PENTAMIDINE ISETHIONATE inhalant

Krajina: Spojené štáty

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktívna zložka:

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

Dostupné z:

XGen Pharmaceuticals DJB, Inc.

Spôsob podávania:

RESPIRATORY (INHALATION)

Typ predpisu:

PRESCRIPTION DRUG

Terapeutické indikácie:

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/mm 3 . 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 sometime 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.

Prehľad produktov:

Pentamidine Isethionate 300 mg lyophilized product is supplied as: Single-dose glass vial (NDC 39822-3030-01), individually packaged as 1 vial per carton (NDC 39822-3030-02) 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. Manufactured for: XGen Pharmaceuticals DJB, Inc. Big Flats, NY 14814 Rx only Revised: September 2022 PENH-PI-05 PC5142A

Stav Autorizácia:

Abbreviated New Drug Application

Súhrn charakteristických

PENTAMIDINE ISETHIONATE- PENTAMIDINE ISETHIONATE INHALANT
XGEN PHARMACEUTICALS DJB, INC.
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PENTAMIDINE ISETHIONATE FOR INHALATION, 300MG/VIAL
FOR ORAL INHALATION ONLY
DESCRIPTION
Pentamidine Isethionate for inhalation, 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.
C
H
N
O
•2C
H
O
S 592.68
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_
Pentamindine isethionate, an aromatic diamidine, is know 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
®
19
24
4
2
2
6
4
®
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