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pentamidine; 4,4' diamidinophenoxy pentane (Pentam 300, Nebupent)

Tradename: Pentam-300. 4,4' diamidinophenoxy pentane. Pentamidine isethionate (Pentam 300, Nebupent) Indications: - treatment of early African trypanosomiasis (ineffective if CNS involved) - leishmaniasis, cutaneous & visceral. - treatment of Pneumocystis pneumonia - prophylaxis for Pneumocystis carinii Dosage: 1) pneumocystis: 4 mg/kg IV/IM QD for 14-21 days 2) trypanisomiasis: 4 mg/kg IV/IM QD for 10 days Nebulized: Tradename NebuPent. - 300 mg nebulized every 4 weeks via Respirgard II nebulizer Aerosol: 300 mg vial Injection: 300 mg vial Dosage adjustment in renal failure: creatinine clearance dosage > 50-90 mL/min every 24 hours 10-50 mL/min every 24 hours < 10 mL/min every 24-36 hours Pharmacokinetics: 1) 1/2life is 6.4-9.4 hours (118 hours ESRD) 2) 33-66% of drug is eliminated unchanged into the urine Caution: Although < 5% of pentamidine is renally excreted, the 1/2life is prolonged in dialysis patients, with a terminal 1/2life after multiple doses as long as 10-15 days. Monitor: - liver function tests (serum AST, serum ALT, serum bilirubin, serum alkaline phosphatase) before, during, & after treatment [9] Adverse effects: 1) common (> 10%) - chest pain, rash, wheezing, dyspnea, coughing, pharyngitis, hyperkalemia, local reaction at site of injection, acute renal failure [2] 2) less common (1-10%) - bitter or metallic taste 3) uncommon (< 1%) - extrapulmonary pneumocystis, pancreatitis, pneumothorax, hyperglycemia, hypoglycemia, renal insufficiency, hypotension, tachycardia, dizziness, fever, Jarisch-Herxheimer-like reaction, hypocalcemia, vomiting, megaloblastic anemia, granulocytopenia, leukopenia, thrombocytopenia, mild renal or hepatic injury, airway irritation, fatigue 4) other [2] a) directly toxic to pancreatic islet cells - hypoglycemia - diabetes b) hyperkalemia - inhibits tubular excretion of K+ c) nebulized pentamidine - chest pain - bronchospasm - cough - bitter taste Drug interactions: - foscarnet in combination increases risk of hypoglycemia & nephrotoxicity Laboratory: 1) specimen: a) serum, plasma; stable at -20 degrees C for 6 days b) whole blood, urine 2) methods: a) serum/plasma: HPLC, bioassay, LSIMS, CZE b) whole blood: HPLC; urine: bioassay, HPLC Mechanism of action: 1) inhibits dihydrofolate reductase 2) interferes with DNA/RNA, phospholipid & protein synthesis 3) complete mechanism of action is unclear

Interactions

drug interactions

General

antiprotozoal agent diamidine

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 6.4-9.4 HOURS 26-32 HOURS 10-15 DAYS therapeutic-range 250 +/- 80 NG/ML pregnancy-category C safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1990, pg 1011-3
  2. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, 1190
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 625
  5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  6. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  7. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  8. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  9. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com