Pentamidine 162874 216628281 2008-06-02T14:25:44Z ChemNerd 2246483 Quick-adding category "Amidines" (using [[WP:HOTCAT|HotCat]]) {{drugbox | IUPAC_name = 4-[5-(4-carbamimidoylphenoxy) pentoxy]benzenecarboximidamide | image = Pentamidine-2D-skeletal.png | CAS_number = 100-33-4 | ATC_prefix = P01 | ATC_suffix = CX01 | ATC_supplemental = | PubChem = 4735 | DrugBank = APRD00303 | C=19 | H=24 | N=4 | O=2 | molecular_weight = 340.42 g/mol | bioavailability = | protein_bound = 69% | metabolism = | elimination_half-life = 6.4-9.4 hours | pregnancy_US = C | legal_status = | routes_of_administration = [[Intravenous therapy|IV]], [[Intramuscular|IM]], inhalation }} '''Pentamidine isethionate''' is an [[antimicrobial]] [[medication]] primarily given for prevention and treatment of [[Pneumocystis pneumonia]] (PCP) caused by [[Pneumocystis pneumonia|''Pneumocystis jirovecii'']], also formerly known as ''Pneumocystis carinii pneumonia'' (PCP), a severe interstitial type of [[pneumonia]] often seen in patients with [[HIV]] infection. PCP is considered an '[[opportunistic infection]]', endangering only [[immunodeficiency|immunodeficient]] patients such as those with HIV/AIDS. ==Uses== Pentamidine is also used as a prophylactic in patients receiving chemotherapy, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating [[Leishmaniasis]], [[sleeping sickness]] caused by different strains of [[Trypanosoma]], and yeast infections caused by the organism ''[[Candida albicans]]''. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia. The exact mechanism of its anti-[[protozoa]]l action is unknown (though it may involve reactions with [[ubiquitin]]<ref name="pmid17191940">{{cite journal |author=Nguewa PA, Fuertes MA, Cepeda V, ''et al'' |title=Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin |journal=Chem. Biodivers. |volume=2 |issue=10 |pages=1387–400 |year=2005 |pmid=17191940 |doi=10.1002/cbdv.200590111}}</ref>), despite the fact that it's a basic therapeutic modality (in concurrence with multiple antifungal medications) when treating Acanthamoeba infections in the immunocompromised patients. The drug has also activity against (missing microbe) in clinically relevant concentrations. In the [[United States]], pentamidine is currently designated an [[orphan drug]] by the [[FDA]]. ===Treatment of acute PCP=== In the acute treatment of PCP, pentamidine is considered equally or slightly less active than [[co-trimoxazole]] (brand names Bactrim, Septrin, or Septra). Clinical evidence suggests that pentamidine is often better tolerated than co-trimoxazole because a high dose of co-trimoxazole is needed, which is associated with a high incidence and severity of side effects such as hepatitis, bone-marrow-damage, renal-damage, and life threatening skin disease (Lyell-syndrome). Moreover, many patients are or become [[allergy|allergic]] to co-trimoxazole. For treatment of PCP, 4 milligrams of pentamidine per kilogram of body weight is given intravenously once daily for 14 to 21 days. Treatment exceeding 21 days may be necessary, but is associated with increased toxicity. [[Intramuscular injection]] is not recommended. The effect of pentamidine often becomes evident within the first 2 days of treatment, with reduction in fever and improvement of respiratory function. In any case, improvements of [[chest x-ray]] studies occur within 6 to 8 days, provided therapy is successful. Pentamidine therapy cures 50 to 70% of all patients treated. ===Primary and Secondary Prophylaxis of PCP=== Primary prophylaxis of severely immunocompromised patients can be indicated where PCP has not yet been diagnosed. Secondary prophylaxis aims to prevent recurrent infections by PCP. For both forms of prophylaxis, an aerosolized formulation of pentamidine given by nebulizer once monthly in a dose of 300mg is used. In primary prophylaxis, this reduces the long term likelihood of PCP by 70% when compared to no prophylaxis. ===Other infections=== For other indications, such as leishmaniasis or sleeping sickness, special treatment schedules developed by the [[World Health Organization|WHO]] or [[Centers for Disease Control|CDC]] exist. ==Contraindications== * Severe allergy; no others in PCP patients in whom a proper diagnosis has been made ==Side effects== Pentamidine can cause allergic and toxic side effects, which in part depend on the daily and/or cumulative dose: * [[Kidney]] : 25 percent develop signs of [[nephrotoxicity]] ranging from mild, asymptomatic [[azotemia]] (increased serum [[creatinine]] and [[urea]]) to irreversible [[renal failure]]. Ample fluids or intravenous hydration may prevent some nephrotoxicity. * [[Cardiovascular system|Cardiovascular]] : [[Hypotension]], which may be severe, severe or fatal [[arrhythmia]]s and [[heart failure]] are quite frequent. * [[Digestive system|Gastrointestinal]] : [[Nausea]], vomiting, gastrointestinal discomfort, [[diarrhea]], unpleasant taste * [[Pancreas]] : [[Hypoglycemia]] that requires symptomatic treatment is frequently seen. On the other hand, pentamidine may cause or worsen [[diabetes mellitus]]. * [[Liver]] : Elevated [[liver enzymes]] are associated with intravenous use of pentamidine. [[Hepatomegaly]] and [[hepatitis]] have been encountered with long term prophylactic use of pentamidine inhalation. * [[Skin]] : Severe local reactions after extravasculation of intravenous solutions or following intramuscular injection treatment have been seen. Pentamidine itself may cause rash, or rarely [[Stevens-Johnson syndrome]] or Lyell syndrome. * [[Blood]] : Pentamidine frequently causes [[leukopenia]] and less often [[thrombopenia]], which may cause symptomatic bleeding. Some cases of [[anemia]], possibly related to [[folic acid]] deficiency, have been described. * [[Nervous system|Neurological]] : Dizziness, drowsiness, [[neuralgia]], confusion, hallucinations, [[seizure]]s and other central side effects are reported. * [[Respiratory system|Respiratory]] : Cough and [[bronchospasm]], most frequently seen with inhalation. * Others : Eye discomfort, [[conjunctivitis]], throat irritation, [[splenomegaly]], [[Herxheimer reaction]], [[electrolyte]] imbalances (e.g. [[hypocalcemia]]). ==Drug Interactions== The additional or sequential use of other nephrotoxic drugs like [[aminoglycoside]]s, [[amphotericin B]], [[capreomycin]], [[colistin]], [[polymyxin B]], [[vancomycin]], [[foscarnet]], or [[cisplatin]] should be closely monitored, or whenever possible completely avoided. ==Brand Names and Dose Forms== * For oral inhalation : NebuPent 300mg Nebulizer * For parenteral treatment : Pentacrinat, Pentam 300, and Pentamidine isethionate for injection (Abbot); all containing 300mg of Pentamidine ==External references== <references/> * AHFS Database {{Agents against leishmaniasis and trypanosomiasis}} [[Category:Antifungals]] [[Category:Antiprotozoal agents]] [[Category:Amidines]] [[de:Pentamidin]] [[fr:Pentamidine]]