PENTAMIDINE ISETHIONATE inhalant

Страна: Соединенные Штаты

Язык: английский

Источник: NLM (National Library of Medicine)

Активный ингредиент:

PENTAMIDINE ISETHIONATE (UNII: V2P3K60DA2) (PENTAMIDINE - UNII:673LC5J4LQ)

Доступна с:

Seton Pharmaceuticals

Администрация маршрут:

RESPIRATORY (INHALATION)

Тип рецепта:

PRESCRIPTION DRUG

Терапевтические показания :

Pentamidine Isethionate is indicated for the prevention of Pneumocystis jiroveci pneumonia (PJP) in high-risk, HIV-infected patients defined by one or both of the following criteria: i. a history of one or more episodes of PJP ii. a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm3. These indications are based on the results of an 18-month randomized, dose-response trial in high risk HIV-infected patients and on existing epidemiological data from natural history studies. The patient population of the controlled trial consisted of 408 patients, 237 of whom had a history of one or more episodes of PJP. The remaining patients without a history of PJP included 55 patients with Kaposi’s sarcoma and 116 patients with other AIDS diagnoses, ARC or asymptomatic HIV infection. Patients were randomly assigned to receive Pentamidine Isethionate via the Respirgard® II nebulizer at one of the following three doses: 30 mg every two weeks (n=135), 150 mg every two weeks (n=134) or 300 mg every four weeks (n=139). The results of the trial demonstrated a significant protective effect (p<0.01) against PJP with the 300 mg every four week dosage regimen compared to the 30 mg every two week dosage regimen. The 300 mg dose regimen reduced the risk of developing PJP by 50 to 70% compared to the 30 mg regimen. A total of 293 patients (72% of all patients) also received zidovudine at some time during the trial. The analysis of the data demonstrated the efficacy of the 300 mg dose even after adjusting for the effect of zidovudine. The results of the trial further demonstrate that the dose and frequency of dosing are important to the efficacy of Pentamidine Isethionate prophylaxis in that multiple analyses consistently demonstrated a trend toward greater efficacy with 300 mg every four weeks as compared to 150 mg every two weeks. No dose-response was observed for reduction in overall mortality; however, mortality from PJP was low in all three dosage groups. Pentamidine Isethionate is contraindicated in patients with a history of an anaphylactic reaction to inhaled or parenteral pentamidine isethionate.

Обзор продуктов:

Store dry product at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] Protect the dry product and the reconstituted solution from light.

Статус Авторизация:

Abbreviated New Drug Application

Характеристики продукта

PENTAMIDINE ISETHIONATE- PENTAMIDINE ISETHIONATE INHALANT
SETON PHARMACEUTICALS
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PENTAMIDINE ISETHIONATE FOR ORAL INHALATION ONLY
DESCRIPTION
Pentamidine Isethionate, an antifungal agent, is a nonpyrogenic
lyophilized product.
After reconstitution with Sterile Water for Injection, USP,
Pentamidine Isethionate is
administered by inhalation via the Respirgard® II nebulizer
[Marquest, Englewood, CO]
(see DOSAGE AND ADMINISTRATION). Pentamidine isethionate,
4,4’-[1,5-pentane-
diylbis(oxy)]bis-benzenecarboximidamid, is a white crystalline powder
soluble in water
and glycerin and insoluble in ether, acetone, and chloroform.
Each vial contains 300 mg pentamidine isethionate.
CLINICAL PHARMACOLOGY
_MICROBIOLOGY_
Mechanism of Action
Studies suggest that the pentamidine isethionate interferes with
microbial nuclear
metabolism by inhibition of DNA, RNA, phospholipid and protein
synthesis. However, the
mode of action is not fully understood.
ACTIVITY IN VITRO AND IN VIVO
Pentamidine isethionate, an aromatic diamidine, is known to have
activity against
Pneumocystis jiroveci.
Pharmacokinetics
In 5 AIDS patients with suspected Pneumocystis jiroveci pneumonia
(PJP), the mean
concentrations of pentamidine determined 18 to 24 hours after
inhalation therapy were
23.2 ng/mL (range 5.1 to 43.0 ng/mL) in bronchoalveolar lavage fluid
and 705 ng/mL
(range 140 to 1336 ng/mL) in sediment after administration of a 300 mg
single dose via
the Respirgard® II nebulizer. In 3 AIDS patients with suspected PJP,
the mean
concentrations of pentamidine determined 18 to 24 hours after a 4
mg/kg intravenous
dose were 2.6 ng/mL (range 1.5 to 4.0 ng/mL) in bronchoalveolar lavage
fluid and 9.3
ng/mL (range 6.9 to 12.8 ng/mL) in sediment. In the patients who
received aerosolized
pentamidine, the peak plasma levels of pentamidine were at or below
the lower limit of
detection of the assay (2.3 ng/mL).
Following a single 2-hour intravenous infusion of 4 mg/kg of
pentamidine isethionate to 6
AIDS patients, the mean plasma Cmax, T 1/2 and clearan