PENTAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENTAM (PENTAM).
Pentamidine is an antiprotozoal agent that interferes with nucleotide and nucleic acid synthesis, possibly by binding to DNA and inhibiting RNA and protein synthesis. It also affects membrane integrity and inhibits oxidative phosphorylation.
| Metabolism | Pentamidine is metabolized in the liver via cytochrome P450 enzymes, primarily CYP3A4, and undergoes some renal excretion. |
| Excretion | Renal: approximately 60-70% unchanged; biliary/fecal: minimal, <10%. |
| Half-life | Terminal elimination half-life: 6-24 hours (prolonged in renal impairment; up to 48 hours in anuria). |
| Protein binding | 69% (primarily to alpha-1-acid glycoprotein and albumin). |
| Volume of Distribution | Distribution volume: 3-8 L/kg (large, indicating extensive tissue binding, especially to lungs, liver, and kidneys). |
| Bioavailability | Inhalation: <5% systemic absorption; IM: 100%; IV: 100%. |
| Onset of Action | Inhalation: 1-2 weeks for prophylaxis; IV/IM: within 1-2 days for pneumocystosis. |
| Duration of Action | 4-6 weeks after single dose for pentamidine isethionate; weekly or monthly for prophylaxis. |
4 mg/kg intravenously once daily for 21 days (Pneumocystis jirovecii pneumonia); or 300 mg deep intramuscularly every 3 weeks for prophylaxis.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl <10 mL/min: 4 mg/kg IV every 48 hours; avoid IM use. CrCl 10-50 mL/min: 4 mg/kg IV every 24 hours. No adjustment for CrCl >50 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: reduce dose by 25-50% or prolong interval; specific data limited, use with caution. |
| Pediatric use | For PCP treatment: 4 mg/kg IV once daily for 21 days; for prophylaxis: 4 mg/kg IV every 3-4 weeks or 300 mg IM monthly (weight >50 kg use adult dose). |
| Geriatric use | Start at lower end of dosing range due to age-related renal function decline; monitor renal and hepatic function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENTAM (PENTAM).
| Breastfeeding | Pentamidine is excreted into human breast milk in small amounts. The milk-to-plasma ratio (M/P) is not well defined but estimated to be low based on limited data. Due to potential for adverse effects in the nursing infant (e.g., hypoglycemia, nephrotoxicity), caution is advised. The manufacturer recommends avoiding breastfeeding during therapy, especially with intravenous administration. Risk should be weighed against benefits of treatment. |
| Teratogenic Risk | PENTAM (pentamidine) is classified as FDA Pregnancy Category C. Animal studies have demonstrated embryotoxicity and teratogenicity at doses similar to human exposures. There are no adequate and well-controlled studies in pregnant women. First trimester exposure may carry increased risk of congenital anomalies, though specific human data are limited. Second and third trimester use has been associated with maternal and fetal hypoglycemia, hyperglycemia, and hypotension. Late pregnancy exposure may increase risk of neonatal hypoglycemia if maternal blood glucose levels are affected. |
■ FDA Black Box Warning
WARNING: PENTAMIDINE ISETHIONATE FOR INJECTION SHOULD BE USED ONLY IN HOSPITALS WHERE THE PATIENT CAN BE CLOSELY MONITORED FOR SEVERE HYPOTENSION, HYPOGLYCEMIA, AND CARDIAC ARRHYTHMIAS. INTRAMUSCULAR INJECTION HAS BEEN ASSOCIATED WITH STERILE ABSCESS FORMATION.
| Serious Effects |
["History of severe hypersensitivity reaction to pentamidine","Severe hepatic or renal impairment (relative contraindication)","Pre-existing QT prolongation or concurrent use of drugs that prolong QT interval","Pregnancy (use only if clearly needed due to risk of fetal harm)"]
| Precautions | ["Risk of severe hypotension, especially after rapid IV administration","Risk of hypoglycemia or hyperglycemia","Risk of cardiac arrhythmias, including torsades de pointes (QT prolongation)","Pancreatitis","Renal toxicity","Hepatic toxicity","Electrolyte disturbances (hypocalcemia, hypomagnesemia)","Leukopenia and thrombocytopenia","Severe cutaneous reactions (Stevens-Johnson syndrome)"] |
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| Fetal Monitoring | Maternal monitoring: Blood glucose levels (every 6-12 hours during therapy), serum creatinine and BUN, liver function tests, complete blood count, ECG for QT prolongation, blood pressure and heart rate. Fetal monitoring: Ultrasound for growth and development if exposure occurs in first trimester; fetal heart rate monitoring during severe maternal hypotension or hypoglycemia. Newborn monitoring: Blood glucose levels for 24-48 hours after delivery if mother received pentamidine near term. |
| Fertility Effects | Pentamidine has been associated with reversible infertility in animal studies, likely due to testicular toxicity. In humans, male patients may experience oligospermia or azoospermia during therapy, which is typically reversible upon discontinuation. Female fertility: Potential ovarian toxicity with menstrual irregularities has been reported, but data are limited. Impact on fertility in both sexes should be discussed with patients of reproductive age. |