Consumer medicine information

DBL Pentamidine Isethionate for Injection

Pentamidine isetionate

BRAND INFORMATION

Brand name

DBL Pentamidine Isethionate for Injection

Active ingredient

Pentamidine isetionate

Schedule

SUMMARY CMI

DBL™ Pentamidine Isethionate

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using DBL Pentamidine Isethionate?

DBL Pentamidine Isethionate contains the active ingredient pentamidine isetionate. DBL Pentamidine Isethionate is used to treat an infection called pneumocystis carinii pneumonia (PCP). DBL Pentamidine Isethionate can also be used to treat other types of protozoal infections, such as Leishmaniasis and Trypanosomiasis.

For more information, see Section 1. Why am I using DBL Pentamidine Isethionate? in the full CMI.

2. What should I know before I use DBL Pentamidine Isethionate?

Do not use if you have ever had an allergic reaction to pentamidine or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions or take any other medicines.

DBL Pentamidine Isethionate is Pentamidine is not recommended for use during pregnancy or breastfeeding. Speak to your doctor if you are pregnant, plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use DBL Pentamidine Isethionate? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DBL Pentamidine Isethionate and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use DBL Pentamidine Isethionate?

DBL Pentamidine Isethionate must only be given by a doctor or nurse. Your doctor will decide what dose of pentamidine you will receive.
DBL Pentamidine Isethionate is given as a slow injection into a vein (intravenously) over a period of at least 60 minutes.

More instructions can be found in Section 4. How do I use DBL Pentamidine Isethionate? in the full CMI.

5. What should I know while using DBL Pentamidine Isethionate?

Things you should do	If you become pregnant, or which to breastfeed, while being given pentamidine, tell your doctor immediately. Remind any doctor or dentist you visit that you are using DBL Pentamidine Isethionate. If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are being given pentamidine.
Driving or using machines	DBL Pentamidine Isethionate may cause dizziness and light-headedness in some people.
Drinking alcohol	Alcohol may worsen dizziness or light-headedness.
Looking after your medicine	DBL Pentamidine Isethionate will generally be stored in the pharmacy or on the ward.

For more information, see Section 5. What should I know while using DBL Pentamidine Isethionate? in the full CMI.

6. Are there any side effects?

Side effects may include nausea and vomiting, taste disturbance or metallic taste, pain or redness at the injection site, flushing of the skin or itching, hair loss, or hallucinations. More serious side effects may include sings of an infection such as sore throat, fever and muscle pain, unusual bleeding or bruising, dizziness or fainting, other changes to blood pressure or changes in urine.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

DBL™ Pentamidine Isethionate

Active ingredient(s): Pentamidine Isetionate (pen-TAM-i-deen eye-se-THIO-nate)

Consumer Medicine Information (CMI)

This leaflet provides important information about using DBL Pentamidine Isethionate. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using DBL Pentamidine Isethionate.

Where to find information in this leaflet:

1. Why am I using DBL Pentamidine Isethionate?
2. What should I know before I use DBL Pentamidine Isethionate?
3. What if I am taking other medicines?
4. How do I use DBL Pentamidine Isethionate?
5. What should I know while using DBL Pentamidine Isethionate?
6. Are there any side effects?
7. Product details

1. Why am I using DBL Pentamidine Isethionate?

DBL Pentamidine Isethionate contains the active ingredient pentamidine isetionate. DBL Pentamidine Isethionate is used to treat an infection called pneumocystis carinii pneumonia (PCP). This kind of pneumonia occurs commonly in patients whose immune system is not working normally, such as cancer patients, transplant patients, or patients with acquired immune deficiency syndrome (AIDS).

DBL Pentamidine Isethionate can also be used to treat other types of protozoal infections, such as Leishmaniasis and Trypanosomiasis.

2. What should I know before I use DBL Pentamidine Isethionate?

Warnings

Do not use DBL Pentamidine Isethionate if:

you are allergic to pentamidine, or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to pentamidine may include:

shortness of breath, wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin.

Always check the ingredients to make sure you can use this medicine.

you are pregnant or intend to become pregnant. Please see ‘pregnancy and breastfeeding’ below.
you are breast-feeding or plan to breast-feed. Please see ‘pregnancy and breastfeeding’ below.

Check with your doctor if you:

Have any other medical conditions, especially:
malnutrition
high or low blood sugar levels
liver problems
kidney problems
heart problems
blood pressure problems (high or low blood pressure)
low numbers of red blood cells, white blood cells, or platelets.

This medicine may cause serious reactions, sometimes leading to death, including:

very low blood pressure, even after one dose
very low blood sugar
irregular heartbeat
inflamed pancreas

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Pentamidine is not recommended for use during pregnancy. If there is a need to consider pentamidine during your pregnancy, your doctor will discuss with you the benefits and risks of being given it.

Pentamidine is not recommended while you are breast-feeding, as it is not known whether pentamidine passes into breast milk. If there is a need to consider pentamidine while you are breast-feeding, your doctor will discuss with you the benefits and risks of being given it.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with DBL Pentamidine Isethionate and affect how it works. These include:

amphotericin B, a drug used to treat serious fungal infections
aminoglycoside antibiotics, such as gentamicin
cisplatin, a drug used to treat certain types of cancer
vancomycin, a type of antibiotic

Medicines that are harmful to the liver, kidneys or blood cells may also interfere with pentamidine.

These medicines may be affected by pentamidine or may affect how well it works. You may need different amounts of your medicine, or you may need to take/use different medicines. Your doctor or pharmacist will advise you.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DBL Pentamidine Isethionate.

4. How do I use DBL Pentamidine Isethionate?

How much is given

Your doctor will decide what dose of pentamidine you will receive. This depends on your condition and other factors, such as your weight.

How DBL Pentamidine Isethionate is given and for how long

DBL Pentamidine Isethionate is given as a slow injection into a vein (intravenously) over a period of at least 60 minutes. DBL Pentamidine Isethionate must only be given by a doctor or nurse.
Some patients develop sudden, severe low blood pressure after a dose of pentamidine. Therefore, you should be lying down while you are being given pentamidine. Your blood pressure will be closely monitored.
To treat Pneumocystis carinii pneumonia (PCP), DBL Pentamidine Isethionate is usually given once daily for 14 days.
To treat Leishmaniasis, DBL Pentamidine Isethionate may be given once, twice or three times a week.
To treat Trypanosomiasis, DBL Pentamidine Isethionate may be given either daily or on alternate days for a total of 7 to 10 doses.

If you are given too much DBL Pentamidine Isethionate

As DBL Pentamidine Isethionate is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any severe side effects after being given this medicine, or if you think that you have received too much DBL pentamidine isethionate, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using DBL Pentamidine Isethionate?

Things you should do

If you become pregnant, or wish to breastfeed, while being given pentamidine, tell your doctor immediately.
If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are being given pentamidine.
Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do some tests (such as blood and platelet counts, blood sugar, heart rate, kidney and liver function tests) from time to time to make sure the medicine is working and to prevent unwanted side effects

Call your doctor straight away if you:

Experience any unusual effects of this medicine, or any side effects listed under Section 6. ‘Are there any side effects’ below.

Remind any doctor or dentist you visit that you are using DBL Pentamidine Isethionate.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DBL Pentamidine Isethionate affects you.

DBL Pentamidine Isethionate may cause dizziness and light-headedness in some people.

Make sure you know how you react to pentamidine before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may worsen dizziness or light-headedness.

Looking after your medicine

DBL Pentamidine Isethionate will generally be stored in the pharmacy or on the ward

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

Gastrointestinal related symptoms:

nausea and vomiting
taste disturbances, metallic taste

Visible skin related changes:

pain or redness at the injection site
skin rash, redness, itching
flushing in face

Other

hair loss
hallucinations

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

Changes to the skin:

unusual bleeding or bruising
peeling of the skin

Signs of an infection or reaction:

sore throat or fever
fever, chills, headache and muscle pain (signs of Herxheimer reaction)

Changes to blood sugar:

increased urination, unusual thirst, tiredness (signs of high blood sugar)
trembling or shaking, light-headedness, irritability (signs of low blood sugar)

Blood pressure, heart rate or clothing:

dizziness or fainting (may be signs of low blood pressure)
slow, fast or irregular heart rate
pain, swelling, redness, skin tenderness, warmth, sudden shortness of breath, chest pain (signs of blood clot)

Breathing:

breathlessness, difficulty in breathing.

Urine changes and associated swelling:

less urine, change in the colour of your urine with swelling in your legs, ankles or feet

Other:

pain in upper abdomen

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What DBL Pentamidine Isethionate contains

Active ingredient (main ingredient)	Pentamidine isetionate
Other ingredients (inactive ingredients)	There are no other ingredients.

Do not take this medicine if you are allergic to any of these ingredients.

DBL Pentamidine Isethionate does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes

What DBL Pentamidine Isethionate looks like

DBL Pentamidine Isethionate is a white or almost white powder. It must be dissolved and further diluted before it is given.

300 mg per vial - AUST R 16260

Who distributes DBL Pentamidine Isethionate

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

This leaflet was prepared in June 2022.

Published by MIMS August 2022

BRAND INFORMATION

Brand name

DBL Pentamidine Isethionate for Injection

Active ingredient

Pentamidine isetionate

Schedule

1 Name of Medicine

Pentamidine isetionate.

2 Qualitative and Quantitative Composition

Each vial of DBL Pentamidine Isethionate for Injection contains 300 mg pentamidine isetionate as a freeze dried powder or plug.
Each 4 mg of pentamidine isetionate is equivalent to 2.3 mg pentamidine base.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Powder for injection.
DBL Pentamidine Isethionate for Injection is a white or almost white, odourless or almost odourless hygroscopic powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Pentamidine isetionate 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).

4.2 Dose and Method of Administration

Dosage.

The following dosage regimens are recommended.
P. carinii pneumonia. 4 mg/kg bodyweight pentamidine isetionate 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 bodyweight pentamidine isetionate on alternate days (3 times a week) to a maximum of 10 injections.

Cutaneous.

3 to 4 mg/kg bodyweight pentamidine isetionate once or twice weekly, until the condition resolves.
Trypanosomiasis. Haemolymphete stage only.
4 mg/kg bodyweight pentamidine isetionate daily or on alternate days to a total of 7 to 10 injections.

Dosage adjustment.

Renal impairment.

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.

Hepatic impairment.

No information available.

Method of administration.

DBL Pentamidine Isethionate for Injection should be given as a slow intravenous 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 isetionate 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 isetionate should be infused over a period of at least 60 minutes under close medical supervision, whilst the patient is kept lying down.

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 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.

4.3 Contraindications

Patients with a known hypersensitivity to pentamidine.
Pentamidine should not be administered to patients who are pregnant or breastfeeding unless considered essential by the physician.

4.4 Special Warnings and Precautions for Use

Serious warnings and precautions.

Severe, sometimes fatal, hypotension, hypoglycaemia, acute pancreatitis, renal impairment 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 millimetre), 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 isetionate for injection should be used only in a hospital setting with facilities to monitor blood glucose, blood count, renal function and hepatic function. Electrocardiograms should be carried out at regular intervals (see Section 4.4 Special Warnings and Precautions for Use, Monitoring and laboratory tests).
Extravasation reactions may result in ulceration, tissue necrosis and long-term sequelae (see Section 4.8 Adverse Effects (Undesirable Effects)).
DBL Pentamidine is not approved for inhaled use. Bronchospasm has been reported to occur following the use of inhaled product (see Section 4.8 Adverse Effects (Undesirable Effects)). This has been particularly noted in patients who have a history of smoking or asthma. This can be controlled by prior use of bronchodilators.
Pentamidine isetionate should be used with caution in patients with the following:
1. Malnutrition.
2. Hyperglycaemia or hypoglycaemia.
3. Hepatic dysfunction.
4. Renal dysfunction.
5. Hypertension or hypotension.
6. Anaemia, leucopenia or thrombocytopenia.

General.

Pentamidine isetionate for injection should only be administered under close medical supervision, and the patient should be very carefully monitored for the development of serious adverse reactions (see Section 4.8 Adverse Effects (Undesirable Effects)).
The administration of pentamidine isetionate for injection should be limited to patients in whom Pneumocystis jirovecii infection has been confirmed.
Some patients may become nauseated or develop fever after taking each dose of pentamidine isetionate for injection. In such cases, the prophylactic use of an antiemetic and/or paracetamol may be considered.

Cardiovascular.

Patients may develop sudden, severe hypotension after receiving a single intramuscular or intravenous dose of pentamidine isetionate. Therefore, patients receiving pentamidine isetionate for injection should be in a supine position and the blood pressure 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. Pentamidine isetionate for injection should be infused over a period of at least 60 minutes to minimise the risk of hypotension.
Severe hypotension with accompanying bradycardia has been observed in a patient after the sixth dose of pentamidine isetionate. This hypotension did not respond to intravenous colloids, graded compression stockings or corticosteroids but resolved within four days of stopping treatment.
Ventricular tachycardia and ECG abnormalities (including QT interval prolongation and torsades de pointes) may develop in patients receiving pentamidine isetionate. ECG's may be required at regular intervals if signs of cardiotoxicity develop.

Endocrine and metabolism.

Pentamidine isetionate can produce hypoglycaemia, which may be severe, life-threatening and/or prolonged. It generally occurs after 5 to 7 days of therapy but can even occur up to several days after the drug is discontinued. The duration appears quite variable, persisting for one day to several weeks. Pentamidine isetionate-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 termination of therapy with pentamidine isetionate.
Hypoglycaemia induced by pentamidine isetionate may be controlled by intravenous administration of dextrose or (oral) diazoxide, but it is not known if such therapy can prevent the subsequent development of diabetes mellitus.

Gastrointestinal.

Cases of nausea and vomiting have been observed with pentamidine isetionate treatment.

Haematologic.

Leucopenia and thrombocytopenia, which can be severe (e.g. leucocyte count less than 1,000 per cubic millimetre, platelet count less than 20,000 per cubic millimetre), occur occasionally in patients receiving pentamidine isetionate. Cases of anaemia have been observed. In a few cases, pentamidine isetionate therapy has been associated with neutropenia.

Hepatic/biliary/pancreatic.

Abnormal liver function tests may occur. Liver function should be routinely monitored in patients receiving pentamidine isetionate for injection (see Section 4.4 Special Warnings and Precautions for Use, Monitoring and laboratory tests). Cases of acute pancreatitis have been observed with pentamidine isetionate treatment.

Immune.

Hypersensitivity reactions at the injection site, such as skin rash and erythema, may occur (see Section 4.4 Special Warnings and Precautions for Use, Skin; Section 4.8 Adverse Effects (Undesirable Effects)).

Skin.

Intramuscular injections are often associated with pain, tenderness, erythema, and induration at the site of injection. Sterile abscesses have been observed. Therefore, intramuscular administration should be reserved for patients with adequate muscle mass and limited to the rare situations where intravenous infusion is not feasible.

Vascular.

Phlebitis can occur after intravenous injection.

Monitoring and laboratory tests.

In order to monitor for possible toxicity, the following tests should be performed before, during and after treatment.
1. Blood urea nitrogen and serum creatinine daily during therapy.
2. Complete blood and platelet counts daily during therapy.
3. 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.
4. 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.
5. Serum calcium, test weekly.
6. Urine analysis and serum electrolytes daily during therapy.
7. Electrocardiograms at regular intervals.

Use in renal impairment.

Severe renal impairment resulting in death may also occur in the presence of various clinical complications (e.g. bacterial sepsis), concurrent administration of other nephrotoxic antibiotic agents or previous evidence of renal disease.

Use in the elderly.

There is no information on the safe use of pentamidine in the elderly.

Paediatric use.

The safety and efficacy of pentamidine isetionate for injection has not been established in the paediatric population, and pharmacokinetic data are extremely limited.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Since nephrotoxic effects may be additive, the concurrent or sequential use of pentamidine isetionate with drugs having a nephrotoxic potential (e.g. aminoglycosides, amphotericin B, cisplatin, methoxyflurane or vancomycin) should be undertaken with caution. Pentamidine isetionate for injection should be administered with caution to patients who are receiving drugs with hepatotoxic potential or medication that can impair the haematopoietic system.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing 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.
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 postimplantation losses and delayed fetal ossification at doses of 1, 3 and 8 mg/kg of bodyweight.
It is not known whether pentamidine isetionate crosses the placenta or causes fetal harm when administered to pregnant women; therefore, pentamidine is contraindicated during pregnancy and should only be used when considered essential.
Since it is not known whether pentamidine isetionate is distributed into milk, the medicine is contraindicated during lactation and should only be administered to nursing mothers when considered essential.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Fatalities due to severe hypotension, hypoglycemia, acute pancreatitis, renal impairment and cardiac arrhythmias have been reported in patients treated with pentamidine isetionate.

Life threatening reactions.

Blood and lymphatic system disorders.

Leucopenia (less than 1,000 cells per cubic millimetre), thrombocytopenia (less than 20,000 cells per cubic millimetre).

Immune system disorders.

Herxheimer reaction.

Metabolism and nutrition disorders.

Severe hypoglycaemia, hypocalcaemia.

Psychiatric disorders.

Toxic delirium.

Nervous system disorders.

Syncope.

Cardiac disorders.

Cardiac arrhythmias and cardiac arrest (including QT interval prolongation and torsade de pointes), ventricular tachycardia.

Vascular disorders.

Severe hypotension.

Gastrointestinal disorders.

Acute pancreatitis.

Skin and subcutaneous tissue disorders.

Stevens-Johnson syndrome (single possible case).

Renal and urinary disorders.

Acute renal failure.
The above mentioned adverse effects can be severe, sometimes fatal, and require immediate corrective measures and withdrawal of treatment.

Other reactions.

Other adverse reactions reported are listed in this section per MedDRA system organ class.

Blood and lymphatic system disorders.

Anaemia, thrombocytopenia, leucopenia.

Metabolism and nutrition disorders.

Hypocalcaemia, hypoglycaemia, hyperglycaemia, hyperkalaemia, hyponatraemia, diabetes mellitus.

Psychiatric disorders.

Hallucinations.

Nervous system disorders.

Taste disturbances, dizziness, syncope.

Cardiac disorders.

Tachycardia, bradycardia.

Vascular disorders.

Hypotension, facial flushing, venous thrombosis.

Respiratory, thoracic and mediastinal disorders.

Breathlessness.
Local reactions ranging in severity from cough, breathlessness, wheezing, bronchospasms (with inhaled use), particularly in patients with a history of smoking or asthma, which can usually be controlled by prior use of bronchodilator.

Gastrointestinal disorders.

Nausea, vomiting.

Hepatobiliary disorders.

Abnormal liver function (hepatic dysfunction).

Skin and subcutaneous tissue disorders.

Abscess and/or necrosis, rash, itching, alopecia, erythema multiforme.

Renal and urinary disorders.

Azotaemia, albuminuria, glycosuria, increased creatinine levels.

General disorders and administration site conditions.

Local reactions at the injection site including abscess, pain, thrombophlebitis.

Investigations.

Depressed serum folate.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

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 and supportive. Neither peritoneal dialysis nor haemodialysis appear to remove the drug rapidly enough to cause a precipitous decline in the plasma concentration of pentamidine isetionate.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pentamidine isetionate 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, sporozoans). 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.

Microbiology.

Pentamidine isetionate exhibits antiprotozoal activity against Pneumocystis carinii, Leishmania and some species of Trypanosoma.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Limited information is available concerning the pharmacokinetics of pentamidine isetionate.

Absorption.

Following a single 4 mg/kg IV dose of pentamidine isetionate (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 isetionate crosses the placenta or is distributed into breast milk.

Excretion.

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 isetionate 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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 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%.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

DBL Pentamidine Isethionate for Injection is available in 1 vial.
Strength: 300 mg/vial.
Pack size: 1's.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

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DBL Pentamidine Isethionate for Injection

Pentamidine isetionate

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