pentamidine

Action and Spectrum

Actions and Spectrum:

pentamidine is a medication used to treat various infections, including pneumonia caused by the fungus Pneumocystis jiroveci (formerly known as Pneumocystis carinii), which can be a severe complication in people with weakened immune systems.

The action of pentamidine is to inhibit the replication of microorganisms by interfering with their DNA and RNA synthesis. Specifically, it binds to the nucleic acids of the microorganisms, disrupting their replication process and ultimately killing them.

The spectrum of activity of pentamidine is relatively narrow, as it is primarily effective against certain types of bacteria and fungi. In addition to Pneumocystis jiroveci, it can also treat infections caused by certain strains of Trypanosoma brucei (the parasite that causes African sleeping sickness) and Leishmania species (the parasites that cause leishmaniasis).

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Injection 

Leukopenia (10.3%) 

IM site reactions (11%) 

Increased SCr (23%) 

Nebulizer 

Wheezing (32%) 

Fatigue (66%) 

Infection (15%) 

Decreased appetite (50%) 

Cough (1-63%) 

Bronchospasm (48%) 

Fever (51%) 

1-10% 

Injection 

Confusion/hallucinations 

Elevated LFT’s 

Azotemia 

Hypoglycemia 

Thrombocytopenia 

BUN increased 

Anemia 

Hypotension 

Rash 

Anorexia/Nausea/Vomiting 

Fever 

Nebulizer 

Oral Candida 

Night sweats 

Nausea 

Upper respiratory tract infection 

Pharyngitis 

Bitter/metallic taste 

Anemia 

Headache 

Diarrhea 

<1% 

Arthralgia 

Neutropenia 

Anxiety 

Bronchitis 

Chest tightness 

Pleuritis 

Blurred vision 

Blepharitis 

Anemia 

Rales 

Dizziness 

Neuralgia 

Thrombocytopenia 

Colitis

Black Box Warning

Black Box Warning: 

The black box warning for pentamidine highlights the risk of severe hypoglycemia (low blood sugar levels) and insulin-dependent diabetes mellitus, which can occur during treatment and even months to years after discontinuing the medication. It also warns about the potential for severe and fatal cardiac arrhythmias (abnormal heart rhythms) and respiratory arrest (sudden cessation of breathing).

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

pentamidine is contraindicated (should not be used) in individuals with a history of hypersensitivity or severe allergic reactions to pentamidine or its components. Additionally, it should not be used in patients with severe renal impairment or those with a history of hypoglycemia or insulin-dependent diabetes mellitus. 

Other contraindications include pregnancy, breastfeeding, and use in children under 12 unless the potential benefits outweigh the risks. 

pentamidine should also not be used concomitantly with other drugs that can cause QT interval prolongation, as this can increase the risk of cardiac arrhythmias. Drugs that can cause QT interval prolongation include certain antibiotics, antipsychotics, and antiarrhythmics. 

Finally, because pentamidine can cause hypoglycemia, it should not be used in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic disorder affecting the body’s metabolizing glucose. 

It is key to note that this is not a comprehensive list of contraindications for pentamidine. Patients should always consult their healthcare provider before taking any medication and inform them of any pre-existing medical conditions or medications they are currently taking. 

Caution 

Several cautions should be taken into consideration when prescribing pentamidine. These include: 

• Cardiac abnormalities: pentamidine can cause QT interval prolongation and other cardiac abnormalities, particularly in patients with pre-existing cardiac conditions. Patients should be monitored for signs of cardiac arrhythmias and other cardiac side effects. 
• Renal impairment: pentamidine is eliminated from the body primarily through the kidneys. Patients with renal impairment may be at an increased risk of adverse effects from pentamidine, and dosing may need to be adjusted accordingly. 
• Liver impairment: pentamidine can cause liver damage and is contraindicated in patients with severe liver disease. Patients with mild to moderate liver impairment should be closely monitored for signs of liver damage. 
• Respiratory impairment: pentamidine can cause respiratory depression and should be used cautiously in patients with respiratory impairment, such as those with chronic obstructive pulmonary disease (COPD). 
• Hypoglycemia: pentamidine can cause severe hypoglycemia, particularly in patients with pre-existing insulin-dependent diabetes mellitus. Patients should be monitored for signs, symptoms of hypoglycemia, and blood sugar levels should be checked regularly. 
• Concomitant use with other drugs: pentamidine should not be used concomitantly with other drugs that can cause QT interval prolongation or hypoglycemia, as this can increase the risk of adverse effects. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: C 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

pentamidine is a synthetic antimicrobial agent in the class of drugs known as antiprotozoals. It works by disrupting the normal function of the protozoan cell membrane and interfering with DNA and RNA synthesis, ultimately leading to cell death. 

pentamidine is active against various protozoan parasites, including Pneumocystis jiroveci, the protozoan that causes PJP. It also has some activity against certain fungi and bacteria. 

One of the notable pharmacological effects of pentamidine is its ability to cause hypoglycemia, which can be severe and life-threatening in some cases. The drug also has several other potential side effects, including cardiac arrhythmias, renal toxicity, and pancreatitis. Due to these potential side effects, pentamidine is typically used as a second-line treatment for PJP and other infections after other treatments have failed or are not well-tolerated. 

Pharmacodynamics: 

Mechanism of action: The action of this substance involves inhibiting the synthesis of DNA, RNA, phospholipids, and proteins. This is achieved by inhibiting oxidative phosphorylation and interfering with incorporating nucleotides and nucleic acids into RNA and DNA. 

Pharmacokinetics: 

Absorption 

After administration, pentamidine is rapidly absorbed and distributed throughout the body. 

The bioavailability of pentamidine varies depending on the route of administration. When given intravenously, the drug is rapidly and completely absorbed. When given intramuscularly, the bioavailability is lower, with a slower onset of action. The drug is absorbed through the respiratory system when administered via nebulized inhalation. 

Distribution 

pentamidine is highly protein-bound, and body weight and fat distribution affect its distribution throughout the body. 

Metabolism 

pentamidine is primarily metabolized in the liver and excreted in the urine. The drug has a relatively long half-life of around 7 to 10 days, which allows for less frequent dosing. 

Elimination and Excretion 

Approximately 70% of the drug is eliminated within 24 hours of administration, with the majority excreted in the urine. 

Adminstartion

Administration: 

Intravenous or intramuscular administration 

pentamidine can be administered through various routes, including intravenous (IV), intramuscular (IM), and nebulized inhalation. 

The specific administration method and dosing of pentamidine will depend on the patient’s condition, age, weight, and other factors. The medication is typically administered in a healthcare setting, such as a hospital or clinic, under the close supervision of a healthcare professional. 

Intravenous (IV) administration is the most common method for treating Pneumocystis jiroveci pneumonia and other systemic infections. The medication is typically given as a slow infusion over one to two hours, with the dose and frequency based on the patient’s weight and kidney function. 

Intramuscular (IM) administration may sometimes be used, although it is less common than IV administration. When administered IM, the medication is typically given once daily, with the dose based on the patient’s weight. 

Nebulized inhalation is a method of administration that may be used in some instances of Pneumocystis jiroveci pneumonia or other respiratory infections. This method involves using a nebulizer to turn the medication into a mist inhaled through a face mask or mouthpiece. The dose and frequency of nebulized pentamidine will depend on the patient’s age, weight, and other factors. 

It is important to note that pentamidine can have significant side effects, and patients should be closely monitored for signs of adverse reactions during and after treatment. Monitoring kidney function, blood sugar levels, and cardiac function may also be necessary. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pentamidine 

Pronounced: [ pen-TAM-e-deen ] 

Why do we use pentamidine? 

pentamidine is primarily used to treat Pneumocystis jiroveci pneumonia (PJP), a severe lung infection that can occur in people with weakened immune systems, such as those with HIV/AIDS. It is also sometimes used to treat other types of infections caused by protozoan parasites, such as leishmaniasis and African trypanosomiasis (sleeping sickness). 

In addition to its antimicrobial properties, pentamidine also has some antifungal activity and may be used to treat certain fungal infections. 

Another potential use of pentamidine is as a treatment for certain types of cancer, such as multiple myeloma and lymphoma. pentamidine has been shown to have anticancer effects in laboratory studies, although more research is needed to determine its effectiveness in humans. 

Finally, pentamidine is also used as a diagnostic tool in specific medical procedures, such as bronchoscopy, to help identify the presence of certain infections or other conditions.