PENTACARINAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENTACARINAT (PENTACARINAT).
Pentamidine is an antiprotozoal agent that interferes with the synthesis of nucleic acids and proteins, possibly through inhibition of dihydrofolate reductase and disruption of polyamine synthesis.
| Metabolism | Pentamidine is not extensively metabolized; hepatic metabolism is minimal. Renal excretion is the primary route of elimination. |
| Excretion | Renal: 10-20% unchanged; biliary/fecal: minimal; remainder metabolized. |
| Half-life | Terminal elimination half-life is 3-4 hours in patients with normal renal function, but can be prolonged to 18-24 hours in renal impairment. |
| Protein binding | 80-85% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 0.5 L/kg, indicating distribution into total body water; higher in interstitial edema. |
| Bioavailability | IV: 100%; IM: 60-70%; inhalation: <10% systemic bioavailability due to local deposition. |
| Onset of Action | IV: within 30 minutes; IM: 1-2 hours; inhalation: immediate local effect with systemic absorption delayed. |
| Duration of Action | IV: 4-6 hours; IM: 6-8 hours; inhalation: local effect lasts 6-8 hours; clinical note: duration is dose-dependent. |
4 mg/kg IV once daily for 21 days for Pneumocystis jirovecii pneumonia (PCP) treatment; 300 mg (or 4 mg/kg) via nebulizer once monthly for PCP prophylaxis.
| Dosage form | INJECTABLE |
| Renal impairment | Pentamidine is primarily renally excreted. For CrCl 10-50 mL/min: administer 4 mg/kg IV every 36 hours; for CrCl <10 mL/min: administer 4 mg/kg IV every 48 hours. Monitor closely for nephrotoxicity. |
| Liver impairment | No specific dose adjustment guidelines for hepatic impairment; use with caution and monitor liver function. |
| Pediatric use | PCP treatment: 4 mg/kg IV once daily for 21 days. PCP prophylaxis: 300 mg via nebulizer once monthly (age >=5 years) or 4 mg/kg IV once monthly (if unable to tolerate inhaled). |
| Geriatric use | Use with caution due to age-related renal decline; consider renal dose adjustment and monitor for hypotension, nephrotoxicity, and hypoglycemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENTACARINAT (PENTACARINAT).
| Breastfeeding | It is not known whether pentamidine is excreted in human breast milk. The M/P ratio is unknown. Due to potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Pentamidine isethionate (PENTACARINAT) is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity in rats and rabbits at doses similar to human therapeutic doses. No adequate and well-controlled studies in pregnant women. First trimester: potential for fetal harm based on animal data; use only if clearly needed. Second and third trimesters: no specific malformation patterns reported, but risk of maternal toxicity and potential fetal effects. Consider risk-benefit. |
■ FDA Black Box Warning
WARNING: Pentamidine isethionate injection can cause severe hypotension, hypoglycemia, hyperglycemia, cardiac arrhythmias, and pancreatitis. Fatalities due to severe hypotension and cardiac arrhythmias have been reported. Use only when other therapies are not available.
| Serious Effects |
Hypersensitivity to pentamidine; concurrent use with drugs that prolong QT interval; patients with prolonged QTc interval (e.g., >500 msec) unless benefit outweighs risk.
| Precautions | Risk of severe hypotension, hypoglycemia, hyperglycemia, pancreatitis, QT prolongation, torsades de pointes, nephrotoxicity, hepatotoxicity, and leukopenia. Monitor blood glucose, renal function, liver function, and ECG during therapy. |
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| Fetal Monitoring | Monitor maternal renal function, hepatic function, blood glucose (risk of hypoglycemia or hyperglycemia), and electrolytes (especially calcium and magnesium) due to potential toxicity. Fetal monitoring: consider ultrasound for growth and amniotic fluid volume if prolonged therapy. Monitor for signs of maternal hypotension, arrhythmias, or Stevens-Johnson syndrome. |
| Fertility Effects | No human data on fertility effects. In animal studies, pentamidine did not impair fertility in rats at doses up to 4 times the human dose. However, potential for reproductive toxicity based on testicular alterations in some animal species (rats, dogs) at high doses. Human relevance unknown. |