextrose Injection 5%. The diluted I.V. 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. Intravenous infusion solutions of pentamidine isethionate at 1 mg and 2.5 mg/mL prepared in Dextrose Injection 5% are stable at room temperature for up to 24 hours. HOW SUPPLIED Pentamidine Isethionate For Injection is a sterile, lyophilized powder supplied in a single-dose, fliptop vial containing 300 mg of pentamidine isethionate packaged in individual cartons (List 4548). Store the dry product at controlled room temperature 15° to 30° C (59° to 86° F). Protect the dry product and reconstituted solution from light. Retain in carton until time of use. Discard unused portions. Caution: Federal (USA) law
prohibits dispensing without prescription.
CAUTION: Fatalities due to severe hypotension, hypoglycemia, acute pancreatitis and cardiac arrhythmias have been reported in patients treated with pentamidine isethionate, both by the I.M. and I.V. routes. The administration of the drug should, therefore, be limited to the patients in whom Pneumocystis carinii has been demonstrated. Of 424 patients treated with pentamidine isethionate, 244 (57.5%) developed some adverse reaction. Most of the patients had the acquired immunodeficiency syndrome (AIDS). In the following table, ''Severe'' refers to life- threatening reactions or reactions that required immediate corrective measures and led to discontinuation of pentamidine isethionate.
Fatalities due to severe hypotension,
hypoglycemia, acute
pancreatitis and cardiac
arrhythmias have been reported in patients treated with pentamidine
isethionate, both by the I.M.
and I.V. routes. Severe hypotension
may result after a single dose
(see Extravasations have been reported which, in some instances, proceeded to ulceration, tissue necrosis and or sloughing at the injection site. While not common, surgical debridement and skin grafting has been necessary in some of these cases; long- term sequelae have been reported. Prevention is the most effective means of limiting the severity of extravasation. The intravenous needle or catheter must be properly 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.
General Pentamidine isethionate should be used with caution in patients with hypertension, hypotension, hypoglycemia, hyperglycemia, hypocalcemia, leukopenia, thrombocytopenia, anemia, and hepatic or renal dysfunction. Patients may develop sudden, severe hypotension after a single dose of pentamidine isethionate, whether given I.V. or I.M. Therefore, patients receiving the drug should be lying down and the blood pressure should be monitored closely during administration of the drug and several times thereafter until the blood pressure is stable. Equipment for emergency resuscitation should be readily available. If pentamidine isethionate is administered I.V., it should be infused over a period of 60 minutes. Pentamidine isethionate- induced hypoglycemia has been associated with pancreatic islet cell necrosis and inappropriately high plasma insulin concentrations. Hyperglycemia and diabetes mellitus, with or without preceding hypoglycemia, have also occurred, sometimes several months after therapy with pentamidine isethionate. Therefore, blood glucose levels should be monitored daily during therapy with pentamidine isethionate, and several times thereafter. Laboratory Tests The following tests should be carried out before, during and after therapy:
Carcinogenesis, Mutagenesis, Impairment of Fertility No studies have been conducted to evaluate the potential of pentamidine isethionate as a carcinogen, mutagen, or cause of impaired fertility. Pregnancy Category C Animal reproduction
studies have not been conducted with pentamidine isethionate. It
is also not known whether pentamidine
isethionate can cause fetal harm when administered to a pregnant
woman or can affect
reproduction capacity. Pentamidine isethionate should be given to
a pregnant woman
only if clearly needed.
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