Drugs List

Therapeutic Indications

Uses

Leishmaniasis
Pneumocystis jiroveci pneumonia
Prophylaxis of pneumocystis jiroveci pneumonia in HIV patients
Trypanosomiasis

Prophylaxis of Pneumocystis jiroveci pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV) who have had a previous episode of PCP. Administration is by inhalation route.

Administration

For intravenous infusion, deep intramuscular injection or inhalation.

Contraindications

Neonates under 1 month

Precautions and Warnings

Predisposition to pneumothorax
Tobacco smoking
Anaemia
Asthma
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Hepatic impairment
History of ventricular arrhythmias
Hyperglycaemia
Hypertension
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hypotension
Ischaemic heart disease
Leucopenia
Pregnancy
Renal impairment
Thrombocytopenia

Advise patient dizziness may affect ability to drive or operate machinery
Keep patient supine when receiving injection
Staff: Not to be handled by pregnant staff
Monitor blood pressure before starting treatment
Monitor serum electrolytes before and during treatment
Perform liver function tests before commencing therapy and during therapy
If QTc >550msec during therapy, consider alternative regimen
If QTc>500msec during therapy, continuous cardiac monitoring is required
Monitor blood and platelet counts daily during therapy
Monitor blood pressure
Monitor blood urea nitrogen and serum creatinine daily
Monitor cardiac function by ECG
Monitor fasting blood glucose daily, and regularly after therapy completion
Monitor serum calcium weekly
Monitor serum magnesium twice weekly
Perform urine analysis daily during treatment

Take baseline measurements of liver function tests (LFTs), including bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alkaline aminotransferase (ALT). Test weekly if baseline measurements are normal.
If there is baseline elevation of LFTs or LFTs increase during therapy, continue to monitor weekly unless the patient is receiving concurrent hepatotoxic drugs, when monitoring every 3 - 5 days is appropriate.

Hyperglycaemia with or without preceding hypoglycaemia have occurred up to several months after cessation of therapy. Monitor fasting blood glucose daily during therapy and at regular intervals after cessation of therapy.

The use of aerosolised therapy in patients at high risk of a pneumothorax should be weighed against the clinical consequences of such a manifestation.

Bronchospasm has been reported following nebulised administration. Patients with a history of smoking or asthma seem to be at greater risk. Prior use of bronchodilators can help to control this effect.

Pregnancy and Lactation

Pregnancy

Pentamidine isetionate should not be used during pregnancy unless considered essential. Safety of use during pregnancy has not been established.

A miscarriage during the first trimester has been reported while using aerosolised pentamidine for prophylactic use.

Bystanders, including medical personnel, women of child bearing potential and pregnant women should avoid atmospheric exposure to pentamidine from nebuliser usage.

Animal studies conducted with rats using human equivalent doses showed embryotoxicity but no teratogenic effects. These doses were embryocidal when administered during embryogenesis. Significant placental transfer was observed in rats administered pentamidine in late pregnancy.

Schaefer (2007) concludes that pentamidine should only be administered to pregnant women in cases of life threatening infections when other antibiotics have been ineffective. Inadvertent use does not warrant the termination of pregnancy or the employment of invasive prenatal diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pentamidine isetionate should not be used during breastfeeding unless considered essential.

There are no reports available on the use of pentamidine during breastfeeding via any route. The levels of pentamidine in breast milk after administration via nebulisation are probably nil.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Abscess formation (injection site)
Acute renal failure
Anaemia
Arrhythmias
Azotaemia
Bronchospasm (on inhalation)
Cough
Decreased appetite
Dizziness
Eosinophilic pneumonia
Fatigue
Fever
Flushing
Hyperglycaemia
Hyperkalaemia
Hypocalcaemia
Hypoglycaemia
Hypomagnesaemia
Hypotension
Induration (injection site)
Leucopenia
Light-headedness
Macroscopic haematuria
Nausea
Necrosis (injection site)
Pain on injection
Pancreatitis
Pneumothorax
Prolongation of QT interval
Rash
Renal impairment
Rhabdomyolysis
Shortness of breath
Stevens-Johnson syndrome
Syncope
Taste disturbances
Thrombocytopenia
Torsades de pointes
Urinary tract disorders
Vomiting
Wheezing

Presentation

Injectable formulations of pentamidine

Drugs List

Therapeutic Indications

Uses

Leishmaniasis
Pneumocystis jiroveci pneumonia
Prophylaxis of pneumocystis jiroveci pneumonia in HIV patients
Trypanosomiasis

Prophylaxis of Pneumocystis jiroveci pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV) who have had a previous episode of PCP. Administration is by inhalation route.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Administration

For intravenous infusion, deep intramuscular injection or inhalation.

Contraindications

Neonates under 1 month

Precautions and Warnings

Predisposition to pneumothorax
Tobacco smoking
Anaemia
Asthma
Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Hepatic impairment
History of ventricular arrhythmias
Hyperglycaemia
Hypertension
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hypotension
Ischaemic heart disease
Leucopenia
Pregnancy
Renal impairment
Thrombocytopenia

Advise patient dizziness may affect ability to drive or operate machinery
Keep patient supine when receiving injection
Staff: Not to be handled by pregnant staff
Monitor blood pressure before starting treatment
Monitor serum electrolytes before and during treatment
Perform liver function tests before commencing therapy and during therapy
If QTc >550msec during therapy, consider alternative regimen
If QTc>500msec during therapy, continuous cardiac monitoring is required
Monitor blood and platelet counts daily during therapy
Monitor blood pressure
Monitor blood urea nitrogen and serum creatinine daily
Monitor cardiac function by ECG
Monitor fasting blood glucose daily, and regularly after therapy completion
Monitor serum calcium weekly
Monitor serum magnesium twice weekly
Perform urine analysis daily during treatment

Take baseline measurements of liver function tests (LFTs), including bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alkaline aminotransferase (ALT). Test weekly if baseline measurements are normal.
If there is baseline elevation of LFTs or LFTs increase during therapy, continue to monitor weekly unless the patient is receiving concurrent hepatotoxic drugs, when monitoring every 3 - 5 days is appropriate.

Hyperglycaemia with or without preceding hypoglycaemia have occurred up to several months after cessation of therapy. Monitor fasting blood glucose daily during therapy and at regular intervals after cessation of therapy.

The use of aerosolised therapy in patients at high risk of a pneumothorax should be weighed against the clinical consequences of such a manifestation.

Bronchospasm has been reported following nebulised administration. Patients with a history of smoking or asthma seem to be at greater risk. Prior use of bronchodilators can help to control this effect.

Pregnancy and Lactation

Pregnancy

Pentamidine isetionate should not be used during pregnancy unless considered essential. Safety of use during pregnancy has not been established.

A miscarriage during the first trimester has been reported while using aerosolised pentamidine for prophylactic use.

Bystanders, including medical personnel, women of child bearing potential and pregnant women should avoid atmospheric exposure to pentamidine from nebuliser usage.

Animal studies conducted with rats using human equivalent doses showed embryotoxicity but no teratogenic effects. These doses were embryocidal when administered during embryogenesis. Significant placental transfer was observed in rats administered pentamidine in late pregnancy.

Schaefer (2007) concludes that pentamidine should only be administered to pregnant women in cases of life threatening infections when other antibiotics have been ineffective. Inadvertent use does not warrant the termination of pregnancy or the employment of invasive prenatal diagnostic procedures.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pentamidine isetionate should not be used during breastfeeding unless considered essential.

There are no reports available on the use of pentamidine during breastfeeding via any route. The levels of pentamidine in breast milk after administration via nebulisation are probably nil.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abnormal liver function tests
Abscess formation (injection site)
Acute renal failure
Anaemia
Arrhythmias
Azotaemia
Bronchospasm (on inhalation)
Cough
Decreased appetite
Dizziness
Eosinophilic pneumonia
Fatigue
Fever
Flushing
Hyperglycaemia
Hyperkalaemia
Hypocalcaemia
Hypoglycaemia
Hypomagnesaemia
Hypotension
Induration (injection site)
Leucopenia
Light-headedness
Macroscopic haematuria
Nausea
Necrosis (injection site)
Pain on injection
Pancreatitis
Pneumothorax
Prolongation of QT interval
Rash
Renal impairment
Rhabdomyolysis
Shortness of breath
Stevens-Johnson syndrome
Syncope
Taste disturbances
Thrombocytopenia
Torsades de pointes
Urinary tract disorders
Vomiting
Wheezing

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: February 2013

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Pentacarinat 300mg. Sanofi-aventis. Revised March 2012.