Pentamidine Isethionate warnings and precautions

# warnings and precautions

## Warnings
Fatalities due to severe hypotension, hypoglycemia, acute pancreatitis and cardiac arrhythmias have been reported in patients treated with pentamidine isethionate, both by the IM and IV routes.  Severe hypotension may result after a single IM or IV dose and is more likely with rapid IV administration (see PRECAUTIONS).  The administration of the drug should, therefore, be limited to the patients in whom Pneumocystis carinii has been demonstrated.  Patients should be closely monitored for the development of serious adverse reactions (see PRECAUTIONS and ADVERSE REACTIONS).
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.

## Precautions
- General
Pentamidine isethionate should be used with caution in patients with hypertension, hypotension, ventricular tachycardia, hypoglycemia, hyperglycemia, hypocalcemia, pancreatitis, leukopenia, thrombocytopenia, anemia, hepatic or renal dysfunction and Stevens-Johnson syndrome.
Patients may develop sudden, severe hypotension after a single dose of pentamidine isethionate, whether given IV or IM.  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 IV, it should be infused over a period of 60 to 120 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.
Renal and Hepatic Impairment
The efficacy or safety of alternative Pentam 300 dosing protocols have not been established for patients with impaired renal or hepatic function.
Laboratory Tests
The following tests should be carried out before, during and after therapy:
a) Daily blood urea nitrogen and serum creatinine determinations.
b) Daily blood glucose determinations.
c) Complete blood count and platelet count.
d) Liver function test, including serum bilirubin, alkaline phosphatase, AST (SGOT), and ALT (SGPT).
e) Serum calcium determinations.
f) Electrocardiograms.
Drug Interactions
No drug interaction studies with Pentam 300 have been conducted.
Because the nephrotoxic effects may be additive, the concomitant or sequential use of pentamidine isethionate and other nephrotoxic drugs such as aminoglycosides, amphotericin B, cisplatin, foscarnet, or vancomycin should be closely monitored and avoided, if possible.
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-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 not be given to a pregnant woman unless the potential benefits are judged to outweigh the unknown risks.
Nursing Mothers
It is not known whether pentamidine isethionate is excreted in human milk.  Because of the potential for serious adverse reactions in nursing infants from pentamidine isethionate, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.  Because many drugs are excreted in human milk, pentamidine isethionate should not be given to a nursing mother unless the potential benefits are judged to outweigh the unknown risks.
Pediatric Use
Intravenous and intramuscular pentamidine has been described as an effective treatment for Pneumocystis carinii pneumonia (PCP) in immunocompromised pediatric patients beyond 4 months of age.  The efficacy and safety profiles in these pediatric patients were similar to those observed in adult patients (See DOSAGE AND ADMINISTRATION and OVERDOSAGE).