Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as isethionate [preservative free]:
Pentam: 300 mg (1 ea)
Generic: 300 mg (1 ea)
Pharmacology
Mechanism of Action
Interferes with microbial RNA/DNA, phospholipids and protein synthesis, through inhibition of oxidative phosphorylation and/or interference with incorporation of nucleotides and nucleic acids into RNA and DNA
Pharmacokinetics/Pharmacodynamics
Absorption
IM: Well absorbed
Distribution
Binds to tissues and plasma protein; high concentrations are found in the liver, kidney, adrenals, spleen, lungs, and pancreas; poor penetration into CNS; Vdss: IV: 286 to 1356 L; IM: 1658 to 3790 L
Excretion
Urine (IV: ≤12% as unchanged drug)
Half-Life Elimination
IV: 5 to 8 hours; IM: 7 to 11 hours; may be prolonged with severe renal impairment
Use in Specific Populations
Special Populations: Renal Function Impairment
Pentamidine may accumulate in renal failure.
Use: Labeled Indications
Treatment of pneumonia caused by Pneumocystis jirovecii pneumonia (PCP)
Use: Off Label
West African trypanosomiasis (Trypanosoma brucei gambiense infection; sleeping sickness), hemolymphatic stagec
The Centers for Disease Control and Prevention (CDC) suggest pentamidine may be beneficial in treating the hemolymphatic stage of T. b. gambiense infection in individuals with trypanosomiasis CDC 2019.
Contraindications
Hypersensitivity to pentamidine isethionate or any component of the formulation
Dosage and Administration
Dosing: Adult
Pneumocystis jirovecii pneumonia (PCP), treatment (alternative agent): IV: 4 mg/kg/dose once daily (manufacturer's labeling) for 21 days; may reduce to 3 mg/kg/dose once daily if toxicity occurs (HHS [OI adult 2015]).
West African trypanosomiasis (Trypanosoma brucei gambiense infection; sleeping sickness), hemolymphatic stage (off-label use): IM, IV: 4 mg/kg once daily for 7 to 10 days (CDC 2019).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Pneumocystis jirovecii (PCP), prophylaxis (primary and secondary) in oncology patients (including HSCT recipients): Limited data available: Note: For patients intolerant to sulfamethoxazole and trimethoprim. Children ≥2 years and Adolescents: IV: 4 mg/kg/dose once a month (Kim 2008; Prasad 2007); in HSCT recipient doses have been administered every 2 to 4 weeks (Tomblyn [CDC/IDSA 2009])
PCP, treatment (moderate-severe disease): Note: For patients who cannot tolerate or who fail to respond to 5 to 7 days of sulfamethoxazole and trimethoprim.
Manufacturer's labeling: Infants ≥5 months, Children, and Adolescents: IM, IV: 4 mg/kg/dose once daily for 14 to 21 days
HIV-exposed/-positive:
Infants and Children: IV: 4 mg/kg/dose once daily; if clinical improvement after 7 to 10 days of therapy, may change to an oral regimen to complete a 21-day course (DHHS [pediatric] 2013)
Adolescents: IV: 4 mg/kg/dose once daily for 21 days; some experts recommend a dose reduction to 3 mg/kg/dose for toxicity (DHHS [adult] 2015)
Non-HIV-exposed/-positive: Infants, Children, and Adolescents: IV: 3 to 4 mg/kg/dose once daily for 21 days (Bradley 2015)
Trypanosomiasis; treatment (non-CNS disease): Infants, Children, and Adolescents: IM, IV: 4 mg/kg/dose once daily for 7 to 10 days (Bradley 2015; Red Book [AAP 2015])
Reconstitution
Do not use sodium chloride for initial reconstitution (sodium chloride will cause precipitation).
IM: Reconstitute with 3 mL SWFI; IV: Reconstitute with 3 to 5 mL SWFI or D5W; the manufacturer recommends further dilution in 50 to 250 mL D5W; however, stability with further dilution in NS has also been documented.
Administration
Do not use NS to reconstitute.
IM: Administer deep IM
IV: Infuse slowly over 60 to 120 minutes.
Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry warm compresses (Reynolds 2014).
Storage
Store intact vials at 20°C to 25°C (68°F to 77°F); protect from light. Do not use sodium chloride for initial reconstitution (sodium chloride will cause precipitation).
Reconstituted solution is stable for 48 hours in the vial at room temperature and protected from light. Solutions for injection (1 to 2.5 mg/mL) in D5W are stable for at least 24 hours at room temperature. Store at room temperature to avoid crystallization.
Drug Interactions
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
Domperidone: May enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
Fexinidazole [INT]: Pentamidine (Systemic) may enhance the QTc-prolonging effect of Fexinidazole [INT]. Avoid combination
Foscarnet: Pentamidine (Systemic) may enhance the adverse/toxic effect of Foscarnet. The specific toxicities may include hypocalcemia, renal failure, and QT-prolongation. Management: Consider alternatives to this combination when possible. If this combination must be used, monitor patients more closely for hypocalcemia, renal dysfunction, and QT interval prolongation. Consider therapy modification
Haloperidol: May enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Mequitazine: Pentamidine (Systemic) may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to pentamidine or mequitazine when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Ondansetron: Pentamidine (Systemic) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of Pentamidine (Systemic). Avoid combination
Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide. Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Pentamidine (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Saquinavir: Pentamidine (Systemic) may enhance the QTc-prolonging effect of Saquinavir. Avoid combination
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Adverse Reactions
>10%:
Local: Injection site reaction (intramuscular: 11%; includes sterile abscess, necrosis, pain, induration)
Renal: Renal insufficiency (29%), increased serum creatinine (24%)
1% to 10%:
Cardiovascular: Hypotension (5%)
Central nervous system: Confusion (≤2%), hallucinations (≤2%)
Dermatologic: Skin rash (3%)
Endocrine & metabolic: Hypoglycemia (6%)
Gastrointestinal: Anorexia (≤6%), nausea (≤6%), dysgeusia (2%)
Hematologic & oncologic: Leukopenia (10%), thrombocytopenia (3%), anemia (1%)
Hepatic: Increased liver enzymes (9%)
Renal: Azotemia (9%), increased blood urea nitrogen (7%)
<1%, postmarketing, and/or case reports: Abdominal pain, acute pancreatitis, acute rhinitis, ageusia, amnesia, anaphylaxis, anosmia, anxiety, arthralgia, asthma, blepharitis, blurred vision, bronchitis, bronchospasm, cardiac arrhythmia, cerebrovascular accident, chest congestion, chest tightness, chills, confusion, conjunctivitis, contact lens intolerance, cough, cyanosis, depression, dermatitis, desquamation, diabetes mellitus, diabetic ketoacidosis, diarrhea, disseminated intravascular coagulation, dizziness, drowsiness, dry hair, dyspepsia, dyspnea, emotional lability, eosinophilia, eosinophilic pneumonitis, erythema, extravasation (tissue ulceration, necrosis, and/or sloughing), eye pain, flank pain, gag reflex, hair breakage, headache, hearing loss, hematochezia, hematuria, hemoptysis, hepatic insufficiency, hepatitis, hepatomegaly, hyperglycemia, hyperkalemia, hypersensitivity reaction, hypertension, hyperventilation, hypocalcemia, hypoesthesia, hypomagnesemia, insomnia, interstitial pneumonitis, laryngitis, laryngospasm, melena, nasal congestion, nephritis, nervousness, neuralgia, neuropathy, neutropenia, night sweats, palpitations, pancreatitis, pancytopenia, paranoia, paresthesia, peripheral neuropathy, phlebitis, pleurisy, pneumothorax, prolonged prothrombin time, pruritus, pulmonary disease, rales, renal failure, renal insufficiency, rhinitis, seizure, serious infection (extrapulmonary pneumocystosis), sialorrhea, splenomegaly, Stevens-Johnson syndrome, ST segment changes on ECG, syncope, tachycardia, tachypnea, torsades de pointes, tremor, unsteady gait, urinary incontinence, urticaria, vasodilation, vasculitis, ventricular tachycardia, vertigo, vomiting, xeroderma, xerostomia
Warnings/Precautions
Concerns related to adverse effects:
- Hypotension: Severe hypotension (some fatalities) has been observed, even after a single dose. May occur with either IV or IM administration, although more common with rapid IV administration. Monitor blood pressure during (and after) infusion.
- QT prolongation: May cause QT prolongation and subsequent torsade de pointes; avoid use in patients with diagnosed or suspected congenital long QT syndrome.
- Stevens-Johnson syndrome: Has been reported with use.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with preexisting cardiovascular disease; hyper-/hypotension and arrhythmia, including ventricular tachycardia (eg, torsade de pointes) have been reported.
- Diabetes: Use with caution in patients with diabetes mellitus; hyper-/hypoglycemia and pancreatic islet cell necrosis with hyperinsulinemia has been reported. Symptoms may occur months after therapy; monitor blood glucose daily on therapy and periodically thereafter.
- Extravasation: Intravenous pentamidine is an irritant with vesicant-like properties. Ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Ulceration, tissue necrosis, and/or sloughing have been reported with extravasation.
- Hematologic disorders: Use with caution in patients with current evidence and/or prior history of hematologic disorders; anemia, leukopenia and/or thrombocytopenia have been reported. Concurrent use with other bone marrow suppressants may increase the risk for myelotoxicity.
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Hypocalcemia: Use with caution in patients with hypocalcemia.
- Pancreatitis: Use with caution in patients with a history of pancreatic disease or elevated amylase/lipase levels; acute pancreatitis (with fatality) has been reported. Discontinue pentamidine if signs/symptoms of acute pancreatitis occur.
- Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
- Drugs with QT prolongation potential: Avoid concurrent use with other drugs known to prolong QTc interval.
- Nephrotoxic drugs: Concurrent use with other nephrotoxic drugs may increase the risk for nephrotoxicity.
Monitoring Parameters
Liver function tests, renal function tests, blood glucose, serum potassium and calcium, CBC and platelets; ECG, blood pressure
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Pentamidine crosses the human placenta (Fortunato 1989; Schwebke 1995).
Intravenous pentamidine can be used as an alternative treatment in pregnant females with HIV infection for mild to moderate Pneumocystis jirovecii pneumonia (HHS [OI; adult] 2017). Pentamidine may be used to treat stage one trypanosomiasis caused by T. brucei gambiense (CDC 2016); information related to treatment of pregnant females for this indication is limited (Pohlig 2016).
Patient Education
What is this drug used for?
- It is used to treat Pneumocystis jirovecii pneumonia.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Nausea
- Lack of appetite
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
- Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
- High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
- Low calcium like muscle cramps or spasms, numbness and tingling, or seizures.
- Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
- High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.
- Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes.
- Infection
- Abnormal heartbeat
- Severe dizziness
- Passing out
- Bruising
- Bleeding
- Severe loss of strength and energy
- Severe injection site redness, swelling, blisters, burning, pain, or irritation
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
