Pentamidine (NebuPent, Pentam): Uses, Dosing, and Risks

Q: What is pentamidine used for?

Mainly to prevent PCP (inhaled NebuPent) and to treat PCP (injected Pentam) in people with weakened immune systems. It is also used off-label for some parasitic infections such as leishmaniasis and sleeping sickness.

Q: What is the difference between NebuPent and Pentam?

NebuPent is inhaled once every four weeks to prevent PCP in high-risk people with HIV. Pentam 300 is an injection or infusion given daily for 14 to 21 days to treat active PCP.

Q: How often is NebuPent given?

300 mg once every 4 weeks by nebulizer, over about 30 to 45 minutes.

Q: What are the side effects of inhaled pentamidine?

Mainly cough and bronchospasm. A bronchodilator is usually given first. People with asthma or a smoking history are more prone to these effects.

Q: What are the serious risks of injected pentamidine?

The label reports fatalities due to severe low blood pressure, low blood sugar, acute pancreatitis, and heart rhythm problems. Kidney damage is common, and blood and liver effects occur, so close monitoring is required.

Q: Why must patients lie down for pentamidine injections?

Severe low blood pressure can occur suddenly after a single dose. The label says patients should be lying down and monitored closely during and after administration.

Q: Can pentamidine affect blood sugar?

Yes. It can cause low blood sugar, and high blood sugar and diabetes have also occurred, sometimes months after treatment. Glucose is monitored daily during therapy and afterward.

Q: Is pentamidine safe in pregnancy?

It is Pregnancy Category C, so it should be given only if the benefit outweighs the unknown risks. Discuss with your doctor.

Q: Is pentamidine the first choice for PCP?

Usually other medicines are considered first when they can be taken, and pentamidine is an important alternative. Your doctor decides based on your situation.

Pentamidine is an antimicrobial medicine used mainly to prevent and treat Pneumocystis pneumonia (PCP), a serious lung infection that affects people with weakened immune systems, especially those with advanced HIV. It comes in two very different forms. NebuPent is an inhaled version, breathed in through a nebulizer once every four weeks to prevent PCP. Pentam 300 is an injection, given into a vein or muscle to treat an active PCP infection, and it carries some of the more serious warnings you will find on any antimicrobial label.

This guide explains what pentamidine is, how it works, the difference between the inhaled and injected forms, how each is dosed, the side effects and monitoring, who should be careful, other uses such as leishmaniasis and sleeping sickness, and what to ask your care team. It replaces our separate page on NebuPent.

This is general information based on FDA labeling and NIH guidance, not medical advice. Pentamidine is given under close medical supervision. Only your care team can decide whether it is right for you.

Table of Contents

Pentamidine at a glance

	NebuPent (inhaled)	Pentam 300 (injection)
FDA-approved use	Prevention of PCP in high-risk HIV-infected patients	Treatment of PCP (Pneumocystis pneumonia)
Route	Inhaled with a Respirgard II nebulizer	Deep intramuscular injection or intravenous infusion
Typical schedule	300 mg once every 4 weeks	4 mg/kg once a day for 14 to 21 days
Who gets it	People with a past PCP episode or CD4 count of 200 or less	People with PCP confirmed
Main safety issues	Cough, bronchospasm	Low blood pressure, low or high blood sugar, kidney damage, pancreatitis, heart rhythm problems
Setting	Clinic or hospital	Clinic or hospital, patient lying down

What PCP is and why it matters

Pneumocystis jirovecii is a fungus that most people encounter without becoming ill. In someone with a severely weakened immune system, it can cause pneumonia. The NIH describes PCP as an opportunistic infection (OI) of HIV, meaning an infection that occurs more frequently or more severely in people with weakened immune systems than in people with healthy ones. It is a leading serious infection in people with advanced HIV who are not on effective treatment, and it can also affect people whose immune systems are suppressed by other conditions or medicines.

Preventing PCP in people at risk, and treating it promptly if it develops, has saved many lives. Modern HIV treatment, which restores immune function, has made PCP much less common, but it still occurs.

How pentamidine works

Pentamidine belongs to a chemical family called aromatic diamidines. The label states that the mode of action is not fully understood. Laboratory studies indicate that the drug interferes with the nuclear metabolism of the organism by inhibiting the synthesis of DNA, RNA, phospholipids, and proteins.

Although it is called an antifungal in some drug databases, and an antiprotozoal in its label, the organism it targets (Pneumocystis) has features of both, which is why classifications differ. What matters clinically is that it is active against Pneumocystis and against certain protozoal parasites.

NebuPent: inhaled pentamidine to prevent PCP

Who it is for

NebuPent is indicated for the prevention of Pneumocystis jirovecii pneumonia in high-risk, HIV-infected patients, defined by one or both of:

Calendar with one nebulizer treatment every four weeks and a 45 minute clock for NebuPent

A history of one or more episodes of PCP, or
A peripheral CD4+ lymphocyte count of 200 per cubic millimeter or less.

It is not for treating an existing PCP infection, and the label instructs prescribers to exclude PCP before starting prophylaxis.

How it is given

Dose. 300 mg once every 4 weeks in adults.
Device. It is reconstituted and delivered by inhalation with the Respirgard II nebulizer, which is designed for this use.
Time. Roughly 30 to 45 minutes, until the nebulizer chamber is empty.
Age. Not recommended for children 16 and younger, according to prescribing summaries.
Not mixed with other drugs. The vial is not to be mixed with other medicines.

What the trial showed

The approval rests on an 18-month randomized dose-response trial in high-risk HIV-infected patients. Participants were assigned to three inhaled regimens: 30 mg every two weeks (135 patients), 150 mg every two weeks (134 patients), or 300 mg every four weeks (139 patients). The 300 mg every four weeks regimen showed a significant protective effect against PCP compared with 30 mg every two weeks (p<0.01).

Side effects and precautions

Because the drug is inhaled, the concerns are mainly in the airways.

Cough and bronchospasm. Inhaled pentamidine can trigger coughing and wheezing. The label advises giving an inhaled bronchodilator before the NebuPent dose, and warns not to use the Respirgard II nebulizer to give the bronchodilator.
Smoking and asthma. People with a history of smoking or asthma are more prone to bronchospasm and need particular care.
Taste and other effects. A metallic or bad taste, fatigue, shortness of breath, and throat irritation are reported. Report anything that worries you.
Limited whole-body exposure. Because most of the drug stays in the lungs, systemic side effects are much less common than with the injection, though not impossible.
Pregnancy and nursing. It is Pregnancy Category C, and nursing is not recommended, according to prescribing summaries. Discuss it with your doctor.
Infection control. The nebulizer procedure can release droplets, so clinics use precautions and rooms designed to protect other patients and staff.

Pentam 300: injected pentamidine to treat PCP

What it is for

Pentam 300 (pentamidine isethionate for injection) is indicated for the treatment of pneumonia due to Pneumocystis carinii (the older name of the organism). It is given by deep intramuscular (IM) injection or by intravenous (IV) infusion.

Dosing

The recommended regimen for adults and pediatric patients beyond 4 months of age is 4 mg/kg once a day for 14 to 21 days. Treatment for longer than 21 days has been used but may be associated with increased toxicity.

IV administration details from the label:

Dissolve the vial in Sterile Water for Injection or 5% Dextrose Injection, then dilute further in 50 to 250 mL of 5% Dextrose.
Infuse over 60 to 120 minutes. Rapid infusion makes severe low blood pressure more likely.
Do not use sodium chloride injection for initial reconstitution, because a precipitate forms.

IM administration: the vial is dissolved in 3 mL of Sterile Water for Injection and given as a deep intramuscular injection.

Serious warnings

The Pentam label opens its warnings with a stark statement: fatalities due to severe hypotension, hypoglycemia, acute pancreatitis, and cardiac arrhythmias have been reported in patients treated with pentamidine, by both the IM and IV routes.

Severe low blood pressure. It can happen suddenly after a single dose, IV or IM, and is more likely with rapid IV administration. The label says patients receiving the drug should be lying down and that blood pressure should be monitored closely during the infusion and several times afterward until stable, with resuscitation equipment on hand.
Low blood sugar (hypoglycemia). Pentamidine-induced hypoglycemia has been associated with damage to the pancreatic islet cells and inappropriately high insulin levels. Hyperglycemia and diabetes mellitus have also occurred, sometimes several months after therapy, so blood glucose should be monitored daily during therapy and several times afterward.
Pancreatitis. Inflammation of the pancreas can occur and can be severe.
Heart rhythm problems. Arrhythmias have been reported, and torsades de pointes was described in post-marketing experience. Electrocardiograms are part of monitoring. Other medicines that prolong the QT interval add to this risk.
Kidney problems. Nephrotoxic events (increased creatinine, impaired renal function, azotemia, and renal failure) are common with injected pentamidine. In the label’s data, elevated creatinine occurred in 23.6% of patients and impaired renal function in 28.8%.
Blood cell effects. Leukopenia occurred in 10.4%, thrombocytopenia in 2.6%, and anemia in 1.2%.
Extravasation. If the drug leaks outside the vein, it can cause ulceration, tissue death, and sloughing, sometimes requiring surgical debridement and skin grafting. The IV site must be watched closely.
Only for confirmed PCP. The label limits use to patients in whom Pneumocystis has been demonstrated, because of the seriousness of these risks.

Other side effects

The most frequently reported adverse events (1 to 30%) in clinical trials were:

Category	Event	Frequency
Kidney	Impaired renal function	28.8%
Kidney	Elevated serum creatinine	23.6%
Skin	Sterile abscess, necrosis, pain, or hardness at the IM injection site	11.1%
Blood	Leukopenia	10.4%
Kidney	Azotemia	8.5%
Liver	Elevated liver function tests	8.7%
Kidney	Elevated blood urea nitrogen	6.6%
Heart	Hypotension	5.0%
Metabolic	Hypoglycemia	5.9%
Stomach	Anorexia or nausea	5.9%
Skin	Rash	3.3%
Blood	Thrombocytopenia	2.6%
Nervous system	Confusion or hallucinations	1.7%
Taste	Bad taste	1.7%

Less common events reported include allergic reactions, anaphylaxis, Stevens-Johnson syndrome, pancreatitis, hepatitis, high potassium, low calcium and magnesium, and neurological symptoms.

Monitoring

The label calls for these tests before, during, and after therapy:

Daily blood urea nitrogen and serum creatinine
Daily blood glucose
Complete blood count and platelet count
Liver function tests (bilirubin, alkaline phosphatase, AST, ALT)
Serum calcium
Electrocardiograms

Drug interactions and special populations

Other kidney-toxic drugs. Because the kidney toxicity may be additive, using pentamidine together with or right after aminoglycosides, amphotericin B, cisplatin, foscarnet, or vancomycin should be closely monitored and avoided if possible.
Drugs affecting blood sugar. Pentamidine can cause low or high blood sugar, so people who take insulin or diabetes medicines may need dose changes and more glucose checks.
QT-prolonging drugs. Combining them raises the risk of dangerous rhythms.
Pregnancy. Pregnancy Category C. It should not be given to a pregnant woman unless the benefit outweighs the unknown risks.
Nursing. It is not known whether it passes into breast milk, and the label advises weighing discontinuing nursing or the drug.
Children. Effective for PCP in immunocompromised pediatric patients beyond 4 months of age, with similar efficacy and safety as in adults.
Overdose. The label describes a 17-month-old infant who accidentally received 1,600 mg intravenously and developed kidney and liver impairment, low blood pressure, and cardiopulmonary arrest, which shows how important precise weight-based dosing is.

When pentamidine is used

Guidelines for people with HIV, including the NIH Guidelines for the Prevention and Treatment of Opportunistic Infections, include recommendations on the use of pentamidine to treat PCP and cutaneous leishmaniasis and to prevent PCP (both the first episode and recurrences) and recurrence of visceral leishmaniasis. The NIH notes that recommended uses may not always match FDA-approved uses.

In practice, other medicines are often used first for PCP prevention and treatment when they can be taken, and pentamidine is an important alternative, such as when other drugs cause allergy or intolerable side effects. Your doctor chooses based on your history, other medicines, and what you can tolerate.

Other uses

Pentamidine is also used, off-label in the United States, for other infections:

Leishmaniasis. According to a drug reference, dosing for visceral leishmaniasis uses 2 to 4 mg/kg intramuscularly every 24 to 48 hours for 15 to 30 doses, and for cutaneous disease 2 mg/kg every other day for 7 doses or 3 mg/kg every other day for 4 doses.
African trypanosomiasis (sleeping sickness). 4 mg/kg intramuscularly daily for 10 days is listed as an off-label regimen. Modern sleeping sickness care also uses other regimens. See our guides to eflornithine and nifurtimox.

These uses are led by infectious disease specialists.

What to tell your provider before pentamidine

The NIH advises telling your healthcare provider if you:

Are allergic to pentamidine or other medicines
Have high or low blood pressure
Have heart rhythm problems
Have diabetes, or high or low blood sugar
Have low calcium
Have had pancreatitis
Have anemia, thrombocytopenia, or leukopenia
Have liver or kidney problems
Have had Stevens-Johnson syndrome
Have asthma or difficulty using a nebulizer
Are pregnant or planning pregnancy, or are breastfeeding

Tips for a smoother experience

For inhaled NebuPent:

Arrive on time for your every-four-weeks appointment, and plan for about an hour.
If you smoke or have asthma, make sure the team knows so a bronchodilator can be given first.
Report cough, wheezing, or shortness of breath right away.
Tell your team about any new respiratory symptoms, fever, or dry cough between visits, since they could be a sign of PCP.

For injected Pentam:

Expect close monitoring: lying down, frequent blood pressure checks, and daily blood tests.
Report dizziness, palpitations, sweating, shakiness, or severe abdominal pain immediately.
Tell staff about pain, swelling, or burning at the IV site.
Keep track of your other medicines and share the list.

Questions to ask your care team

Why is pentamidine the right choice for me, compared with other medicines?
For NebuPent, how will we manage cough or wheezing?
For Pentam, how will you monitor my blood pressure, blood sugar, kidneys, and heart?
What symptoms mean I should call right away or go to the emergency room?
Which of my other medicines interact with it?
What is my plan for staying on prevention as long as I need it?
What effects might show up months later, such as changes in blood sugar?

Frequently asked questions

What is pentamidine used for?