Definitions

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Pentamidine

[pen-tam-i-deen, -din]
Pentamidine isethionate is an antimicrobial medication primarily given for prevention and treatment of Pneumocystis pneumonia (PCP) caused by 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 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-protozoal action is unknown (though it may involve reactions with ubiquitin), 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 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 WHO or 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:

Drug Interactions

The additional or sequential use of other nephrotoxic drugs like aminoglycosides, 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

  • AHFS Database

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