DBL Pentamidine Isethionate

DBL Pentamidine Isethionate

pentamidine isetionate

Manufacturer:

Pfizer

Distributor:

Zuellig Pharma

Marketer:

DKSH
Full Prescribing Info
Contents
Pentamidine isethionate.
Description
Each 4 mg of pentamidine isethionate is equivalent to 2.3 mg pentamidine base.
DBL Pentamidine Isethionate for Injection is a white or almost white, odourless or almost odourless hygroscopic powder.
Action
Pharmacology: Pentamidine isethionate exhibits antiprotozoal activity against Pneumocystis carinii, Leishmania and some species of Trypanosoma.
The exact mechanism of antiprotozoal action of pentamidine has not been fully elucidated. Several mechanisms of action may be involved, and the role of the mechanism(s) may vary among the different types of protozoa (e.g. trypanosome, sporozoons). Most information on the antiprotozoal activity of pentamidine has been derived from studies involving trypanosomes. In vitro studies indicate that the drug interferes with nuclear metabolism.
Pharmacokinetics: Limited information is available concerning the pharmacokinetics of pentamidine isethionate.
Following a single 4 mg/kg IV dose of pentamidine isethionate (given as a 2 hour infusion), peak plasma pentamidine concentrations averaged 612 nanogram/mL after completion of the IV infusion.
Distribution: Distribution of pentamidine into human body tissues and fluids has not been well characterised, but the drug appears to be rapidly and extensively distributed and/or bound to tissues. Pentamidine has a distribution half life of 5 to 15 minutes after intravenous administration. Following parenteral administration, highest concentrations have been found in the liver, followed by the kidneys, adrenals, spleen, lungs and pancreas. Pentamidine penetrates the CNS only very poorly after prolonged therapy.
In vitro, pentamidine is reportedly 69% bound to serum proteins.
It is not known whether pentamidine isethionate crosses the placenta or is distributed into breast milk.
Elimination: Little is known about the elimination in humans. Plasma concentrations of pentamidine have been found to decline in a biphasic manner following a single IV infusion in patients with normal renal function. The mean elimination half life was found to be 18 minutes in the initial phase and 6.4 hours in the terminal phase. Pentamidine appears to be eliminated very slowly from tissues in which the drug principally accumulates (e.g. liver, lungs). The half life of pentamidine may be prolonged in patients with impaired renal function, however no correlation between renal function and plasma clearance of pentamidine has been found. It is not known if the drug is excreted in faeces.
Only a small amount (approximately 6%) of the administered dose is excreted unchanged in the urine over a 15 day period.
Following a single 4 mg/kg IV dose of pentamidine isethionate in patients with AIDS or pneumocystis pneumonia who had normal renal function, about 2.5 to 5% of the dose was excreted in urine as unchanged drug over 24 hours, mainly within the first 8 hours after administration. Similar amounts (about 1 to 4% of the dose) were also excreted in urine as unchanged drug in 24 hours in patients with mild to moderate renal impairment.
Limited data suggest that pentamidine is not appreciably removed by haemodialysis or peritoneal dialysis.
Microbiology: Pentamidine isethionate exhibits antiprotozoal activity against Pneumocystis carinii, Leishmania and some species of Trypanosoma.
Indications/Uses
Pentamidine isethionate is indicated for intravenous administration in the treatment of the following conditions: As an alternative first line treatment for Pneumocystis carinii infection in AIDS patients; As second line treatment for Pneumocystis carinii infection in non-AIDS patients; As second line treatment of Leishmaniasis (visceral and cutaneous), except Leishmania aethiopica where it may be used as first line therapy; As second line treatment for Trypanosomiasis (except for the Trypanosomiasis rhodesiense strain due to lack of efficacy).
Dosage/Direction for Use
DBL Pentamidine Isethionate for Injection should be given as a slow IV infusion with a patient in a supine position in order to reduce the incidence of sudden severe hypotension. Direct bolus intravenous injection or rapid administration must not be used.
Reconstitution: The contents of a 300 mg vial should be dissolved in 3 mL to 5 mL of Water for Injections. The required dose of Pentamidine Isethionate should then be diluted further in 50 to 250 mL of Glucose Intravenous Infusion 5% or Sodium Chloride Intravenous Infusion 0.9%. The reconstituted solutions should be visually examined before use. Any solutions which are hazy, discoloured or contain visible particulate matter should not be used. Diluted solutions containing Pentamidine Isethionate should be infused over a period of at least 60 minutes under close medical supervision, whilst the patient is kept lying down.
Dosage: The following dosage regimens are recommended: P. carinii pneumonia: 4 mg/kg bodyweight Pentamidine Isethionate once daily for 14 days, preferably by slow intravenous infusion.
Leishmaniasis: On the basis of current knowledge the following dosage are suggested, however, the optimal treatment regimen has yet to be established.
Visceral (Kala-azar): 3 to 4 mg/kg body weight Pentamidine Isethionate on alternate days (3 times a week) to a maximum of 10 injections.
Cutaneous: 3 to 4 mg/kg bodyweight Pentamidine Isethionate once or twice weekly, until the condition resolves.
Trypanosomiasis: (Haemolymphete stage only).
4 mg/kg bodyweight Pentamidine Isethionate daily or on alternate days to a total of 7 to 10 injections.
Impaired renal function (creatinine clearance <35 mL/min): There is little information on the kinetics or the adverse effects profile of pentamidine in patients with impaired renal function.
Impaired hepatic function: No information available.
Overdosage
There is no information available concerning the treatment of overdosage. There is no specific antidote. In general, overdosage would be expected to produce effects that are an extension of common adverse effects or of the serious metabolic sequelae observed. Treatment should be symptomatic.
Contraindications
Patients with known hypersensitivity to pentamidine.
Pentamidine should not be administered to patients who are pregnant or breastfeeding unless considered essential by the physician.
Warnings
Severe, sometimes fatal, hypotension, hypoglycaemia, pancreatitis and cardiac arrhythmias have been reported. Other life threatening reactions requiring immediate corrective measures and withdrawal of treatment have included leucopenia (less than 1,000 per cubic millimetre), thrombocytopenia (less than 20,000 per cubic mm), acute renal failure, hypocalcaemia, and ventricular tachycardia. A possible case of Stevens-Johnson syndrome has been reported.
Fatalities have been documented following pentamidine administration. The ratio of therapeutic to toxic dose of pentamidine is very low and adverse effects, some of which may be life threatening, occur frequently during its use. Pentamidine should therefore be used only for the approved indications in a hospital where close observation can be maintained.
Special Precautions
Pentamidine isethionate should be used with caution in patients with the following: Malnutrition; Hyperglycaemia or hypoglycaemia; Hepatic dysfunction; Renal dysfunction; Hypertension or hypotension; Anaemia, leucopenia or thrombocytopenia.
Laboratory monitoring as follows should be performed before, during and after treatment.
Blood urea nitrogen and serum creatinine daily during therapy.
Complete blood and platelet counts daily during therapy.
Fasting blood glucose measurements should be taken before, daily during therapy, and at regular intervals after completion of therapy. Hyperglycaemia and diabetes mellitus, with or without preceding hypoglycaemia, have occurred up to several months after cessation of therapy.
Liver function tests (LFTs) including serum bilirubin, alkaline phosphatase, aspartate aminotransferase (AST/SGOT), and alanine aminotransferase (ALT/SGPT). If baseline measurements are normal and remain so during therapy, test weekly thereafter. When there is baseline elevation in LFTs or LFTs increase during therapy, continue monitoring weekly unless the patient is on other hepatotoxic agents, when monitoring every 3 to 5 days is appropriate.
Serum calcium, test weekly.
Urine analysis and serum electrolytes daily during therapy.
Electrocardiograms at regular intervals.
Sudden, severe hypotension may occur in patients following a single IV dose of pentamidine. The patient should receive the medicine lying down. The baseline blood pressure should be established before the first dose and the blood pressure closely monitored during administration and at hourly intervals after the first dose until stable. Blood pressure should be monitored 4 or 5 times daily until treatment is concluded.
Use in pregnancy (Category B3): Pentamidine has been found to cross the placenta in rats given high doses late in pregnancy. Studies in rabbits have also shown pentamidine to be mildly embryotoxic, with an increase in post-implantation losses and delayed foetal ossification at doses of 1, 3 and 8 mg/kg of body weight.
It is not known whether pentamidine isethionate crosses the placenta or causes foetal harm when administered to pregnant women; therefore, pentamidine is contraindicated during pregnancy and should only be used when considered essential.
Category B3: Drugs which have been taken by only by a limited number of pregnant women and women of child bearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
Use in lactation: Since it is not known whether pentamidine isethionate is distributed into milk, the medicine is contraindicated during lactation and should only be administered to nursing mothers when considered essential.
Use in children: Very little information is available concerning the safe use of pentamidine in children.
Use in the elderly: There is no information on the safe use of pentamidine in the elderly.
Use In Pregnancy & Lactation
Use in pregnancy (Category B3): Pentamidine has been found to cross the placenta in rats given high doses late in pregnancy. Studies in rabbits have also shown pentamidine to be mildly embryotoxic, with an increase in post-implantation losses and delayed foetal ossification at doses of 1, 3 and 8 mg/kg of body weight. It is not known whether pentamidine isethionate crosses the placenta or causes foetal harm when administered to pregnant women; therefore, pentamidine is contraindicated during pregnancy and should only be used when considered essential.
Category B3: Drugs which have been taken by only by a limited number of pregnant women and women of child bearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
Use in lactation: Since it is not known whether pentamidine isethionate is distributed into milk, the medicine is contraindicated during lactation and should only be administered to nursing mothers when considered essential.
Adverse Reactions
Life-threatening reactions: severe hypotension; severe hypoglycaemia; acute pancreatitis; cardiac arrhythmias and cardiac arrest; syncope; ventricular tachycardia; leucopenia (less than 1,000 cells per cubic millimetre); thrombocytopenia (less than 20,000 cells per cubic millimetre); acute renal failure; hypocalcaemia; Stevens-Johnson syndrome (single possible case); toxic delirium; Herxheimer reaction.
The previously mentioned adverse effects can be severe, sometimes fatal, and require immediate corrective measures and withdrawal of treatment.
Other reactions: azotaemia, increased creatinine levels, albuminuria; abnormal liver function tests; anaemia, leucopenia and thrombocytopenia; hyperkalaemia, hyponatraemia; nausea and vomiting; diabetes mellitus; hyperglycaemia or hypoglycaemia; dizziness, hypotension; flushing; rash; taste disturbances; local reactions at the injection site including thrombophlebitis; tachycardia, bradycardia; breathlessness.
Drug Interactions
The nephrotoxic effects of pentamidine isethionate when given concomitantly with other nephrotoxic drugs, or sequentially, may be additive.
Incompatibilities: After reconstitution with Water for Injections, DBL Pentamidine Isethionate for Injection should not be mixed with any injection solution other than Glucose Intravenous Infusion 5% or Sodium Chloride Intravenous Infusion 0.9%.
Caution For Usage
Compatibilities: Reconstituted solutions at concentrations of 100 mg/mL and 60 mg/mL are chemically stable for 48 hours when stored at 2 to 8°C and room temperature under fluorescent light. DBL Pentamidine Isethionate for Injection BP when reconstituted with Water for Injections and diluted to 1.0 mg/mL and 2.5 mg/mL in Sodium Chloride Intravenous Infusion 0.9% and Glucose Intravenous Infusion 5% retained its potency for at least 48 hours when stored under fluorescent light at 21 ± 2°C. However, to avoid microbial contamination, the prepared solution should be used within 24 hours.
Storage
Store below 30°C.
ATC Classification
P01CX01 - pentamidine isethionate ; Belongs to the class of other agents used in the treatment of leishmaniasis and trypanosomiasis.
Presentation/Packing
Powd for inj 4 mg/mL (white or almost white, odourless or almost odourless hygroscopic powder in vial) x 75 mL x 1's.
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