Aerosolized pentamidine

The patient may be required to receive aerosol pentamidine at home. Before discharge, the nurse checks to make sure that arrangements have been made to deliver the specialized equipment and supplies, such as a Respirgard II nebulizer and diluent, to the home. The nurse also instructs the patient and caregiver on how to administer the drug ... 

Stopping HIV is not the only avenue for research. Much work is proceeding on drugs to treat or prevent the opportunistic infections which prey upon immune deficient victims. Aerosol pentamidine was approved several years ago for the prophylaxis and treatment of pneumocystis infection. 

Obaji J, Lee-Pack LR, Gutierrez C, Chan CK The pulmonary effects of long-term exposure to aerosol pentamidine a 5-year surveillance study in HIV-infected patients. Chest. 2003 123 1983-1987. 

In lung function tests, high-dose aerosolized pentamidine (600 mg/month) was associated with an increased pulmonary residual volume, reduced flow rates, and increased airway reactivity (SEDA-18, 291). 

Megaloblastic bone marrow changes can occur with prolonged therapy (SEDA-11, 598). Low blood cell counts have been reported even after aerosolized pentamidine. 

McDiarmid MA, Fujikawa J, Schaefer J, Weinmann G, Chaisson RE, Hudson CA. Health effects and exposure assessment of aerosolized pentamidine handlers. Chest 1993 104(2) 382-5. 

Currently, pentamidine in the form of aerosol is used for the prophylaxis of PCP with apparent success [163-166]. Initially no renal side effects were described with its use. However, two reports of acute renal dysfunction raised the possibility of a systemic absorption of aerosolized pentamidine [167, 168]. One of the patients received a previous large dose of TMP-SMZ and the other appears to have had concomitant volume depletion caused by severe diarrhea while an elevation of serum creatinine occurred. We have been unable to find additional reports of renal toxicity associated with aerosol pentamidine administration[169]. Likewise, no renal side effects were reported with the use of aerosolized pentamidine for the prophylaxis of PCP in patients who received bone marrow, renal or hepatic transplants [165, 166]. Although the use of aerosolized pentamidine may be associated with renal dysfunction, this seems much less frequent compared to the parenteral administration of this drug. 

Saukkonen K, Garland R, Koziel H. Aerosolized pentamidine as alternative primary prophylaxis against Pneumocystis carinii pneumonia in adult hepatic and renal transplant recipients. Chest. 1996 May 109(5) 1250-5. 

Aerosolized Pentamidine for Treatment and Prophylaxis of Pneumocystis carinii Pneumonia in Patients with Acquired Immunodeficiency Syndrome... 

Smaldone GC, Fuhrer J, Steigbigel RT, McPeck M. Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection. Am Rev Respir Dis 1991 143(4 Pt l) 727-737. 

Patients with acquired immunodeficiency syndrome (AIDS) are susceptible to infections caused by the protozoan Pneumocystis carinii, which causes pneumonia (PCP). There is now good evidence that aerosol pentamidine is useful in treating mild PCP [195] and, even more important, that, used intermittently, it is effective as prophylaxis against PCP [196,197], Pentamidine aerosol is delivered to the alveolar space, where the P. carinii organisms are found. 

AEROSOLIZED PENTAMIDINE RATIONALE AND EXPERIMENTAL ANIMAL STUDIES... 

Despite their availability, neither dry powder nor metered-dose inhalers have been used to deliver aerosolized pentamidine. The use of metered-dose inhalers may be problematic because these devices are better suited for frequent delivery of small doses rather than intermittent delivery of the large doses that have been therapeutically successful in prophylaxis of PCP. Dry powder devices may produce an increased incidence of cough due to airway deposition. 

AEROSOLIZED PENTAMIDINE THERAPY FOR ACTIVE PNEUMOCYSTIS CARINII PNEUMONIA... 

Four pilot and three controlled studies using aerosolized pentamidine were conducted (Tables 1 and 2) [17,18,21-23], Montgomery et al. [18] studied one group of AIDS patients with PCP who had received no prior therapy [18] and a second group that was intolerant to standard therapy [22], Of the 25 patients, 23 recovered. Relapses occurred in only three patients during a mean follow-up of more than 1 year. No adverse systemic reactions were observed with aerosolized... 

Table 1 Aerosolized Pentamidine Studies for Mild-to-Moderate PCP in Patients with AIDS...

All groups used Respirgard II nebulizer for aerosolized pentamidine. 

The second study was a double-blinded comparative trial of secondary prophylaxis comparing 60 mg aerosolized pentamidine given every 2 wk after five weekly loading bases to placebo using a handheld FisoNeb ultrasonic nebulizer with a 5- xm MMAD particle size [36,37], The study was intended to run 6 mo, but it was terminated early, with a mean follow-up of only 3.7 mo. Aerosolized pentamidine significantly reduced the reoccurrence rate of PCP as compared to controls in this study [37,38]. 

Comparisons of the performance of two nebulizers in the delivery of pentamidine and their effectiveness in a community-based clinical trial have been reported [42]. The systems employed were the Respirgard II and the Fisoneb. Both systems provided comparable protection against PCP. The study supported the effectiveness of aerosolized pentamidine as a solid second-line prophylaxis for HIV-infected individuals who are tolerant to trimethoprim/sulfamethoxazole or dapsone. 

Inadequate experience has been obtained to determine the incidence of the infrequent adverse reactions that will be associated with aerosolized pentamidine therapy for acute PCP. In case reports, bronchial bleeding has been reported with high-dose therapy in one center [43]. This was associated with an invasive procedure and has not been seen in the large prospective treatment trial. Case reports of hypoglycemia, rash, and conjunctivitis have also been reported [44,45]. The conjunctivitis is not unexpected it would be the direct consequence of... 

Complications due to pentamidine administration used in prophylaxis following bone marrow transplantation have been observed [49]. Indeed, aerosolized pentamidine was associated with increased risk of other infections and decreased survival rate. 

Currently, there is a paucity of antimicrobial products delivered by aerosolization. Pentamidine and tobramycin are the only two agents approved for use in the United States as aerosolized antimicrobial therapies. However, interest in using the lung as a site of delivery of therapeutic agents has continued to evolve, and several therapies are under investigation for both local and systemic effects [2],... 

The incidence of Pneumocystis carinii pneumonia (PCP) within the first year after transplantation is reported to be 3% to 5%. " Low-dose trimethoprim-sulfamethoxazole (TMP-SMX 400 mg/ 80 mg three times weekly) is effective in the prevention of PCP infections. Alternative agents include aerosolized pentamidine (300 mg every month), dapsone, and atovaquone. The duration of PCP prophylaxis is unclear. The risk of infection caused by P. carinii is likely to decrease as immunosuppression is reduced therefore, prophylaxis in patients requiring treatment for acute rejection may be appropriate. 

For treatment of HIV-associated PCP, pentamidine isethionate is administered intravenously usually in doses of 4 mg/kg per day, although a pilot study has reported successful treatment with 3 mg/kg per day. Aerosolized pentamidine should not be used for treatment of PCP because comparative studies with intravenous pentamidine indicate that aerosolized treatment is associated with a slower clinical response and higher rates of therapeutic failure and PCP relapse. The efficacy of trimethoprim-sulfamethoxazole or pentamidine for treatment of an initial episode of PCP in HIV-infected individuals is similar, with published response rates between 60% to 80%. While comparative studies between the two regimens are few, one prospective, randomized trial found that oxygenation improved more quickly and survival was better in those who received trimethoprim-sulfamethoxazole. ... 

---