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| {{DrugProjectFormSinglePage
| | #REDIRECT [[Pentamidine]] |
| |authorTag=
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| {{VP}}
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| <!--Overview-->
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| |genericName=
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| Pentamidine isethionate
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| |aOrAn=
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| an
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| |drugClass=
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| antifungal
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| |indication=
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| [[pneumocystis jiroveci pneumonia]]
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| |hasBlackBoxWarning=
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| |adverseReactions=
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| [[night sweats]], [[anemia]], [[nausea]], [[diarrhea]]
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| <!--Black Box Warning-->
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| |blackBoxWarningTitle=
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| Title
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| |blackBoxWarningBody=
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| <i><span style="color:#FF0000;">ConditionName: </span></i>
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| * Content
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| <!--Adult Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Adult)-->
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| |fdaLIADAdult=
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| =====Pneumocystis jiroveci Pneumonia=====
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| *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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| :*a history of one or more episodes of PJP
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| :*a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm3.
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| * Dosing Information
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| :*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.
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| :*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.
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| *Stability
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| :*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.
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| <!--Off-Label Use and Dosage (Adult)-->
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| <!--Guideline-Supported Use (Adult)-->
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| |offLabelAdultGuideSupport=
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Non–Guideline-Supported Use (Adult)-->
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| |offLabelAdultNoGuideSupport=
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Pediatric Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Pediatric)-->
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| |fdaLIADPed=
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| There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Off-Label Use and Dosage (Pediatric)-->
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| <!--Guideline-Supported Use (Pediatric)-->
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| |offLabelPedGuideSupport=
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Non–Guideline-Supported Use (Pediatric)-->
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| |offLabelPedNoGuideSupport=
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Contraindications-->
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| |contraindications=
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| *NebuPent is contraindicated in patients with a history of an [[anaphylactic]] reaction to inhaled or [[parenteral]] pentamidine isethionate.
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| <!--Warnings-->
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| |warnings=
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| *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.
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| *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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| ====Precautions====
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| *Pulmonary
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| :*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.
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| *General
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| :*The extent and consequence of pentamidine accumulation following chronic inhalation therapy are not known. As a result, patients receiving NebuPent should be closely monitored for the development of serious adverse reactions that have occurred in patients receiving parenteral pentamidine, including [[hypotension]], [[hypoglycemia]], [[hyperglycemia]], [[hypocalcemia]], [[anemia]], [[thrombocytopenia]], [[leukopenia]], hepatic or renal dysfunction, [[ventricular tachycardia]], [[pancreatitis]], [[Stevens-Johnson syndrome]], [[hyperkalemia]] and abnormal [[ST segment]] of [[ECG]].
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| :*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 extrapulmonary pneumocystosis should be considered when evaluating patients with unexplained signs and symptoms.
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| :*Cases of acute pancreatitis have been reported in patients receiving aerosolized pentamidine. NebuPent should be discontinued if signs or symptoms of acute [[pancreatitis]] develop.
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| <!--Adverse Reactions-->
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| <!--Clinical Trials Experience-->
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| |clinicalTrials=
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| *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):
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| =====Body as a Whole=====
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| [[Night sweats]].
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| =====Gastrointestinal=====
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| [[Diarrhea]] and [[nausea]].
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| =====Hematologic=====
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| [[Anemia]].
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| =====Infection=====
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| [[Bronchitis]], non-specific [[herpes]], [[herpes zoster]], non-specific [[influenza]], oral [[Candida]], [[pharyngitis]], [[sinusitis]], and upper respiratory tract.
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| =====Nervous System=====
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| [[Headache]].
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| =====Respiratory System=====
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| [[Chest pain]], [[cough]], and [[wheezing]].
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| =====Special Senses=====
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| Bad taste.
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| *Adverse events of less than 1% incidence were as follows (No causal relationship to treatment has been established for these adverse events):
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| =====Body as a Whole=====
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| Allergic reaction, non-specific allergy, body odor, facial [[edema]], fever, leg edema, [[lethargy]], low body temperature, and temperature abnormality.
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| =====Cardiovascular=====
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| Cerebrovascular accident, [[hypotension]], [[hypertension]], [[palpitations]], poor circulation, [[syncope]], [[tachycardia]], [[vasodilatation]] and [[vasculitis]].
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| =====Gastrointestinal=====
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| [[Abdominal cramps]], [[abdominal pain]], [[constipation]], dry mouth, [[dyspepsia]], [[gastritis]], [[gastric ulcer]], [[gingivitis]], [[hiatal hernia]], hypersalivation, oral ulcer/abscess, [[splenomegaly]], and [[vomiting]].
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| =====Hematological=====
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| [[Eosinophilia]], [[neutropenia]], non-specific [[cytopenia]], [[pancytopenia]], and [[thrombocytopenia]].
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| =====Hepatic=====
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| [[Hepatitis]], [[hepatomegaly]], and hepatic dysfunction.
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| =====Infection=====
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| [[Bacterial pneumonia]], central venous line related [[sepsis]], [[cryptococcal meningitis]], [[cytomegalovirus]] (CMV) [[colitis]], CMV [[retinitis]], esophageal [[Candida]], [[histoplasmosis]], [[Kaposi’s sarcoma]], non-specific [[mycoplasma]], oral herpes, non-specific [[otitis]], non-specific [[pharyngitis]], pharyngeal herpes, non-specific serious infection, [[tonsillitis]], [[tuberculosis]], and [[viral encephalitis]].
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| =====Metabolic=====
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| [[Hyperglycemia]], [[hypoglycemia]], and [[hypocalcemia]].
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| =====Musculoskeletal=====
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| [[Arthralgia]], [[gout]], and [[myalgia]].
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| =====Neurological=====
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| Anxiety, confusion, depression, drowsiness, emotional lability, hallucination, hypesthesia, insomnia, memory loss, [[neuralgia]], neuropathy, non-specific neuropathy, nervousness, paranoia, [[paresthesia]], [[peripheral neuropathy]], [[seizure]], tremors, unsteady [[gait]], and [[vertigo]].
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| =====Reproductive=====
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| [[Miscarriage]].
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| =====Respiratory system=====
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| [[Asthma]], [[bronchitis]], [[bronchospasm]], chest congestion, chest tightness, [[coryza]], [[cyanosis]], eosinophilic or interstitial [[pneumonitis]], gagging, [[hemoptysis]], [[hyperventilation]], [[laryngitis]], [[laryngospasm]], non-specific lung disorder, nasal congestion, [[pleuritis]], [[pneumothorax]], rales, rhinitis, shortness of breath, non-specific sputum, and [[tachypnea]].
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| =====Skin=====
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| [[Desquamation]], dry and breaking hair, dry skin, [[erythema]], non-specific [[dermatitis]], [[pruritus]], rash, and [[urticaria]].
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| =====Special senses=====
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| [[Blepharitis]], blurred vision, [[conjunctivitis]], contact lens discomfort, eye pain or discomfort, hemianopsia, loss of taste, non-specific odor, and smell.
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| =====Urogenital=====
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| [[Flank pain]], [[incontinence]], [[nephritis]], [[renal failure]], and renal pain.
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| *In a clinical trial where some adverse events were solicited by investigators, the incidences were as follows:
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| :*[[Cough]] (62.7%)
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| :*Decreased appetite (50.0%)
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| :*Dizziness or light-headedness (45.1%)
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| :*Fatigue (65.7%)
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| :*[[Fever]] (51.0%)
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| :*Non-specific serious infection (15.2%)
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| :*Shortness of breath (48.3%)
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| :*[[Wheezing]] (32.4%)
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| <!--Postmarketing Experience-->
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| |postmarketing=
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| *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 (see WARNINGS), syndrome of inappropriate antidiuretic hormone (SIADH), and torsade de pointes.
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| <!--Drug Interactions-->
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| |drugInteractions=
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| *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.
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| <!--Use in Specific Populations-->
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| |useInPregnancyFDA=
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| * '''Pregnancy Category C'''
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| *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.
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| |useInPregnancyAUS=
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| * '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
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| There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
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| |useInLaborDelivery=
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| There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
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| |useInNursing=
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| *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.
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| |useInPed=
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| *The safety and effectiveness of NebuPent in pediatric patients (birth to 16 years of age) have not been established.
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| |useInGeri=
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| There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
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| |useInGender=
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| There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
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| |useInRace=
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| There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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| |useInRenalImpair=
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| There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
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| |useInHepaticImpair=
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| There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
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| |useInReproPotential=
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| There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
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| |useInImmunocomp=
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| There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
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| <!--Administration and Monitoring-->
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| |administration=
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| * Oral
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| * Intravenous
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| |monitoring=
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| There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
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| * Description
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| <!--IV Compatibility-->
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| |IVCompat=
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| There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
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| <!--Overdosage-->
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| |overdose=
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| ===Acute Overdose===
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| ====Signs and Symptoms====
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| *Overdosage has not been reported with NebuPent. The symptoms and signs of overdosage are not known.
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| *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.
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| *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.
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| ===Chronic Overdose===
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| There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
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| <!--Pharmacology-->
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| <!--Drug box 2-->
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| |drugBox=
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| <!--Mechanism of Action-->
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| |mechAction=
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| * 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.
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| <!--Structure-->
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| |structure=
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| * 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].
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| *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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| : [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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| <!--Pharmacodynamics-->
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| |PD=
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| There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
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| <!--Pharmacokinetics-->
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| |PK=
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| *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).
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| *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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| *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.
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| *No pharmacokinetic data are available following aerosol administration of pentamidine in humans with impaired hepatic or renal function.
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| <!--Nonclinical Toxicology-->
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| |nonClinToxic=
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| *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.
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| *No studies have been conducted to determine effects of pentamidine isethionate on carcinogenicity or fertility.
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| <!--Clinical Studies-->
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| |clinicalStudies=
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| There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
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| <!--How Supplied-->
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| |howSupplied=
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| * 87715 63323-877-15
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| *NebuPent® (pentamidine isethionate) 300 mg lyophilized product in single dose vials, individually packaged.
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| *Store dry product at 20°to 25°C (68°to 77°F).
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| *Protect the dry product and the reconstituted solution from light.
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| <!--Patient Counseling Information-->
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| |fdaPatientInfo=
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| There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
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| <!--Precautions with Alcohol-->
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| |alcohol=
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| * Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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| <!--Brand Names-->
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| |brandNames=
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| * 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>
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| <!--Look-Alike Drug Names-->
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| |lookAlike=
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| <!--Drug Shortage Status-->
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| |drugShortage=
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| }}
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| <!--Pill Image-->
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| {{PillImage
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| |fileName=No image.jpg|This image is provided by the National Library of Medicine.
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| |drugName=
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| |NDC=
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| |drugAuthor=
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| |ingredients=
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| |pillImprint=
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| |dosageValue=
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| |dosageUnit=
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| |pillColor=
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| |pillShape=
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| |pillSize=
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| |pillScore=
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| }}
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| <!--Label Display Image-->
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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| }}
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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| }}
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| <!--Category-->
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| [[Category:Drug]]
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