*NebuPent 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:
*NebuPent 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:
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<!--Guideline-Supported Use (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultGuideSupport=
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultNoGuideSupport=
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
|fdaLIADPed=
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedGuideSupport=
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
<!--Contraindications-->
|contraindications=*NebuPent is contraindicated in patients with a history of an [[anaphylactic]] reaction to inhaled or [[parenteral]] pentamidine isethionate.
|contraindications=
*NebuPent is contraindicated in patients with a history of an [[anaphylactic]] reaction to inhaled or [[parenteral]] pentamidine isethionate.
<!--Warnings-->
<!--Warnings-->
|warnings=*The potential for development of acute PJP still exists in patients receiving NebuPent [[prophylaxis]]. Therefore, any patient with symptoms suggestive of the presence of a [[pulmonary infection]], including but not limited to [[dyspnea]], [[fever]] or [[cough]], should receive a thorough medical evaluation and appropriate diagnostic tests for possible acute PJP as well as for other [[opportunistic]] and nonopportunistic pathogens. The use of NebuPent may alter the clinical and radiographic features of PJP and could result in an atypical presentation, including but not limited to mild disease or focal infection.
|warnings=
*The potential for development of acute PJP still exists in patients receiving NebuPent [[prophylaxis]]. Therefore, any patient with symptoms suggestive of the presence of a [[pulmonary infection]], including but not limited to [[dyspnea]], [[fever]] or [[cough]], should receive a thorough medical evaluation and appropriate diagnostic tests for possible acute PJP as well as for other [[opportunistic]] and nonopportunistic pathogens. The use of NebuPent may alter the clinical and radiographic features of PJP and could result in an atypical presentation, including but not limited to mild disease or focal infection.
*Prior to initiating NebuPent [[prophylaxis]], symptomatic patients should be evaluated appropriately to exclude the presence of PJP. The recommended dose of NebuPent for the prevention of PJP is insufficient to treat acute [[PJP]].
*Prior to initiating NebuPent [[prophylaxis]], symptomatic patients should be evaluated appropriately to exclude the presence of PJP. The recommended dose of NebuPent for the prevention of PJP is insufficient to treat acute [[PJP]].
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<!--Clinical Trials Experience-->
<!--Clinical Trials Experience-->
|clinicalTrials=*The most frequently reported unsolicited adverse events (1 to 5%) in clinical trials, regardless of their relation to NebuPent therapy were as follows (n=931):
|clinicalTrials=
*The most frequently reported unsolicited adverse events (1 to 5%) in clinical trials, regardless of their relation to NebuPent therapy were as follows (n=931):
=====Body as a Whole=====
=====Body as a Whole=====
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<!--Postmarketing Experience-->
<!--Postmarketing Experience-->
|postmarketing=*From post-marketing clinical experience with NebuPent the following spontaneous adverse events have been reported: [[anaphylaxis]], [[colitis]], [[diabetes]], [[dyspnea]], [[esophigitis]], [[hematochezia]], increased [[blood urea nitrogen]] (BUN) and serum [[creatinine]] levels, melena, [[pancreatitis]], [[syndrome of inappropriate antidiuretic hormone]] ([[SIADH]]), and [[torsade de pointes]].
|postmarketing=
*From post-marketing clinical experience with NebuPent the following spontaneous adverse events have been reported: [[anaphylaxis]], [[colitis]], [[diabetes]], [[dyspnea]], [[esophigitis]], [[hematochezia]], increased [[blood urea nitrogen]] (BUN) and serum [[creatinine]] levels, melena, [[pancreatitis]], [[syndrome of inappropriate antidiuretic hormone]] ([[SIADH]]), and [[torsade de pointes]].
<!--Drug Interactions-->
<!--Drug Interactions-->
|drugInteractions=*While specific studies on drug interactions with NebuPent have not been conducted, the majority of patients in clinical trials received concomitant medications, including [[zidovudine]], with no reported interactions. Because the [[nephrotoxic]] effects may be additive, the concomitant or sequential use of NebuPent and other [[nephrotoxic]] drugs such as [[aminoglycosides]], [[amphotericin B]], [[cisplatin]], [[foscarnet]], or [[vancomycin]] should be closely monitored and avoided, if possible.
|drugInteractions=
*While specific studies on drug interactions with NebuPent have not been conducted, the majority of patients in clinical trials received concomitant medications, including [[zidovudine]], with no reported interactions. Because the [[nephrotoxic]] effects may be additive, the concomitant or sequential use of NebuPent and other [[nephrotoxic]] drugs such as [[aminoglycosides]], [[amphotericin B]], [[cisplatin]], [[foscarnet]], or [[vancomycin]] should be closely monitored and avoided, if possible.
<!--Use in Specific Populations-->
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category C'''
|useInPregnancyFDA=
* '''Pregnancy Category C'''
*There are no adequate and well controlled studies of NebuPent in pregnant women. A literature report indicated that intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; [[teratogenicity]] was not observed in this study. It is unknown whether pentamidine administered via the aerosolized route crosses the placenta at clinically significant concentrations. It is not known whether NebuPent can cause fetal harm when administered to a [[pregnant]] woman. NebuPent should be given to a pregnant woman only if clearly needed.
*There are no adequate and well controlled studies of NebuPent in pregnant women. A literature report indicated that intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; [[teratogenicity]] was not observed in this study. It is unknown whether pentamidine administered via the aerosolized route crosses the placenta at clinically significant concentrations. It is not known whether NebuPent can cause fetal harm when administered to a [[pregnant]] woman. NebuPent should be given to a pregnant woman only if clearly needed.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=
|useInNursing=*It is not known whether NebuPent is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from NebuPent, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Because many drugs are excreted in human milk, NebuPent should not be given to a nursing mother unless the potential benefits are judged to outweigh the unknown risks.
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInPed=*The safety and effectiveness of NebuPent in pediatric patients (birth to 16 years of age) have not been established.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInNursing=
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
*It is not known whether NebuPent is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from NebuPent, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Because many drugs are excreted in human milk, NebuPent should not be given to a nursing mother unless the potential benefits are judged to outweigh the unknown risks.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInPed=
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
*The safety and effectiveness of NebuPent in pediatric patients (birth to 16 years of age) have not been established.
|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
<!--Administration and Monitoring-->
|administration=* Oral
|administration=
* Oral
* Intravenous
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
<!--IV Compatibility-->
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|IVCompat=
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|mechAction=* 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.
|mechAction=
* 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.
<!--Structure-->
<!--Structure-->
|structure=* NebuPent (pentamidine isethionate), an antifungal agent, is a nonpyrogenic lyophilized product. After reconstitution with Sterile Water for Injection, USP, NebuPent is administered by inhalation via the Respirgard® II nebulizer [Marquest, Englewood, CO].
|structure=
* NebuPent (pentamidine isethionate), an antifungal agent, is a nonpyrogenic lyophilized product. After reconstitution with Sterile Water for Injection, USP, NebuPent is administered by inhalation via the Respirgard® II nebulizer [Marquest, Englewood, CO].
*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.
*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.
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<!--Pharmacodynamics-->
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|PD=
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
<!--Pharmacokinetics-->
<!--Pharmacokinetics-->
|PK=*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).
|PK=
*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 clearance were 612 ± 371 ng/mL, 6.4 ± 1.3 hr and 248 ± 91 L/hr respectively. In another study of aerosolized pentamidine in 13 AIDS patients with acute PJP who received 4 mg/kg/day administered via the Ultra Vent® jet nebulizer, peak plasma levels of pentamidine averaged 18.8 ± 11.9 ng/mL after the first dose. During the next 14 days of repeated dosing, the highest observed Cmax averaged 20.5 ± 21.2 ng/mL. In a third study, following daily administration of 600 mg of inhaled pentamidine isethionate with the Respirgard® II nebulizer for 21 days in 11 patients with acute PJP, mean plasma levels measured shortly after the 21st dose averaged 11.8 ± 10.0 ng/mL. Plasma concentrations after aerosol administration are substantially lower than those observed after a comparable intravenous dose. The extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known.
*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 clearance were 612 ± 371 ng/mL, 6.4 ± 1.3 hr and 248 ± 91 L/hr respectively. In another study of aerosolized pentamidine in 13 AIDS patients with acute PJP who received 4 mg/kg/day administered via the Ultra Vent® jet nebulizer, peak plasma levels of pentamidine averaged 18.8 ± 11.9 ng/mL after the first dose. During the next 14 days of repeated dosing, the highest observed Cmax averaged 20.5 ± 21.2 ng/mL. In a third study, following daily administration of 600 mg of inhaled pentamidine isethionate with the Respirgard® II nebulizer for 21 days in 11 patients with acute PJP, mean plasma levels measured shortly after the 21st dose averaged 11.8 ± 10.0 ng/mL. Plasma concentrations after aerosol administration are substantially lower than those observed after a comparable intravenous dose. The extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known.
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<!--Nonclinical Toxicology-->
<!--Nonclinical Toxicology-->
|nonClinToxic=*Literature reports indicate that pentamidine was not mutagenic in the Ames bacterial (S. typhimurium) test and did not induce an increase in chromosomal aberrations in Chinese Hamster Ovary (CHO) cell or in human [[lymphocytes]] in vitro.
|nonClinToxic=
*Literature reports indicate that pentamidine was not mutagenic in the Ames bacterial (S. typhimurium) test and did not induce an increase in chromosomal aberrations in Chinese Hamster Ovary (CHO) cell or in human [[lymphocytes]] in vitro.
*No studies have been conducted to determine effects of pentamidine isethionate on carcinogenicity or fertility.
*No studies have been conducted to determine effects of pentamidine isethionate on carcinogenicity or fertility.
<!--Clinical Studies-->
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
|clinicalStudies=
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
<!--How Supplied-->
<!--How Supplied-->
|howSupplied=* Product No: 87715 63323-877-15
|howSupplied=
* Product No: 87715 63323-877-15
*NebuPent® (pentamidine isethionate) 300 mg lyophilized product in single dose vials, individually packaged.
*NebuPent® (pentamidine isethionate) 300 mg lyophilized product in single dose vials, individually packaged.
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<!--Patient Counseling Information-->
<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
|fdaPatientInfo=
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
<!--Precautions with Alcohol-->
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
<!--Brand Names-->
<!--Brand Names-->
|brandNames=* NEBUPENT®<ref>{{Cite web | title = NEBUPENT- pentamidine isethionate inhalant | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2ad9d3c-b6c3-4f70-87e0-722a8ff94ccb }}</ref>
|brandNames=
* NEBUPENT®<ref>{{Cite web | title = NEBUPENT- pentamidine isethionate inhalant | url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e2ad9d3c-b6c3-4f70-87e0-722a8ff94ccb }}</ref>
<!--Look-Alike Drug Names-->
<!--Look-Alike Drug Names-->
|lookAlike=<!--Drug Shortage Status-->
|lookAlike=
<!--Drug Shortage Status-->
|drugShortage=
|drugShortage=
}}
}}
{{PillImage
|fileName=No image.jpg
}}
<!--Pill Image-->
<!--Pill Image-->
{{PillImage
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NebuPent 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:
a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm3.
Dosing Information
The recommended adult dosage of NebuPent for the prevention of Pneumocystis jiroveci pneumonia is 300 mg once every four weeks administered via the Respirgard® II nebulizer.
The dose should be delivered until the nebulizer chamber is empty (approximately 30 to 45 minutes). The flow rate should be 5 to 7 liters per minute from a 40 to 50 pounds per square inch (PSI) air or oxygen source. Alternatively, a 40 to 50 PSI air compressor can be used with flow limited by setting the flowmeter at 5 to 7 liters per minute or by setting the pressure at 22 to 25 PSI. Low pressure (less than 20 PSI) compressors should not be used.
Stability
Freshly prepared solutions for aerosol use are recommended. After reconstitution with sterile water, the NebuPent solution is stable for 48 hours in the original vial at room temperature if protected from light.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pentamidine (inhalation) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pentamidine (inhalation) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Pentamidine (inhalation) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pentamidine (inhalation) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pentamidine (inhalation) in pediatric patients.
Contraindications
NebuPent is contraindicated in patients with a history of an anaphylactic reaction to inhaled or parenteral pentamidine isethionate.
Warnings
The potential for development of acute PJP still exists in patients receiving NebuPent prophylaxis. Therefore, any patient with symptoms suggestive of the presence of a pulmonary infection, including but not limited to dyspnea, fever or cough, should receive a thorough medical evaluation and appropriate diagnostic tests for possible acute PJP as well as for other opportunistic and nonopportunistic pathogens. The use of NebuPent may alter the clinical and radiographic features of PJP and could result in an atypical presentation, including but not limited to mild disease or focal infection.
Prior to initiating NebuPent prophylaxis, symptomatic patients should be evaluated appropriately to exclude the presence of PJP. The recommended dose of NebuPent for the prevention of PJP is insufficient to treat acute PJP.
Precautions
Pulmonary
Inhalation of NebuPent may induce bronchospasm or cough. This has been noted particularly in some patients who have a history of smoking or asthma. In clinical trials, cough and bronchospasm were the most frequently reported adverse experiences associated with NebuPent administration (38% and 15%, respectively of patients receiving the 300 mg dose); however less than 1% of the doses were interrupted or terminated due to these effects. For the majority of patients, cough and bronchospasm were controlled by administration of an aerosolized bronchodilator (only 1% of patients withdrew from the study due to treatment-associated cough or bronchospasm). In patients who experience bronchospasm or cough, administration of an inhaled bronchodilator prior to giving each NebuPent dose may minimize recurrence of the symptoms.
Extrapulmonary infection with P. jiroveci has been reported infrequently. Most, but not all, of the cases have been reported in patients who have a history of PJP. The presence of extrapulmonarypneumocystosis should be considered when evaluating patients with unexplained signs and symptoms.
Cases of acute pancreatitis have been reported in patients receiving aerosolized pentamidine. NebuPent should be discontinued if signs or symptoms of acute pancreatitis develop.
Adverse Reactions
Clinical Trials Experience
The most frequently reported unsolicited adverse events (1 to 5%) in clinical trials, regardless of their relation to NebuPent therapy were as follows (n=931):
While specific studies on drug interactions with NebuPent have not been conducted, the majority of patients in clinical trials received concomitant medications, including zidovudine, with no reported interactions. Because the nephrotoxic effects may be additive, the concomitant or sequential use of NebuPent and other nephrotoxic drugs such as aminoglycosides, amphotericin B, cisplatin, foscarnet, or vancomycin should be closely monitored and avoided, if possible.
There are no adequate and well controlled studies of NebuPent in pregnant women. A literature report indicated that intravenously administered pentamidine in pregnant rats at 4 mg/kg/day was embryolethal; teratogenicity was not observed in this study. It is unknown whether pentamidine administered via the aerosolized route crosses the placenta at clinically significant concentrations. It is not known whether NebuPent can cause fetal harm when administered to a pregnant woman. NebuPent should be given to a pregnant woman only if clearly needed.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pentamidine (inhalation) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Pentamidine (inhalation) during labor and delivery.
Nursing Mothers
It is not known whether NebuPent is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from NebuPent, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Because many drugs are excreted in human milk, NebuPent should not be given to a nursing mother unless the potential benefits are judged to outweigh the unknown risks.
Pediatric Use
The safety and effectiveness of NebuPent in pediatric patients (birth to 16 years of age) have not been established.
Geriatic Use
There is no FDA guidance on the use of Pentamidine (inhalation) with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Pentamidine (inhalation) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Pentamidine (inhalation) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Pentamidine (inhalation) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Pentamidine (inhalation) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pentamidine (inhalation) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Pentamidine (inhalation) in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
There is limited information regarding Monitoring of Pentamidine (inhalation) in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Pentamidine (inhalation) in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Overdosage has not been reported with NebuPent. The symptoms and signs of overdosage are not known.
A serious overdosage, to the point of producing systemic drug levels similar to those following parenteral administration, would have the potential of producing similar types of serious systemic toxicity.
Available clinical pharmacology data suggest that a dose up to 40 times the recommended NebuPent dosage would be required to produce systemic levels similar to a single 4 mg/kg intravenous dose.
Chronic Overdose
There is limited information regarding Chronic Overdose of Pentamidine (inhalation) in the drug label.
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.
Structure
NebuPent (pentamidine isethionate), an antifungal agent, is a nonpyrogenic lyophilized product. After reconstitution with Sterile Water for Injection, USP, NebuPent is administered by inhalation via the Respirgard® II nebulizer [Marquest, Englewood, CO].
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.
There is limited information regarding Pharmacodynamics of Pentamidine (inhalation) in the drug label.
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 clearance were 612 ± 371 ng/mL, 6.4 ± 1.3 hr and 248 ± 91 L/hr respectively. In another study of aerosolized pentamidine in 13 AIDS patients with acute PJP who received 4 mg/kg/day administered via the Ultra Vent® jet nebulizer, peak plasma levels of pentamidine averaged 18.8 ± 11.9 ng/mL after the first dose. During the next 14 days of repeated dosing, the highest observed Cmax averaged 20.5 ± 21.2 ng/mL. In a third study, following daily administration of 600 mg of inhaled pentamidine isethionate with the Respirgard® II nebulizer for 21 days in 11 patients with acute PJP, mean plasma levels measured shortly after the 21st dose averaged 11.8 ± 10.0 ng/mL. Plasma concentrations after aerosol administration are substantially lower than those observed after a comparable intravenous dose. The extent of pentamidine accumulation and distribution following chronic inhalation therapy are not known.
In rats, intravenous administration of a 5 mg/kg dose resulted in concentrations of pentamidine in the liver and kidney that were 87.5 and 62.3-fold higher, respectively, than levels in those organs following 5 mg/kg administered as an aerosol.
No pharmacokinetic data are available following aerosol administration of pentamidine in humans with impaired hepatic or renal function.
Nonclinical Toxicology
Literature reports indicate that pentamidine was not mutagenic in the Ames bacterial (S. typhimurium) test and did not induce an increase in chromosomal aberrations in Chinese Hamster Ovary (CHO) cell or in human lymphocytes in vitro.
No studies have been conducted to determine effects of pentamidine isethionate on carcinogenicity or fertility.
Clinical Studies
There is limited information regarding Clinical Studies of Pentamidine (inhalation) in the drug label.
How Supplied
Product No: 87715 63323-877-15
NebuPent® (pentamidine isethionate) 300 mg lyophilized product in single dose vials, individually packaged.
Store dry product at 20°to 25°C (68°to 77°F).
Protect the dry product and the reconstituted solution from light.
Storage
There is limited information regarding Pentamidine (inhalation) Storage in the drug label.
Images
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