Pentamidine Isethionate

Class: Antiprotozoals, Miscellaneous
VA Class: AP100
Chemical Name: 4,4′-[1,5-Pentanediylbis(oxy)]bisbenzenecarboximidamide dimethanesulfonate
CAS Number: 140-64-7
Brands: NebuPent, Pentam

Introduction

Antiprotozoal and antifungal; aromatic diamidine derivative.1 2 3 219

Uses for Pentamidine Isethionate

Pneumocystis jirovecii Pneumonia

Alternative for treatment and prevention of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP).1 134 155 156 219 Designated an orphan drug by FDA for treatment and prevention of PCP in patients at high risk for the disease.79 134

Co-trimoxazole is drug of choice for treatment of mild, moderate, or severe PCP in adults, adolescents, and children, including HIV-infected individuals.134 155 156

CDC, NIH, and IDSA recommend IV pentamidine or regimen of primaquine in conjunction with clindamycin as alternatives for treatment of moderate to severe PCP in HIV-infected adults and adolescents who cannot tolerate or have not responded to co-trimoxazole.155 Some clinicians prefer primaquine and clindamycin regimen since it may be more effective and associated with lower toxicity compared with IV pentamidine.155 For treatment of PCP in HIV-infected children who cannot tolerate co-trimoxazole or have not responded after 5–7 days of co-trimoxazole, CDC, NIH, IDSA, and AAP recommend IV pentamidine;156 treatment can be switched to appropriate oral regimen (e.g., atovaquone) after initial response is obtained with IV pentamidine.156

CDC, NIH, IDSA, and AAP recommend pentamidine given by oral inhalation via nebulization (aerosolized pentamidine) as one of several alternatives for prevention of initial episode of PCP (primary prophylaxis) and for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of PCP in HIV-infected adults, adolescents, and children ≥5 years of age who cannot tolerate drug of choice (co-trimoxazole).155 156

African Trypanosomiasis

Treatment of early or first-stage (hemolymphatic) trypanosomiasis caused by Trypanosoma brucei gambiense (West African trypanosomiasis, gambiense sleeping sickness).2 41 42 43 44 100 101 102 103 107 134 367 368 369 Drug of choice for first-stage T. b. gambiense infection;44 134 367 368 suramin (not commercially available in US, but may be available from CDC) also effective for first-stage disease, but considered an alternative since pentamidine is better tolerated.134 367

Has been used for treatment of early or first-stage (hemolymphatic) trypanosomiasis caused by T. b. rhodesiense (East African trypanosomiasis, rhodesiense sleeping sickness).43 44 134 149 150 367 368 Suramin (not commercially available in US, but may be available from CDC) usually drug of choice for first-stage T. b. rhodesiense infection;44 134 367 368 pentamidine is an alternative,43 44 367 but may be less effective in these infections than in T. b. gambiense infections.41 42 43 44 44 134 367 368

Slideshow: Aging Issues: 12 of the Most Common Health Concerns Affecting Seniors

Do not use for treatment of second-stage (meningoencephalitic) T. b. gambiense or T. b. rhodesiense infections with CNS involvement since pentamidine penetrates CNS poorly.15 42 43 44 100 101 102 103 105 134 146 367 368 369 Eflornithine (with or without nitfurtimox) or melarsoprol (drugs not commercially available in US, but may be available from CDC) usually recommended for T. b. gambiense infection with CNS involvement;44 134 368 369 melarsoprol (not commercially available in US, but may be available from CDC) usually recommended for treatment of T. b. rhodesiense infection with CNS involvement.134 367 368

T. b. gambiense and T. b. rhodesiense transmitted to humans by bite of infected tsetse flies;44 105 377 transmission via blood or perinatal transmission from mother to infant is rare.377 T. b. gambiense is endemic in West and Central Africa;44 105 377 T. b. rhodesiense is endemic in Eastern and Southern Africa.44 105 377 Trypanosomiasis reported in short-term travelers to endemic areas and in immigrants and expatriates from such areas.44 105 368

For assistance with diagnosis or treatment of trypanosomiasis in the US, contact CDC Parasitic Diseases Hotline at 404-718-4745 from 8:00 a.m. to 4:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after business hours and on weekends and holidays.382 Contact CDC Drug Service at 404-639-3670 for information on how to obtain antiparasitic drugs not commercially available in US.382

Leishmaniasis

Has been used for treatment of cutaneous and mucocutaneous leishmaniasis caused by various Leishmania spp.46 55 56 57 105 114 154 256 369 372 373 374 When systemic treatment indicated, pentavalent antimonials (i.e., sodium stibogluconate or meglumine antimonate [drugs not commercially available in US, but may be available from CDC]) usually used;126 134 256 271 369 371 373 374 other options include amphotericin B, miltefosine, pentamidine, and ketoconazole. 46 126 134 155 369 371 373 374 Although pentamidine has been recommended for treatment of New World cutaneous leishmaniasis caused by L. guyanensis or L. panamensis,369 372 373 374 variable efficacy and potential adverse effects limit its usefulness for other types of cutaneous leishmaniasis.46 372 373 374

Has been used for treatment of visceral leishmaniasis (also known as kala-azar).46 136 137 138 152 153 256 375 376 Pentavalent antimonials (i.e., sodium stibogluconate or meglumine antimonate [drugs not commercially available in US, but may be available from CDC]) have historically been considered drugs of first choice for initial treatment of visceral leishmaniasis,46 58 126 256 271 371 375 376 but drug resistance and treatment failures are concerns in some areas (e.g., India, Nepal).126 256 375 376 Other options include amphotericin B, miltefosine, or paromomycin.126 134 155 256 271 371 375 376 Pentamidine not usually recommended because of variable or suboptimal efficacy and potential adverse effects.134 155 371 375 376

Leishmaniasis is caused by >15 different Leishmania species that are transmitted to humans by bite of infected sand flies;46 105 126 371 372 373 377 also can be transmitted via blood (e.g., blood transfusions, needles shared by IV drug abusers) and perinatally from mother to infant.46 105 155 371 377 In Eastern Hemisphere (Old World), leishmaniasis found most frequently in parts of Asia, the Middle East, Africa, and southern Europe; in Western Hemisphere (New World), found most frequently in Mexico and Central and South America and reported occasionally in Texas and Oklahoma.377 Leishmaniasis reported in short-term travelers to endemic areas and in immigrants and expatriates from such areas;46 105 372 373 377 also reported in US military personnel and contract workers serving or working in endemic areas (e.g., Iraq, Afghanistan).46 105 377

Specific form of leishmaniasis and disease severity depend on Leishmania species involved, geographic area of origin, location of sand fly bite, and patient factors (e.g., nutritional and immune status).46 105 126 371 372 373 374 375 Treatment (e.g., drug, dosage, duration of treatment) must be individualized based on region where disease was acquired, likely infecting species, drug susceptibilities reported in area of origin, form of disease, and patient factors (e.g., age, pregnancy, immune status).46 105 134 155 371 372 374 375 377 No single treatment approach is appropriate for all possible clinical presentations.46 Consultation with clinicians experienced in management of leishmaniasis recommended.105 134 371 377

For assistance with diagnosis or treatment of leishmaniasis in the US, contact CDC Parasitic Diseases Hotline at 404-718-4745 from 8:00 a.m. to 4:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after business hours and on weekends and holidays.382 Contact CDC Drug Service at 404-639-3670 for information on how to obtain antiparasitic drugs not commercially available in US.382

Babesiosis

Has been used in some patients for treatment of babesiosis caused by Babesia microti;115 116 117 118 119 efficacy not established.115 120

Has been used in conjunction with co-trimoxazole for treatment of infection caused by B. divergens,178 282 but adverse effects associated with pentamidine limit use of this regimen.178

When anti-infective treatment of babesiosis indicated, IDSA and others recommend regimen of clindamycin and quinine or regimen of atovaquone and azithromycin.105 134 178

Pentamidine Isethionate Dosage and Administration

Administration

Administer by IM injection or slow IV infusion.1

Administer by oral inhalation via nebulization.219

IV infusion (not IM injection) usually recommended for treatment of PCP;134 155 156 oral inhalation via nebulization used only for prevention of PCP.155 156 219

Since sudden, severe hypotensive reactions can occur following IV or IM administration, keep patient in supine position and closely monitor BP during and after administration.1 (See Hypotension and Other Cardiovascular Effects under Cautions.)

IV Infusion

Position IV needle or catheter carefully; observe throughout period of administration.1 Avoid extravasation;1 if extravasation occurs, immediately stop infusion and restart at another site.1 (See Local Effects under Cautions.)

Reconstitution and Dilution

For IV infusion, reconstitute vial containing 300 mg of pentamidine isethionate for IM or IV use with 3, 4, or 5 mL of sterile water for injection or 5% dextrose injection at 22–30°C to provide a solution containing 100, 75, or 60 mg/mL, respectively.1 Do not reconstitute using sodium chloride solution; precipitation will occur.1

Withdraw desired dose of reconstituted solution and dilute in 50–250 mL of 5% dextrose injection.1

Rate of Administration

Give IV infusion over 60–120 minutes.1 Do not administer by rapid IV injection or infusion.1 124 (See Hypotension and Other Cardiovascular Effects under Cautions.)

IM Injection

Administer by deep IM injection.1

Some clinicians suggest that local adverse effects may be minimized by using Z-tract technique (i.e., firmly push subcutaneous tissue aside before inserting needle at 90-degree angle).321

Reconstitution

For IM injection, reconstitute vial containing 300 mg of pentamidine isethionate for IM or IV use with 3 mL of sterile water for injection at 22–30°C to provide a solution containing 100 mg/mL.1 Do not reconstitute using sodium chloride solution; precipitation will occur.1

Oral Inhalation via Nebulization

For oral inhalation via nebulization (aerosolized pentamidine), powder for oral inhalation solution (NebuPent) is reconstituted and administered using a Respirgard II jet nebulizer.219 231 255

Consult manufacturer's information for detailed instructions regarding use and operation of the nebulizer.219 231 255

Do not admix reconstituted pentamidine solution for oral inhalation with any other drugs;219 do not use Respirgard II jet nebulizer to administer a bronchodilator.219

Reconstitution

Reconstitute vial containing 300 mg of pentamidine isethionate for oral inhalation with 6 mL of sterile water for injection.219 Do not use sodium chloride solution; precipitation will occur.219

Rate of Administration

Place entire contents of reconstituted vial into reservoir of Respirgard II jet nebulizer and deliver until nebulizer chamber is empty (approximately 30–45 minutes) using a flow rate of 5–7 L/minute and an air or oxygen source at 40–50 PSI.219 231 Alternatively, use an air compressor delivering 40–50 PSI by setting the flowmeter at 5–7 L/minute or the pressure at 22–25 PSI; low-pressure (i.e., less than 20 PSI) air compressors should not be used.219

Dosage

Available as pentamidine isethionate; dosage expressed as pentamidine isethionate.1 219

Pediatric Patients

Pneumocystis jirovecii Pneumonia (PCP)
Treatment of PCP
IM or IV

Children >4 months of age: 4 mg/kg once daily.1 156 CDC, NIH, IDSA, and AAP recommend IV route in HIV-infected children;155 if clinical improvement occurs after 7–10 days, can switch to appropriate oral regimen (e.g., atovaquone) to complete 21 days of treatment.156

Adolescents: 4 mg/kg once daily.1 155 CDC, NIH, and IDSA recommend IV route in HIV-infected adolescents;155 dosage can be reduced to 3 mg/kg IV once daily if necessary because of toxicity.155

CDC, NIH, IDSA, and AAP recommend total treatment duration of 21 days;155 156 manufacturer recommends 14–21 days and cautions that >21 days may be associated with increased toxicity.1

Prevention of Initial Episode (Primary Prophylaxis) of PCP
Oral Inhalation via Nebulization

Children ≥5 years of age: 300 mg once every 4 weeks (once monthly).156

Adolescents: 300 mg once every 4 weeks (once monthly).155

HIV-infected children 1 to <6 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <500/mm3 or CD4+ percentage <15%.156

HIV-infected children 6–12 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <200/mm3 or CD4+ percentage <15%.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing primary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Prevention of Recurrence (Secondary Prophylaxis) of PCP
Oral Inhalation via Nebulization

Children ≥5 years of age: 300 mg once every 4 weeks (once monthly).156

Adolescents: 300 mg once every 4 weeks (once monthly).155

Initiate secondary PCP prophylaxis in all HIV-infected infants and children with a history of PCP.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 month; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing secondary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

African Trypanosomiasis
Treatment of First-stage Trypanosoma brucei gambiense Infection
IM or IV

4 mg/kg once daily for 7–10 days recommended by WHO and others.44 134 367 368 369 Give IM44 134 367 368 369 or, alternatively, by IV infusion over 2 hours.44 367 368

Treatment of First-stage Trypanosoma brucei rhodesiense Infection
IM or IV

4 mg/kg once daily for 7 days recommended by WHO.44 Give IM or, alternatively, by IV infusion over 2 hours.44

Leishmaniasis
Treatment of Cutaneous Leishmaniasis
IM or IV

2–3 mg/kg once daily or every other day for 4–7 doses.134 369 Alternatively, 3–4 mg/kg once every other day for 4–10 doses.373 374

New World cutaneous leishmaniasis caused by L. guyanensis or L. panamensis: 4 mg/kg once every other day for 3 doses recommended by WHO.46

Treatment of Visceral Leishmaniasis
IM or IV

4 mg/kg once every other day or 3 times weekly for 15–20 doses.375

Adults

Pneumocystis jirovecii Pneumonia (PCP)
Treatment of Moderate to Severe PCP
IM or IV

4 mg/kg once daily.1 155 CDC, NIH, and IDSA recommend IV route in HIV-infected adults;155 dosage can be reduced to 3 mg/kg IV once daily if necessary because of toxicity.155

CDC, NIH, and IDSA recommend total treatment duration of 21 days;155 manufacturer recommends 14–21 days and cautions that >21 days may be associated with increased toxicity.1

Prevention of Initial Episode (Primary Prophylaxis) of PCP
Oral Inhalation via Nebulization

300 mg once every 4 weeks (once monthly).155 219

Initiate primary PCP prophylaxis in HIV-infected adults with CD4+ T-cell counts <200/mm3 or a history of oropharyngeal candidiasis.155 Also consider primary PCP prophylaxis if CD4+ T-cell percentage <14% or there is a history of an AIDS-defining illness.155 Also consider in those with CD4+ T-cell counts >200/mm3 but <250/mm3 if frequent monitoring (e.g., every 3 months) not possible.155

Discontinue primary PCP prophylaxis in HIV-infected adults responding to antiretroviral therapy who have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155

Reinitiate primary PCP prophylaxis if CD4+ T-cell count decreases to <200/mm3.155

Prevention of Recurrence (Secondary Prophylaxis) of PCP
Oral Inhalation via Nebulization

300 mg once every 4 weeks (once monthly).155 219

Initiate secondary PCP prophylaxis in all HIV-infected adults with a history of PCP.155

Consider discontinuing secondary PCP prophylaxis in HIV-infected adults who have responded to antiretroviral therapy and have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155 Reinitiate if CD4+ T-cell count decreases to <200/mm3 or PCP recurs when CD4+ T-cell count >200/mm3.155

Consider continuing secondary PCP prophylaxis for life (regardless of CD4+ T-cell count) if PCP occurred or recurred when CD4+ T-cell count >200/mm3.155

African Trypanosomiasis
Treatment of First-stage Trypanosoma brucei gambiense Infection
IM or IV

4 mg/kg once daily for 7–10 days recommended by WHO and others.44 134 367 368 369 Give IM44 134 367 368 369 or, alternatively, by IV infusion over 2 hours.44 367 368

Treatment of First-stage Trypanosoma brucei rhodesiense Infection
IM or IV

4 mg/kg once daily for 7 days recommended by WHO.44 Give IM or, alternatively, by IV infusion over 2 hours.44

Leishmaniasis
Treatment of Cutaneous Leishmaniasis
IM or IV

2–3 mg/kg once daily or every other day for 4–7 doses.134 369 Alternatively, 3–4 mg/kg once every other day for 4–10 doses.373 374

New World cutaneous leishmaniasis caused by L. guyanensis or L. panamensis: 4 mg/kg once every other day for 3 doses recommended by WHO.46

Treatment of Visceral Leishmaniasis
IM or IV

4 mg/kg once every other day or 3 times weekly for 15–20 doses.375

Special Populations

Hepatic Impairment

Manufacturer states use IM or IV pentamidine with caution in patients with hepatic impairment; safety and efficacy of alternative dosage regimens not established in these patients.1

Renal Impairment

Manufacturer states use IM or IV pentamidine with caution in patients with renal impairment; safety and efficacy of alternative dosage regimens not established in these patients.1

If IV pentamidine used for treatment of PCP in HIV-infected adults or adolescents with renal impairment, some clinicians recommend 3 mg/kg once every 24 hours in those with Clcr 10–50 mL/minute and 4 mg/kg once every 48 hours in those with Clcr <10 mL/minute.155

Cautions for Pentamidine Isethionate

Contraindications

  • IV or IM: Known hypersensitivity to pentamidine.1

  • Oral inhalation via nebulization: History of anaphylactic reaction to pentamidine administered parenterally or by oral inhalation.219

Warnings/Precautions

Warnings

Hypotension and Other Cardiovascular Effects

IV or IM: Hypotension, which may develop suddenly and may be moderate to severe, can occur.1 15 41 43 52 83 86 124 159 167 188 202 279 Fatalities due to severe hypotension or cardiac arrhythmias reported.1 202 Hypotensive reactions most likely with rapid IV injection or infusion.1 15 21 124 159 188 202 279

Oral inhalation via nebulization: Hypotension, hypertension, and cardiac arrhythmias also reported rarely.219 278

When administering IM or IV, place patient in a supine position.1 Monitor BP during and after administration until stable; perform ECG before, during, and after administration.1

Appropriate equipment for maintenance of an adequate airway and other supportive measures and agents (e.g., IV fluids, vasopressor agents)124 159 for management of hypotensive reactions should be readily available.1

Use with caution in patients with hypertension, hypotension, or ventricular tachycardia.1

Local Effects

IV: Extravasation may result in ulceration, tissue necrosis, and/or sloughing at injection site; long-term sequelae reported.1 Properly position and closely observe IV needle and catheter throughout infusion; if extravasation occurs, immediately discontinue infusion and restart in another vein.1 Phlebitis also reported.183

IM: Sterile abscess and/or necrosis,1 81 83 86 124 pain,1 83 124 erythema,85 89 tenderness,85 89 and induration at injection site.1 85 89

Hypoglycemia and Diabetogenic Effects

Hypoglycemia, which may be severe and has been fatal in some cases, reported with IM or IV pentamidine.1 31 32 33 34 35 81 83 84 85 86 89 90 165 167 169 180 188 202 243 Has been associated with pancreatic islet cell necrosis and inappropriately high plasma insulin concentrations.1

Hyperglycemia1 81 83 167 and insulin-dependent diabetes mellitus1 31 35 52 275 (which appears to be permanent in some cases)52 has occurred with or without preceding hypoglycemia1 275 and ketoacidosis1 in patients receiving parenteral pentamidine.31 52

Hypoglycemia,203 217 219 277 279 hyperglycemia,219 275 and diabetes219 also have occurred in patients receiving pentamidine by oral inhalation via nebulization.

Monitor blood glucose concentrations before, during (daily or every other day), and after IM or IV pentamidine.1 135 169 165 180

Use with caution in patients with hypoglycemia or hyperglycemia.1

Pancreatitis

Acute pancreatitis1 128 166 168 322 335 (sometimes fatal)168 reported with IM or IV pentamidine. Acute pancreatitis also reported rarely in patients receiving pentamidine by oral inhalation via nebulization.219 246 274

Use with caution in patients with pancreatitis.1 Discontinue if acute pancreatitis occurs.166 219

Selection and Use for Treatment or Prevention of Pneumocystis jirovecii Pneumonia

Use IM or IV pentamidine for treatment of PCP only in patients in whom the presence of P. jirovecii has been demonstrated.1

Prior to initiating pentamidine oral inhalation via nebulization for prevention of PCP, evaluate symptomatic patients to rule out P. jirovecii infection.219 Dosage of orally inhaled pentamidine used for prevention of PCP is insufficient for treatment of PCP.219

Patients receiving the drug for prevention of PCP may still develop acute PCP.219 278 Extrapulmonary and/or disseminated P. jirovecii infection also reported occasionally during PCP prophylaxis,200 219 231 236 239 240 249 276 278 usually in patients with a history of PCP.219 236 240 249 276

Monitor patients receiving PCP prophylaxis for signs and symptoms of pulmonary infection (e.g., fever, cough, dyspnea); evaluate those with signs or symptoms to rule out infection caused by P. jirovecii or other opportunistic or nonopportunistic pathogens.219 223 239 247 249 If PCP develops, discontinue prophylaxis and initiate treatment with co-trimoxazole, parenteral pentamidine, or another effective regimen.195 221 223 247 248 PCP prophylaxis can be reinstituted when treatment is complete.221 247

Respiratory Effects

Cough and bronchospasm reported frequently when pentamidine administered by oral inhalation via nebulization,219 231 277 278 279 especially in those with a history of smoking or asthma.174 208 211 212 217 Bronchospasm also reported after parenteral administration.1 210

Cough or bronchospasm in patients receiving pentamidine by oral inhalation can be controlled in most patients by interrupting pentamidine treatment and administering a bronchodilator.193 211 212 219 278 279 Coughing also may be controlled by slowing the delivery or intensity of the pentamidine aerosol stream.193 195 211 212 217

Pretreatment with an orally inhaled bronchodilator may minimize occurrence of coughing and bronchospasm.176 177 193 208 211 212 279 315 316

Sensitivity Reactions

IM or IV: Anaphylaxis,1 anaphylactoid reactions with shock,52 53 Stevens-Johnson syndrome,1 83 and toxic epidermal necrolysis reported.125 Use with caution in patients with Stevens-Johnson syndrome.1 219

Oral inhalation via nebulization: Anaphylaxis, allergic reaction, and nonspecific allergy reported.219

Pruritus,1 83 83 101 210 local or generalized urticaria,1 52 124 167 210 rash1 83 124 167 279 337 (e.g., maculopapular, pruritic)124 337 also reported with IM or IV administration.

Rash,174 193 219 242 including severely pruritic, maculopapular eruption on upper chest and back,242 also reported in patients receiving the drug by oral inhalation via nebulization.1 219 278

Major Toxicities

Renal Effects

IM or IV: Nephrotoxicity (increase in Scr and/or BUN, azotemia, renal insufficiency, renal failure) reported.1 52 83 84 85 86 89 90 96 167 169 188 202 271 279

Oral inhalation via nebulization: Flank pain,219 incontinence,219 increased BUN and Scr,219 nephritis,219 renal failure,219 renal pain,219 and syndrome of inappropriate antidiuretic hormone secretion (SIADH)219 reported rarely.219 244

Monitor renal function (BUN, Scr) before, during (daily or every other day), and after therapy.1 135 165 169 Consider monitoring serum potassium concentrations, particularly in AIDS patients.258 259

Ensure that patients are well hydrated; monitor fluid status.258 259 (See Renal Impairment under Cautions.)

Hepatic Effects

IM or IV: Elevated liver function test results reported.1 83 167 169 174 202

Hepatitis,1 219 hepatomegaly,1 219 and hepatic dysfunction1 219 reported in patients receiving the drug parenterally or by oral inhalation via nebulization.

Monitor hepatic function (serum bilirubin, alkaline phosphatase, AST, ALT) before, during, and after therapy.1 (See Hepatic Impairment under Cautions.)

Hematologic Effects

IM or IV: Leukopenia (e.g., neutropenia)1 188 202 279 and thrombocytopenia,1 83 167 188 202 279 which can be severe (e.g., leukocyte count <1000/mm3, platelet count <20,000/mm3),1 occur occasionally.1 83 188 202 Anemia,1 83 167 167 eosinophilia,1 pancytopenia,1 and prolonged clotting time1 reported rarely.1

Oral inhalation via nebulization: Anemia reported occasionally; eosinophilia, neutropenia, nonspecific cytopenia, pancytopenia, and thrombocytopenia also reported.219

Monitor CBCs and platelet counts.1 Use with caution in patients with leukopenia, thrombocytopenia, or anemia.1 219

General Precautions

Consider that serious adverse effects reported with parenteral pentamidine also may occur when the drug is administered by oral inhalation via nebulization.174 203 219

Laboratory Monitoring

Monitor renal function (BUN, Scr) before, during (daily or every other day), and after IM or IV pentamidine;1 135 165 169 consider monitoring serum potassium concentrations, particularly in AIDS patients.258 259 Also monitor renal function and for hyperkalemia in patients receiving the drug by oral inhalation via nebulization.219 (See Renal Impairment under Cautions.)

Monitor hepatic function (serum bilirubin, alkaline phosphatase, AST, ALT) before, during, and after IM or IV pentamidine.1 Also monitor hepatic function in patients receiving the drug by oral inhalation via nebulization.219 (See Hepatic Impairment under Cautions.)

Monitor blood glucose concentrations before, during (daily or every other day), and after IM or IV pentamidine.1 135 169 165 180 Also monitor for hypoglycemia and hyperglycemia in patients receiving the drug by oral inhalation via nebulization.219

Because hypocalcemia has been reported, monitor serum calcium concentrations before, during, and after IM or IV pentamidine.1 83 167 Also monitor for hypocalcemia in patients receiving the drug by oral inhalation via nebulization.219

Environmental Exposure of Health-care Personnel and Visitors

Potential risks of environmental exposure to aerosolized pentamidine in health-care personnel and visitors or other individuals present when patients are receiving pentamidine by oral inhalation via nebulization not known.205 211 212 247 251 252 261 264 285 378 380 381 Measurable levels of pentamidine can be present in room air when pentamidine is administered by oral inhalation via nebulization.261 294 378 380 381

Adverse effects reported in health-care personnel and others exposed to aerosolized pentamidine in the environment include eye irritation (e.g., conjunctivitis);204 263 perioral and perinasal paresthesia;263 burning sensation of the eyes, nose, and throat;264 sinus irritation;264 shortness of breath;262 264 338 cough;264 tightness of the chest;264 338 acute bronchospasm;262 headache;264 and light-headedness.264

Cough and bronchospasm frequently occur in patients receiving pentamidine by oral inhalation via nebulization;219 231 277 278 279 health-care personnel and other individuals present during administration of the drug may be at risk of exposure to pathogens that can be transmitted when patients cough (e.g., Mycobacterium tuberculosis).250 264 266 285 380

Because of concerns about potential risks of environmental exposure to aerosolized pentamidine and lack of data regarding potential effects of the drug on the fetus or pregnancy,205 247 251 252 261 264 285 294 some clinicians suggest that pregnant women205 261 264 and possibly those planning to become pregnant (e.g., within 8 weeks of potential exposure)264 avoid environmental exposure to aerosolized pentamidine.

Health-care personnel administering aerosolized pentamidine should be familiar with the manufacturer's instructions for use of the nebulizer delivery system; improper use potentially could result in release of substantial amounts of pentamidine into the environment.247 261

Because potential risks, particularly long-term and cumulative effects, associated with environmental exposure to aerosolized pentamidine not established,205 247 251 252 261 264 285 378 380 381 health-care facilities should have procedures to minimize environmental exposure to aerosolized pentamidine.205 251 261 262 264 378 380 381 Consult specialized sources for recommended procedures.211 212 251 261 262 264

Specific Populations

Pregnancy

Category C.1 219

For treatment of first-stage (hemolymphatic) trypanosomiasis or treatment of leishmaniasis in pregnant women, WHO states do not use IM or IV pentamidine during first trimester of pregnancy, but may use after first trimester.44 46

Some clinicians suggest that pregnant women and possibly those planning to become pregnant (e.g., within 8 weeks of potential exposure) avoid environmental exposure to aerosolized pentamidine.205 261 264 (See Environmental Exposure of Health-care Personnel and Visitors under Cautions.)

Lactation

Not known whether distributed into milk.1 219 Discontinue nursing or the drug.1 219

Pediatric Use

IM or IV: Safety and efficacy established for treatment of PCP in children >4 months of age;1 no unusual risks identified.85 89 90 130 Also has been used effectively and apparently without unusual risks in children for treatment of first-stage (hemolymphatic) African trypanosomiasis100 101 and for treatment of leishmaniasis.53

Oral inhalation via nebulization: Manufacturer states safety and efficacy not established in children ≤16 years of age.219 Recommended by CDC, NIH, IDSA, and AAP as an alternative for prevention of PCP in children ≥5 years of age capable of effectively using the Respirgard II jet nebulizer.156

Hepatic Impairment

IM or IV: Use with caution in patients with hepatic impairment;1 219 safety and efficacy of alternative dosage regimens not established in these patients.1

Oral inhalation via nebulization: Pharmacokinetic data not available.219

Renal Impairment

IM or IV: Use with caution in patients with renal impairment;1 safety and efficacy of alternative dosage regimens not established in these patients.1 (See Renal Impairment under Dosage and Administration.)

Oral inhalation via nebulization: Pharmacokinetic data not available.219

Common Adverse Effects

IM or IV: Nephrotoxicity,1 83 84 85 86 89 96 167 169 188 202 271 hypotension,1 41 43 52 83 86 124 159 167 188 202 279 hepatic effects,1 83 167 169 174 202 GI effects (anorexia, nausea, vomiting),1 52 83 90 167 202 219 278 279 hematologic effects (leukopenia),1 188 202 279 hypoglycemia,1 31 32 33 34 35 81 83 84 85 86 89 90 165 167 169 180 188 202 243 injection site reactions.1 81 83 86 124

Oral inhalation via nebulization: Respiratory effects (cough, bronchospasm, wheezing, shortness of breath),219 222 231 278 279 GI effects (diarrhea, nausea, decreased appetite).219

Interactions for Pentamidine Isethionate

Nephrotoxic Drugs

Closely monitor or avoid concurrent or sequential use with other nephrotoxic drugs since nephrotoxic effects may be additive.1 83 84 85 219

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Amphotericin B

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Capreomycin

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Colistin (commercially available in US as colistimethate sodium)

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Cisplatin

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Foscarnet

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Polymyxin B

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Vancomycin

Nephrotoxic effects may be additive1 83 84 85 219

Closely monitor or avoid concurrent or sequential use1 83 84 85 219

Pentamidine Isethionate Pharmacokinetics

Absorption

Bioavailability

Well absorbed following IM administration.1 77

Bronchoalveolar lavage fluid concentrations attained following oral inhalation are substantially higher (at least 5–10 times) than those attained following IV administration.174 181 182 211 212 219 277

Appears to undergo limited absorption from the respiratory tract into systemic circulation,174 181 182 but possible extent of accumulation following chronic oral inhalation therapy not known.219

Plasma Concentrations

Peak plasma concentrations attained following oral inhalation via nebulization are substantially lower than those attained following IV administration.182 219

Special Populations

Plasma pentamidine concentrations following parenteral administration are higher in patients with renal impairment.1 77

Distribution

Extent

Rapidly and extensively distributed and/or bound to tissues.77 171 183 Following parenteral administration, highest concentrations are found in liver, followed by kidneys, adrenals, spleen, lungs, and pancreas in AIDS patients.183

Penetrates the CNS poorly.2 15 43 44 100 101 102 103

Deposition of orally inhaled pentamidine shows considerable interindividual variation; appears to depend on several factors, including delivery device, particle size of aerosolized drug, dose, patient position, and nebulization efficiency.181 182 219 284 293 296

Crosses the placenta;355 not known whether distributed into milk.

Plasma Protein Binding

69%.172

Elimination

Elimination Route

Excreted in urine as unchanged drug;77 171 185 renal clearance accounts for ≤5% of total body clearance.171 172 185

Not appreciably removed by hemodialysis or peritoneal dialysis.185

Half-life

IV: 6.4 hours.1 171

IM: 9.4 hours.1 171

Eliminated very slowly from tissues where the drug accumulates (e.g., liver, lungs);182 183 terminal half-lives of 2.8–12 days reported with IV dosage of 2–4 mg/kg daily.1

Special Populations

Parenteral: Limited data indicate half-life not substantially altered in patients with mild to moderate renal impairment, but may be prolonged up to ≥2 days in those with severe renal impairment.185

Oral inhalation via nebulization: Information not available on pharmacokinetics in patients with renal or hepatic impairment.219

Stability

Storage

Parenteral

Powder for IM or IV Use

20–25°C; protect from light.1

Following reconstitution with sterile water for injection, stable in original vial for 48 hours at room temperature if protected from light.1 Store at 22–30°C to avoid crystallization.1

Following dilution with 5% dextrose in water to a concentration of 1 or 2.5 mg/mL, stable at room temperature for up to 24 hours.1

Oral Inhalation via Nebulization

Powder for Inhalation Solution

20–25°C; protect from light.219

Following reconstitution with sterile water for injection, stable in original vial for 48 hours if protected from light.219

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Y-site CompatibilityHID1

Compatible

Diltiazem HCl

Zidovudine

Incompatible

Aldesleukin

Cefazolin sodium

Cefotaxime sodium

Cefoxitin sodium

Ceftazidime

Ceftriaxone sodium

Fluconazole

Foscarnet sodium

Lansoprazole

Linezolid

Oral Inhalation

Do not mix with other drugs.219

Actions and Spectrum

  • The exact mechanism(s) of antiprotozoal action not fully elucidated;1 2 8 9 10 11 12 13 14 15 16 17 18 19 44 219 interferes with protozoal nuclear metabolism by inhibiting DNA, RNA, phospholipid, and protein synthesis.1 219

  • Spectrum of activity includes many protozoa2 8 9 10 11 12 13 15 22 23 27 41 42 43 44 46 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 80 81 82 83 84 85 86 89 90 96 and some fungi.1 15 28 29 30 79 80 81 82 83 84 85 86 89 90 96

  • Active in vivo and in vitro against P. jirovecii (formerly P. carinii).1 15 28 29 30 79 80 81 82 83 84 85 86 89 90 96 In vitro studies indicate the drug appears to be directly lethal to P. jirovecii at concentrations attainable in vivo.28 29 30

  • Active in vitro and/or in vivo against causative agents of African trypanosomiasis, including most strains of T. b. gambiense2 15 41 42 43 44 146 147 148 and some strains of T. b. rhodesiense;2 15 27 41 42 43 44 59 149 150 151 not active against T. cruzi (causative agent of American trypanosomiasis [Chagas disease]).2 15 59

  • Active in vitro and/or in vivo against L. donovani (including antimony-resistant strains)50 52 53 54 153 and L. aethiopica.46 55 56

  • Resistance to pentamidine has been reported in some trypanosomes;74 75 76 resistance appears to occur primarily because of reduced uptake of the drug.44 74 75 76

Advice to Patients

  • Importance of completing full course of therapy.219

  • When used for the prevention of PCP, importance of informing clinicians if symptoms of a pulmonary infection (cough, fever, dyspnea) occur.219

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 219

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 219

  • Importance of informing patients of other important precautionary information.1 219 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pentamidine Isethionate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

For solution, for nebulization

300 mg

NebuPent

APP

Parenteral

For injection

300 mg*

Pentam 300

APP

Pentamidine Isethionate for Injection

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 29, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. APP Pharmaceuticals, LLC. Pentam 300 (pentamidine isethionate) lyophilized powder, for injection for intramuscular or intravenous use prescribing information. Schaumburg, IL; 2008 Mar.

2. Schoenbach EB, Greenspan EM. The pharmacology, mode of action and therapeutic potentialities of stilbamidine, pentamidine, propamidine and other aromatic diamidines—a review. Medicine (Baltimore). 1948; 27:327-77. [PubMed 18885033]

3. Wien R. The pharmacological actions of certain aromatic diamidines possessing trypanocidal activity. Ann Trop Med Parasit. 1943; 37:1-18.

4. Lourie EM, Yorke W. Studies in chemotherapy. XXI. The trypanocidal action of certain aromatic diamidines. Ann Trop Med Parasit. 1939; 33:289-304.

5. Ashley JN, Barber HJ, Ewins AJ et al. A chemotherapeutic comparison of the trypanocidal action of some aromatic diamidines. J Chem Soc. 1942; 20:103-16.

6. The British pharmacopoeia. London: Her Majesty's Stationery Office; 1980:330.

7. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983:1023.

8. Chesters JK. Protein synthesis by cell-free extracts of Crithidia oncopelti. Biochim Biophys Acta. 1966; 114:385-97.

9. Wallis DC. The effect of pentamidine on ribosomes of the parasitic flagellate Crithidia (Strigomonas) oncopelti. J Protozool. 1966; 13:234-9.

10. Bachrach U, Brem S, Wertman SB et al. Leishmania spp.: effect of inhibitors on growth and on polyamine and macromolecular syntheses. Exp Parasitol. 1979; 48:464-70. [PubMed 510448]

11. Gutteridge WE. Some effects of pentamidine di-isethionate on Crithidia fasciculata. J Protozool. 1969; 16:306-11.

12. Kaplan HG, Myers CE. Complex inhibition of thymidylate synthetase by aromatic diamidines: evidence for both rapid, freely reversible and slowly progressive, nonequilibrium inhibition. J Pharmacol Exp Ther. 1977; 201:554-63. [PubMed 864595]

13. Hill GC, Hutner SH. Effect of trypanocidal drugs on terminal respiration of Crithidia fasciculata. Exp Parasitol. 1968; 22:207-12.

14. Bornstein RS, Yarbro JW. An evaluation of the mechanism of action of pentamidine isethionate. J Surg Oncol. 1970; 2:393-8. [PubMed 5315524]

15. Rollo IM. Miscellaneous drugs used in the treatment of protozoal infections. In: Gilman AG, Goodman L, Goodman A, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 6th ed. New York: Macmillan Publishing Company; 1980:1071-2.

16. Bowman WC, Rand MJ, eds. Chapter 36: Chemotherapy of protozoal infections. In: Textbook of pharmacology. 2nd ed. Oxford: Blackwell Scientific Publications; 1980.

17. Makulu DR, Waalkes TP. Interaction between aromatic diamidines and nucleic acids: possible implications for chemotherapy. J Natl Cancer Inst. 1975; 54:305-9. [PubMed 234535]

18. Festy B, Sturm J, Daune M. Interaction between hydroxystilbamidine and DNA. I. Binding isotherms and thermodynamics of the association. Biochim Biophys Acta. 1975; 407:24-42. [PubMed 1242363]

19. Williamson J. Effects of trypanocides on the fine structure of target organisms. Pharmacol Ther. 1979; 7:445-512. [PubMed 392561]

20. Macadam RF, Williamson J. Drug effects on the fine structure of Trypanosoma rhodesiense: diamidines. Trans R Soc Trop Med Hyg. 1972; 66:897-904. [PubMed 4678907]

21. Hentzer B, Kobayasi T. The ultrastructural changes of Leishmania tropica after treatment with pentamidine. Ann Trop Med Parasitol. 1977; 71:157-66. [PubMed 869606]

22. Croft SL, Brazil RP. Effect of pentamidine isethionate on the ultrastructure and morphology of Leishmania mexicana amazonensis in vitro. Ann Trop Med Parasitol. 1982; 76:37-43. [PubMed 7082077]

23. Langreth SG, Berman JD, Riordan GP et al. Fine-structural alterations in Leishmania tropica within human macrophages exposed to antileishmanial drugs in vitro. J Protozool. 1983; 30:555-61. [PubMed 6315928]

24. Waalkes TP, Makulu DR. Pharmacologic aspects of pentamidine. Natl Cancer Inst Monogr. 1976; 43:171-6. [PubMed 1018718]

27. Steck EA, Kinnamon KE. Leishmania donovani, Plasmodium berghei, Trypanosoma rhodesiense: antiprotozoal effects of some amidine types. Exp Parasitol. 1981; 52:404-13. [PubMed 7032963]

28. Pesanti EL. In vitro effects of antiprotozoan drugs and immune serum on Pneumocystis carinii. J Infect Dis. 1980; 141:775-80.

29. Pesanti EL, Cox C. Metabolic and synthetic activities of Pneumocystis carinii in vitro. Infect Immun. 1981; 34:908-14. [PubMed 6174453]

30. Pifer LL, Pifer DD, Woods DR. Biological profile and response to anti-pneumocystis agents of Pneumocystis carinii in cell culture. Antimicrob Agents Chemother. 1983; 24:674-8. [PubMed 6607029]

31. Bouchard P, Sai P, Reach G et al. Diabetes mellitus following pentamidine-induced hypoglycemia in humans. Diabetes. 1982; 31:40-5. [IDIS 145888] [PubMed 6759211]

32. Klinkhamer LV. Hypoglycaemia during pentamidine treatment for trypanosomiasis. Trop Geogr Med. 1958; 10:332-6. [PubMed 13635851]

33. Fitzgerald DB, Young IS. Reversal of pentamidine-induced hypoglycaemia with oral diazoxide. J Trop Med Hyg. 1984; 87:15-9. [IDIS 191888] [PubMed 6371261]

34. Raia JJ, Patton LR, Klein RA et al. Prolonged hypoglycemia during pentamidine therapy. Clin Pharm. 1983; 2:505-6. [IDIS 178532] [PubMed 6653049]

35. Jha TK, Sharma VK. Pentamidine-induced diabetes mellitus. Trans R Soc Trop Med Hyg. 1984; 78:252-3. [IDIS 191886] [PubMed 6464116]

36. Sai P, Boillot D, Boitard C et al. Pentamidine, a new diabetogenic drug in laboratory rodents. Diabetologia. 1983; 25:418-23. [PubMed 6360780]

37. Osei K, Falko JM, Nelson KP et al. Diabetogenic effect of pentamidine: in vitro and in vivo studies in a patient with malignant insulinoma. Am J Med. 1984; 77:41-6. [IDIS 187519] [PubMed 6331162]

38. Bielenberg VGW, Krieglstein J. Uber die blutdrucksenkende Wirkung aromatischer Amidine und Imidazoline. (German; with English abstract) Arzneim-Forsch. 1984; 34:958-67.

39. Macintosh FC, Paton WDM. The liberation of histamine by certain organic bases. J Physiol. 1949; 109:190-219. [PubMed 15394320]

40. Kempin SJ, Jackson CW, Edwards CC. In vitro inhibition of platelet function and coagulation by pentamidine isethionate. Antimicrob Agents Chemother. 1977; 12:451-4. [IDIS 93656] [PubMed 921238]

41. Spencer HC. African trypanosomiasis. In: Strickland GT, ed. Hunter's tropical medicine. 6th ed. Philadelphia: WB Saunders; 1984: 553-64.

42. Kirchhoff LV. Agents of African trypanosomiasis (sleeping sickness). In: Mandell GL, Bennett, JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 5th ed. Philadelphia, PA: Churchill Livingston; 2000:2853-8.

43. Apted FIC. Treatment of human trypanosomiasis. In: Mulligan H, Potts WH, eds. The African trypanosomiases. London: George Allen & Unwin; 1970:684-710.

44. World Health Organization. Control and surveillance of human African trypanosomiasis: report of a WHO Expert Committee. Technical Report Series No. 984. Geneva: World Health Organization; 2013.

46. World Health Organization. Control of leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniasis, Geneva, 22–26 March 2010. Who Technical Report Series No. 949. Geneva: World Health Organization; 2010.

48. Collier HOJ, Lourie EM. The action in vitro of diamidines and other compounds on Leishmania donovani. Ann Trop Med Parasitol. 1946; 40:88-100.

49. Berman JD, Wyler DJ. An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. J Infect Dis. 1980; 142:83-6. [PubMed 6249874]

50. Berman JD. In vitro susceptibility of antimony-resistant Leishmania to alternative drugs. J Infect Dis. 1982; 145:279. [IDIS 146093] [PubMed 6274970]

51. Berman JD, Lee LS. Activity of antileishmanial agents against amastigotes in human monocyte-derived macrophages and in mouse peritoneal macrophages. J Parasitol. 1984; 70:220-5. [PubMed 6088749]

52. Jha TK. Evaluation of diamidine compound (pentamidine isethionate) in the treatment of resistant cases of kala-azar occurring in North Bihar, India. Trans R Soc Trop Med Hyg. 1983; 77:167-70. [IDIS 191889] [PubMed 6868096]

53. Thakur CP. Epidemiological, clinical and therapeutic features of Bihar kala-azar (including post kala-azar dermal leishmaniasis). Trans R Soc Trop Med Hyg. 1984; 78:391-8. [IDIS 191887] [PubMed 6087515]

54. Thakur CP, Kumar M, Singh SK et al. Comparisons of regimens of treatment with sodium stibogluconate in kala-azar. BMJ. 1984; 288:895-7. [IDIS 184013] [PubMed 6322906]

55. Zaar K, Wunderlich F. Electron microscopical studies on cutaneous leishmaniasis in Ethiopia. I. The diffuse form and its treatment with pentamidine. Ann Trop Med Parasitol. 1982; 76:595-605. [IDIS 191902] [PubMed 7171248]

56. Bryceson ADM. Diffuse cutaneous leishmaniasis in Ethiopia. II. Treatment. Trans R Soc Trop Med Hyg. 1970; 64:369-79. [PubMed 5453496]

57. Low-a-chee RM, Rose P, Ridley DS. An outbreak of cutaneous leishmaniasis in Guyana: epidemiology, clinical and laboratory aspects. Ann Trop Med Parasitol. 1983; 77:255-60. [PubMed 6625725]

58. Chulay JD. Cutaneous leishmaniasis of the new world. In: Strickland GT, ed. Hunter's tropical medicine. 6th ed. Philadelphia: WB Saunders; 1984:589-93.

59. Lourie EM, Yorke W. Studies in chemotherapy. XXI. The trypanocidal action of certain aromatic diamidines. Ann Trop Med Hyg. 1939; 33:289-304.

60. Adler S, Tchernomoretz I, Ber M. The action of some aromatic diamidines on cultures of Leishmania donovani. Ann Trop Med Parasitol. 1945; 39:14-9.

61. Lourie EM, Yorke W. Studies in chemotherapy. XXII. The action of certain aromatic diamidines on Babesia canis infections of puppies. Ann Trop Med Parasitol. 1939; 33:305-12.

62. Miller LH, Neva FA, Gill F. Failure of chloroquine in human babesiosis (Babesia microti): case report and chemotherapeutic trials in hamsters. Ann Intern Med. 1978; 88:200-2. [IDIS 77374] [PubMed 626449]

63. Ruebush TK II, Contacos PG, Steck EA. Chemotherapy of Babesia microti infections in Mongolian jirds. Antimicrob Agents Chemother. 1980; 18:289-91. [PubMed 7447406]

64. Stenderup A. Effect of diamidines on Candida albicans in vitro. Acta Pathol Microbiol Scand. 1955; 36:361-4. [PubMed 14387697]

65. Fahlberg WJ. A comparison of fungistatic properties of three aromatic diamidines. Proc Soc Exp Biol Med. 1953; 84:84-7. [PubMed 13120942]

66. Stenderup A, Bichel J, Kissmeyer-Nielsen F. Moniliasis treated with pentamidine. Lancet. 1956; 1:20-1.

67. Bocobo FC, Curtis AC, Harrell ER. In vitro fungistatic activity of stilbamidine, propamidine, pentamidine and diethylstilbestrol. J Invest Dermatol. 1953; 21:149-56. [PubMed 13084980]

68. Christison IB, Conant NF. Antifungal activity of some aromatic diamidines. J Lab Clin Med. 1953; 42:638-40. [PubMed 13096901]

69. Bichowsky-Slomnitzki L. The effect of aromatic diamidines on bacterial growth. I. The mechanism of action. J Bacteriol. 1948; 55:27-31.

70. Amos H, Vollmayer E. Effect of pentamidine on the growth of Escherichia coli. J Bacteriol. 1957; 73:172-7.

71. Eaton MD, Perry ME, Levenson CG et al. Studies on the mode of action of aromatic diamidines on influenza and mumps virus in tissue culture. J Immunol. 1952; 68:321-34. [PubMed 14938548]

72. Williamson J. Review of chemotherapeutic and chemoprophylactic agents. In: Mulligan H, Potts WH, eds. The African trypanosomiases. London: George Allen & Unwin; 1970:125-221.

73. Williamson J. Drug resistance in trypanosomes: effects of metabolic inhibitors, pH and oxidation-reduction potential on normal and resistant Trypanosoma rhodesiense. Bur J Pharmacol. 1959; 14:443-55.

74. Damper D, Patton CL. Pentamidine transport and sensitivity in brucei-group trypanosomes. J Protozool. 1976; 23:349-56. [PubMed 6797]

75. Damper D, Patton CL. Pentamidine transport in Trypanosoma brucei—kinetics and specificity. Biochem Pharmacol. 1976; 25:271-6. [PubMed 1267824]

76. Wallis OC. Pentamidine resistance in the parasitic flagellate Crithidia (Strigomonas) oncopelti. J Protozool. 1966; 13:230-4.

77. Waalkes TP, Denham C, DeVita VT. Pentamidine: clinical pharmacologic correlations in man and mice. Clin Pharmacol Ther. 1970; 11:505-12. [IDIS 15141] [PubMed 5310706]

78. Waldman RH, Pearce DE, Martin RA. Pentamidine isethionate levels in lungs, livers, and kidneys of rats after aerosol or intramuscular administration. Am Rev Respir Dis. 1973; 108:1004-6. [PubMed 4355009]

79. Food and Drug Administration. List of orphan designations and approvals. From FDA web site.

80. Robbins JB. Pneumocystis carinii pneumonitis: a review. Pediatr Res. 1967; 1:131-58. [PubMed 5339830]

81. Burke BA, Good RA. Pneumocystis carinii infection. Medicine (Baltimore). 1973; 52:23-51. [PubMed 4540153]

82. Goodell B, Jacobs JB, Powell RD et al. Pneumocystis carinii: the spectrum of diffuse interstitial pneumonia in patients with neoplastic diseases. Ann Intern Med. 1970; 72:337-40. [PubMed 5308994]

83. Western KA, Perera DR, Schultz MG. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Ann Intern Med. 1970; 73:695-702. [IDIS 17454] [PubMed 5312203]

84. Walzer PD, Perl DP, Krogstad DJ et al. Pneumocystis carinii pneumonia in the United States: epidemiologic, diagnostic, and clinical features. Ann Intern Med. 1974; 80:83-93. [IDIS 191892] [PubMed 4589515]

85. Hughes WT, Price RA, Kim HK et al. Pneumocystis carinii pneumonitis in children with malignancies. J Pediatr. 1973; 82:404-15. [PubMed 4572932]

86. Lipson A, Marshall WC, Hayward AR. Treatment of Pneumocystis carinii pneumonia in children. Arch Dis Child. 1977; 52:314-9. [IDIS 85385] [PubMed 301010]

89. Hughes WT, Feldman S, Chaudhary SC et al. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. J Pediatr. 1978; 92:285-91. [IDIS 102397] [PubMed 304478]

90. Siegel SE, Wolff LJ, Baehner RL et al. Treatment of Pneumocystis carinii pneumonitis. A comparative trial of sulfamethoxazole-trimethoprim v pentamidine in pediatric patients with cancer: report from the Children's Cancer Study Group. Am J Dis Child. 1984; 138:1051-4. [IDIS 192144] [PubMed 6388315]

96. Kovacs JA, Hiemenz JW, Macher AM et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984; 100:663-71. [PubMed 6231873]

100. Lawson TL. Trypanosomiasis treated with ″pentamidine'. Lancet. 1942; 2:480-3.

101. Lourie EM. Treatment of sleeping sickness in Sierra Leone. Ann Trop Med Parasitol. 1942; 36:113-31.

102. Harding RD. Trypanosomiasis treated with pentamidine. Br Med J. 1944; 2:447.

103. Van Hoof L, Henrard C, Peel E. Pentamidine in the prevention and treatment of trypanosomiasis. Trans R Soc Trop Med Hyg. 1944; 37:271-80.

104. Van Hoof L, Lewillon R, Henrard C et al. A field experiment on the prophylactic value of pentamidine in sleeping sickness. Trans Roy Soc Trop Med Hyg. 1946: 39:327-9.

105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

107. Molyneux DH. Selective primary health care: strategies for control of disease in the developing world. VIII. African trypanosomiasis. Rev Infect Dis. 1983; 5:945-56. [IDIS 176530] [PubMed 6635428]

113. Chulay JD, Manson-Bahr PEC. Visceral leishmaniasis (kala-azar). In: Strickland GT, ed. Hunter's tropical medicine. 6th ed. Philadelphia: WB Sauders Company; 1984:578-85.

114. Chulay JD, Manson-Bahr PEC. Cutaneous leishmaniasis of the old world. In: Strickland GT, ed. Hunter's tropical medicine. 6th ed. Philadelphia: WB Sauders Company; 1984:585-9.

115. Francioloi PB, Keithly JS, Jones TC et al. Response of babesiosis to pentamidine therapy. Ann Intern Med. 1981; 94:326-30. [IDIS 128945] [PubMed 7194615]

116. Ortiz JM, Eagle RC Jr. Ocular findings in human babesiosis (Nantucket fever). Am J Ophthalmol. 1982; 93:307-11. [IDIS 146816] [PubMed 7200325]

117. Jacoby GA, Hunt JV, Kosinski KS et al. Treatment of transfusion-transmitted babesiosis by exchange transfusion. N Engl J Med. 1980; 303:1098-1100. [IDIS 123360] [PubMed 7191475]

118. Teutsch SM, Etkind P, Burwell EL et al. Babesiosis in post-splenectomy hosts. Am J Trop Med Hyg. 1980; 29:738-41. [IDIS 191904] [PubMed 7192058]

119. Gombert ME, Goldstein EJC, Benach JL et al. Human babesiosis: clinical and therapeutic considerations. JAMA. 1982; 248:3005-7. [IDIS 161440] [PubMed 6890585]

120. Teutsch SM, Juranek DD. Babesiosis. Ann Intern Med. 1981; 95:241.

124. Navin TR, Fontaine RE. Intravenous versus intramuscular administration of pentamidine. N Engl J Med. 1984; 311:1701-2. [IDIS 194109] [PubMed 6504113]

125. Wang JJ, Freeman AI, Gaeta JF et al. Unusual complications of pentamidine in the treatment of Pneumocystis carinii pneumonia. J Pediatr. 1970; 77:311-4. [IDIS 13410] [PubMed 5310885]

126. Pearson RD, De Queiroz Sousa A, Jeronimo SMB. Leishmania species: visceral (kala-azar), cutaneous, and mucosal leishmaniasis. In: Mandell GL, Bennett, JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 5th ed. Philadelphia, PA: Churchill Livingston; 2000:2831-44.

127. Levy MA, Senior RM, Sneider RE. Severe thrombocytopenic purpura complicating pentamidine therapy for Pneumocystis carinii pneumonia. Cancer. 1974; 34:441-3. [IDIS 44565] [PubMed 4546914]

128. Murphey SA, Josephs AS. Acute pancreatitis associated with pentamidine therapy. Arch Intern Med. 1981; 141:56-8. [IDIS 129855] [PubMed 6969581]

130. Ivady G, Paldy L. Treatment of Pneumocystis carinii pneumonia in infancy. Natl Cancer Inst Monogr. 1976; 43:201-8. [IDIS 191895] [PubMed 1087956]

134. Anon. Drugs for parasitic infections. Treat Guidel Med Lett. 2010; 8:e1-16.

135. Reviewers' comments (personal observations).

136. Hazarika AN. Treatment of kala-azar with pentamidine isothionate: a study of 55 cases. Indian Med Gaz. 1949; 84:140-5.

137. Sen Gupta PC. The treatment of kala-azar and its complications. J Indian Med Assoc. 1949; 18:377-82.

138. Lee TM, Ling CC. Preliminary observations on the treatment of Chinese kala-azar with pentamidine isothionate. Chin Med J (Peking, 1932–1966). 1951; 69:160-70.

141. Wien R, Freeman W, Scotcher NM. The metabolic effects produced by certain aromatic diamidines. Ann Trop Med Parasitol. 1943; 37:19-33.

142. Goble FC, Hoppe JO. Observations on the toxicity of certain trypanocidal quinaldines and aromatic diamidines. Antibiot Chemother (Washington, DC). 1952; 2:581-9.

144. Fulton JD. The course of Plasmodium relictum infection in canaries and the treatment of bird and monkey malaria with synthetic bases. Ann Trop Med Parasitol. 1940; 34:53-66.

146. Gilbert FW. Preliminary report on pentamidine in the treatment of late cases of sleeping sickness. Trans R Soc Trop Med Hyg. 1943; 36:353-8.

147. Harding RD, Hutchinson MP. Mass prophylaxis against sleeping sickness in Sierra Leone: final report. Trans R Soc Trop Med Hyg. 1950; 43:503-12.

148. Jonchère H. Chimioprophylaxie de la trypanosomiase humaine en A.O.F. Bull Soc Pathol Exot Ses Fil. 1951; 44:83-93.

149. Gelfand M, Alves WD. Three early cases of Rhodesian sleeping sickness treated with pentamidine isethionate. Trans R Soc Trop Med Hyg. 1954; 48:146-9. [PubMed 13157160]

150. de Andrade Silva MA. The value of drugs commonly used in the treatment of T. rhodesiense sleeping sickness. An Inst Med Trop Lisbon. 1957; 14:159-70. [PubMed 13521347]

151. de Andrade Silva MA, Caseiro A. Prophylactic action of diamidines against T. rhodesiense infection. An Inst Med Trop Lisbon. 1957; 14:171-7. [PubMed 13521348]

152. Fendall NRE. Kala-azar in East Africa with particular reference to Kenya and the Kamba country. Part IV. Clinical studies. J Trop Med Hyg. 1952; 50:245-56.

153. Prasad KM, Singh BP, Nevatia SK et al. Re-emergence of kala-azar and resistance to drugs. Arch Child Health. 1979; 21(2):29-35.

154. Correa A, da Rocha Brito G. Traitement de la leishmaniose muqueuse Sud-Américaine par la diamidinophenoxypentane. Bull Soc Pathol Exot Ses Fil. 1954; 47:513-7.

155. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (May 7, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

156. Panel on Opportunistic Infection in HIV-exposed and HIV-infected children, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (Nov 6, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

158. Stehr-Green JK, Helmick CG. Pentamidine and renal toxicity. N Engl J Med. 1985; 313:694-5. [IDIS 204306] [PubMed 4022063]

159. Helmick CG, Green JK. Pentamidine-associated hypotension and route of administration. Ann Intern Med. 1985; 103:480. [IDIS 205833] [PubMed 4026103]

162. De NC, Alam AS, Kapoor JN. Stability of pentamidine isethionate in 5% dextrose and 0.9% sodium chloride injections. Am J Hosp Pharm. 1986; 43:1486-8. [PubMed 3728484]

163. Sensakovic JW, Saurez M, Perez G et al. Pentamidine treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: association with acute renal failure and myoglobinuria. Arch Intern Med. 1985; 145:2247. [IDIS 208401] [PubMed 3878136]

164. Shuster M, Dunn M. Pentamidine and hematuria. Ann Intern Med. 1986; 105:146. [IDIS 217867] [PubMed 3487266]

165. Stahl-Bayliss CM, Kalman CM, Laskin OL. Pentamidine-induced hypoglycemia in patients with acquired immune deficiency syndrome. Clin Pharmacol Ther. 1986; 39:271-5. [IDIS 213984] [PubMed 3485027]

166. Salmeron S, Petitpretz P, Katlama C et al. Pentamidine and pancreatitis. Ann Intern Med. 1986; 105:140-1. [IDIS 217861] [PubMed 3487265]

167. Wharton JM, Coleman DL, Wofsy CB et al. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective randomized trial. Ann Intern Med. 1986; 105:37-44. [IDIS 217841] [PubMed 3521428]

168. Zuger A, Wolf BZ, El-Sadr W et al. Pentamidine-associated fatal acute pancreatitis. JAMA. 1986; 256:2383-5. [IDIS 222552] [PubMed 3490588]

169. Andersen R, Boedicker M, Ma M et al. Adverse reactions associated with pentamidine isethionate in AIDS patients: recommendations for monitoring therapy. Drug Intell Clin Pharm. 1986; 20:862-8. [IDIS 222524] [PubMed 3490958]

170. Yurdakok M. Diabetogenic effect of pentamidine. JAMA. 1987; 257:1177. [PubMed 3543425]

171. Conte JE Jr, Upton RA, Phelps RT et al. Use of a specific and sensitive assay to determine pentamidine pharmacokinetics in patients with AIDS. J Infect Dis. 1986; 154:923-9. [IDIS 224946] [PubMed 3491164]

172. Navin TR, Dickinson CM, Adams SR et al. Effect of azotemia in dogs on the pharmacokinetics of pentamidine. J Infect Dis. 1987; 155:1020-6. [PubMed 3559276]

174. Conte JE Jr, Hollander H, Golden JA. Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia: a pilot study. Ann Intern Med. 1987; 107:495-8. [IDIS 234487] [PubMed 3498418]

175. Wharton JM, Demopoulos PA, Goldschlager N. Torsade de pointes during administration of pentamidine isethionate. Am J Med. 1987; 83:571-6. [IDIS 234172] [PubMed 3499072]

176. Montgomery AB, Debs RJ, Luce JM et al. Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet. 1987; 2:480-3. [IDIS 233332] [PubMed 2887779]

177. Jesuthasan AJ, Datta AK, Hamilton R et al. Aerosolised pentamidine. Lancet. 1987; 2:971-2. [IDIS 234824] [PubMed 2889891]

178. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43:1089-134. [PubMed 17029130]

179. Paton WDM. Aerosolised pentamidine. Lancet. 1987; 2:1146.

180. Sattler FR, Waskin H. Pentamidine and fatal hypoglycemia. Ann Intern Med. 1987; 107:789-90. [IDIS 235766] [PubMed 3662308]

181. Montgomery AB, Debs RJ, Luce JM et al. Selective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis. 1988; 137:477-8. [IDIS 314487] [PubMed 3257663]

182. Conte JE Jr, Golden JA. Concentrations of aeosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion. Antimicrob Agents Chemother. 1988; 32:1490-3. [IDIS 246899] [PubMed 3263832]

183. Donnelly H, Bernard EM, Rothkotter H et al. Distribution of pentamidine in patients with AIDS. J Infect Dis. 1988; 157:985-9. [IDIS 242791] [PubMed 3258901]

184. Dusci LJ, Hackett LP, Forbes AM et al. High-performance liquid chromatographic method for measurement of pentamidine in plasma and its application in an immunosuppressed patient with renal dysfunction. Ther Drug Monit. 1987; 9:422-5. [IDIS 243012] [PubMed 3501181]

185. Conte JE Jr, Upton RA, Lin ET. Pentamidine pharmacokinetics in patients with AIDS with impaired renal function. J Infect Dis. 1987; 156:885-90. [IDIS 243322] [PubMed 3680992]

187. Kovacs JA, Masur H. Pneumocystis carinii pneumonia: therapy and prophylaxis. J Infect Dis. 1988; 158:254-9. [IDIS 244493] [PubMed 2969023]

188. Sattler FR, Cowan R, Nielsen DM et al. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a prospective, noncrossover study. Ann Intern Med. 1988; 109:280-7. [IDIS 244954] [PubMed 3260759]

190. Godfrey-Faussett P, Miller RF, Semple SJ. Nebulised pentamidine. Lancet. 1988; 1:645-6. [IDIS 240201] [PubMed 2894573]

191. Girard PM, Couderc LJ, Farinotti R et al. Ultrasonic nebulised pentamidine for pneumocystis pneumonia. Lancet. 1988; 1:1165. [IDIS 242006] [PubMed 2896982]

192. Havlichek D. Aerosolized pentamidine therapy. Ann Intern Med. 1988; 109:167-8. [IDIS 244167] [PubMed 3260086]

193. Corkery KJ, Luce JM, Montgomery AB. Aerosolized pentamidine for treatment and prophylaxis of Pneumocystis carinii pneumonia: an update. Respir Care. 1988; 33:676-85.

194. Raviglione MC, Garner GR, Mullen MP. Pneumocystis carinii in bone marrow. Ann Intern Med. 1988; 109:253. [PubMed 3260460]

195. Armstrong D, Bernard E. Aerosol pentamidine. Ann Intern Med. 1988; 109:852-4. [IDIS 248223] [PubMed 3056163]

198. Merz B. Aerosolized pentamidine promising in Pneumocystis therapy, prophylaxis. JAMA. 1988; 259:3223-4. [PubMed 3259636]

199. Fishman JA. Treatment of infection due to Pneumocystis carinii Antimicrob Agents Chemother. 1998; 42:1309-14.

200. Abd AG, Nierman DM, Ilowite JS et al. Bilateral upper lobe Pneumocystis carinii pneumonia in a patient receiving inhaled pentamidine prophylaxis. Chest. 1988; 94:329-31. [IDIS 244715] [PubMed 3260848]

201. Pujol M, Carratala J, Mauri J et al. Ventricular tachycardia due to pentamidine isethionate. Am J Med. 1988; 84:980. [IDIS 241210] [PubMed 3364459]

202. Waskin H, Stehr-Green JK, Helmick CG et al. Risk factors for hypoglycemia associated with pentamidine therapy for Pneumocystis pneumonia. JAMA. 1988; 260:345-7. [IDIS 243308] [PubMed 3259989]

203. Karboski JA, Godley PJ. Inhaled pentamidine and hypoglycemia. Ann Intern Med. 1988; 108:490. [IDIS 239636] [PubMed 3341691]

204. Lindley DA, Schleupner CJ. Aerosolized pentamidine and conjunctivitis. Ann Intern Med. 1988; 109:988. [IDIS 248617] [PubMed 3195880]

205. Conover B, Goldsmith JC, Buehler BA et al. Aerosolized pentamidine and pregnancy. Ann Intern Med. 1988; 109:927. [IDIS 248226] [PubMed 3190049]

207. Bryceson A. Pentamidine: which salt? Lancet. 1988; 1:1395. Letter.

208. Smith DE, Herd D, Gazzard BG. Reversible bronchoconstriction with nebulised pentamidine. Lancet. 1988; 2:905. [IDIS 247039] [PubMed 2902344]

209. Alston TA. Inhibition of cholinesterases by pentamidine. Lancet. 1988; 2:1423. [IDIS 249117] [PubMed 2904548]

210. Greenberger PA, Patterson R. Management of drug allergy in patients with acquired immunodeficiency syndrome. J Allergy Clin Immunol. 1987; 79:484-8. [IDIS 227033] [PubMed 3819229]

211. Respiratory Care Service, San Francisco General Hospital. Guidelines for aerosolization of pentamidine. San Francisco; 1988 Oct.

212. Respiratory Care Service, San Francisco General Hospital. Guidelines for aerosolization of pentamidine for PCP prophylaxis. San Francisco; 1988 Oct.

215. Martinez CM, Romanelli A, Mullen MP et al. Spontaneous pneumothoraces in AIDS patients receiving aerosolized pentamidine. Chest. 1988; 94:1317-8. [IDIS 310754] [PubMed 3263913]

216. LyphoMed, Inc. A treatment IND for the use of aerosolized pentamidine in HIV-infected individuals at high risk for Pneumocystis carinii pneumonia. Rosemont, IL (undated).

217. LyphoMed, Inc. Clinical investigator's brochure for aerosolized pentamidine treatment IND #32,642. Rosemont, IL; 1989 Jan 31.

219. APP Pharmaceuticals, LLC. NubuPent (pentamidine isethionate) for oral inhalation prescribing information. Schaumburg, IL; 2010 Dec.

221. Kovacs JA, Masur H. Prophylaxis of Pneumocystis carinii pneumonia: an update. J Infect Dis. 1989; 160:882-6. [IDIS 307861] [PubMed 2681438]

222. Girard PM, Landman R, Gaudebout C et al. Prevention of pneumocystis carinii pneumonia relapse by pentamidine aerosol in zidovudine-treated AIDS patients. Lancet. 1989; 1:1348-53. [IDIS 256674] [PubMed 2567372]

223. Luce JM, Hopewell PC. Aerosolized pentamidine for Pneumocystis carinii pneumonia. Chest. 1989; 96:713-4. [IDIS 305758] [PubMed 2791660]

224. Montgomery AB, Debs RJ, Luce JM et al. Aerosolized pentamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia. Chest. 1989; 95:747-50. [IDIS 305623] [PubMed 2784371]

225. Miller RF, Godfrey-Faussett P, Semple SJG. Nebulized pentamidine as treatment for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Thorax. 1989; 44:565-9. [PubMed 2788936]

226. Goto H, Oka S, Mohri H et al. Two cases of Pneumocystis carinii pneumonia occurred in human immunodeficiency virus infected patients: supplemental treatment with aerosolized pentamidine isethionate. Jpn J Med. 1989; 28:105-9. [PubMed 2786100]

231. LyphoMed, Inc. NebuPent (pentamidine isethionate) for inhalation solution product monograph (NebuPent-004). Rosemont, IL; 1989 Jun.

234. Anon. Choosing a nebulizer for pentamidine delivery. Am J Hosp Pharm. 1989; 46:1210.

236. Hardy WD, Northfelt DW, Drake TA. Fatal, disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine. Am J Med. 1989; 87:329-31. [IDIS 258426] [PubMed 2788999]

237. Leoung GS, Montgomery AB, Abrams DJ et al. Aerosol pentamidine for Pneumocystis carinii pneumonia prophylaxis: a 3 arm randomized trial. Fifth International Conference on AIDS. Montreal; 1989:196. Abstract T.B.0.3.

239. Sparling TG, Dong SR, Hegedus C et al. Aerosolized pentamidine and disseminated infection with Pneumocystis carinii. Ann Intern Med. 1989; 111:442. [IDIS 258650] [PubMed 2788380]

240. Hagopian WA, Huseby JS. Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulmonary prophylaxis. Chest. 1989; 4:949-51.

241. Bradburne RM, Ettensohn DB, Opal SM et al. Relapse of Pneumocystis carinii pneumonia in the upper lobes during aerosol pentamidine prophylaxis. Thorax. 1989; 44:591-3. [PubMed 2788937]

242. Berger TG, Tappero JW, Leoung GS et al. Aerosolized pentamidine and cutaneous eruptions. Ann Intern Med. 1989; 110:1035-6. [IDIS 255913] [PubMed 2524983]

243. Lingenfelser T, Glück T, Scheurlen M et al. Pentamidine and hypoglycaemia. Lancet. 1989; 2:458. [IDIS 258090] [PubMed 2569646]

244. Miller RF, Delany S, Semple SJG. Acute renal failure after nebulised pentamidine. Lancet. 1989; 1:1271-2.

245. Miller RF, Semple SJG. Bronchial bleeding with nebulised pentamidine. Lancet. 1988; 2:1488.

246. Hart CC. Aerosolized pentamidine and pancreatitis. Ann Intern Med. 1989; 111:691. [IDIS 259891] [PubMed 2802428]

247. Young FE, Nightingale SL, Cooper EC et al. Aerosolized pentamidine: approved for HIV-infected individuals at high risk for Pneumocystis carinii pneumonia. Arch Intern Med. 1989; 149:2412-3. [IDIS 260608] [PubMed 2818104]

248. Pierone G, Turett G, Masci JR et al. Inhaled pentamidine in pneumocystis carinii pneumonia. Lancet. 1989; 2:559. [IDIS 258659] [PubMed 2570253]

249. Poblete RB, Rodriguez K, Foust RT et al. Pneumocystis carinii hepatitis in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1989; 110:737-8. [IDIS 254416] [PubMed 2784649]

250. Anon. Mycobacterium tuberculosis transmission in a health clinic—Florida, 1988. MMWR Morb Mortal Wkly Rep. 1989; 38:256-7, 263-4. [PubMed 2495425]

251. Gude JK. Selective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis. 1989; 139:1060. [IDIS 252763] [PubMed 2784644]

252. McDiarmid MA, Jacobson-Kram D. Aerosolised pentamidine and public health. Lancet. 1989; 2:863-4. [IDIS 259598] [PubMed 2571783]

253. Masur H, Lane HC, Kovacs JA et al. Pneumocystis pneumonia: from bench to clinic. Ann Intern Med. 1989; 111:813-26. [IDIS 261003] [PubMed 2683916]

255. LyphoMed, Inc. Administering NebuPent (pentamidine isethionate) with the Respirgard II nebulizer system (product information). Rosemont, IL; 1989 Jun.

256. Berman JD. Human leishmaniasis: clinical, diagnostic, and chemotherapeutic development in the last 10 years. Clin Infect Dis. 1997; 24:684-703. [IDIS 384365] [PubMed 9145744]

257. Goldfarb J. Intravenous saline as adjunctive therapy for patients with AIDS given pentamidine. N Engl J Med. 1989; 320:1281. [IDIS 254312] [PubMed 2785244]

258. Lachaal M, Venuto RC. Nephrotoxicity and hyperkalemia in patients with acquired immunodeficiency syndrome treated with pentamidine. Am J Med. 1989; 87:260-3. [IDIS 258417] [PubMed 2773964]

259. Peltz S, Hashmi S. Pentamidine-induced severe hyperkalemia. Am J Med. 1989; 87:698-9. [IDIS 261830] [PubMed 2589407]

261. Montgomery AB, Corkery KJ, Brunette ER et al. Occupational exposure to aerosolized pentamidine. Chest. 1990; 98:386-8. [PubMed 2376170]

262. Doll DC. Aerosolised pentamidine. Lancet. 1989; 2:1284-5. [IDIS 261381] [PubMed 2573803]

263. Thomas SHL, Page CM, O'Doherty MJ et al. Aerosolised pentamidine. Lancet. 1989; 2:1284. [IDIS 261381] [PubMed 2573803]

264. Kacmarek RM. Ribavirin and pentamidine aerosols: caregiver beware! Respir Care. 1990; 35:1034-6.

265. Blumenfeld W, Basgoz N, Owen WF Jr et al. Granulomatous pulmonary lesions in patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii infection. Ann Intern Med. 1988; 109:505-7. [PubMed 3261957]

266. Young FE, Norris JA, Levitt JA et al. The FDA's new procedures for the use of investigational drugs in treatment. JAMA. 1988; 260:224-5. [PubMed 2838651]

267. Nightingale SL. From the Food and Drug Administration. JAMA. 1988; 259:2064.

268. Anon. Treatment IND for AIDS drug. FDA Drug Bull. 1988; 18:2.

271. Buff DD, Aboal AA. Pentamidine-associated renal dysfunction and hyperkalemia. Am J Med. 1990; 88:552. [IDIS 266349] [PubMed 2337115]

272. Marino PL. Pentamidine and hyperkalemia revisited. Am J Med. 1990; 89:397. [IDIS 271039] [PubMed 2393048]

273. Peltz S, Hashmi S. Pentamidine and hyperkalemia revisited. Am J Med. 1990; 89:397-8. [IDIS 271039] [PubMed 2393048]

274. Murphy RL, Noskin FA, Ehrenpreis ED. Acute pancreatitis associated with aerosolized pentamidine. Am J Med. 1990; 88(Suppl 5):5-53-6N.

275. Fisch A, Prazuck T, Malkin JE et al. Diabetes mellitus in a patient with AIDS after treatment with pentamidine aerosol. Br Med J. 1990; 301:875.

276. Sneed SR, Blodi CF, Berger BB et al. Pneumocystis carinii choroiditis in patients receiving inhaled pentamidine. N Engl J Med. 1990; 322:936-7. [IDIS 264362] [PubMed 2314433]

277. Conte JE Jr, Chernoff D, Feigal DW Jr et al. Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS: a randomized trial. Arch Intern Med. 1990; 113:203-9.

278. Leoung GS, Feigal DW Jr, Montgomery AB et al. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia: the San Francisco community prophylaxis trial. N Engl J Med. 1990; 323:769-75. [IDIS 270539] [PubMed 1975426]

279. Soo Hoo GW, Mohsenifar Z, Meyer RD. Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia in AIDS: a randomized trial. Arch Intern Med. . 1990; 113:195-202.

280. Duma RJ, Finley R. In vitro susceptibility of pathogenic Naegleria and Acanthamoeba species to a variety of therapeutic agents. Antimicrob Agents Chemother. 1976; 10:370-6. [IDIS 66432] [PubMed 984777]

281. Jules-Elysee KM, Stover DM, Zaman MB et al. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med. 1990; 112:750-7. [IDIS 265985] [PubMed 2331119]

282. Raoult D, Soulayrol L, Toga B et al. Babesiosis, pentamidine, and cotrimoxazole. Ann Intern Med. 1987; 107:944. [IDIS 237481] [PubMed 3500663]

284. Baskin MI, Abd AG, Ilowite JS. Regional disposition of aerosolized pentamidine: effects of body position and breathing pattern. Ann Intern Med. 1990; 113:677-83. [IDIS 273232] [PubMed 2221648]

285. Diagnostic and Therapeutic Technology Assessment (DATTA) panel. Prophylactic treatment for opportunistic infections in HIV-positive patients: aerosolized pentamidine. JAMA. 1990; 263:2510-4. [PubMed 2184263]

292. Montaner JSG, Lawson LM, Gervais A et al. Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia: a randomized, placebo-controlled study. Ann Intern Med. 1991; 114:948-53. [IDIS 281383] [PubMed 2024862]

293. Smaldone GC, Perry RJ, Deutsch DG. Characteristics of nebulizers used in the treatment of AIDS-related Pneumocystis carinii pneumonia. J Aerosol Med. 1988; 1:113-26.

294. Smaldone RC, Vinciguerra C, Marchese J. Detection of inhaled pentamidine in health care workers. N Engl J Med. 1991; 325:891-2. [IDIS 285443] [PubMed 1875979]

295. Hirschel B, Lazzarin A, Chopard P et al. A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia. N Engl J Med. 1991; 324:1079-83. [IDIS 279604] [PubMed 2008181]

296. Smaldone GC, Fuhrer J, Steigbigel RT et al. Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection. Am Rev Respir Dis. 1991; 143:727-37. [IDIS 280712] [PubMed 2008984]

315. Quieffin J, Hunter J, Schecter MT et al. Aerosol pentamidine-induced bronchoconstriction: predictive factors and preventive therapy. Chest. 1991; 100:624-7. [IDIS 288845] [PubMed 1832372]

316. Leigh TR, Wiggins J, Gazzard B et al. A comparison of several agents with two delivery systems for the prevention of airway narrowing induced by nebulised pentamidine isethionate. Respir Med. 1991; 85:527-31. [PubMed 1663642]

318. Levine SJ, Masur H, Gill VJ et al. Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus. Ann Rev Respir Dis. 1991; 144:760-4.

321. Cheung TW, Matta R, Neibart E et al. Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. Clin Infect Dis. 1993; 16:22-5. [IDIS 307822] [PubMed 8448314]

322. Underwood TW, Frye CB. Drug-induced pancreatitis. Clin Pharm. 1993; 12:440-8. [IDIS 314327] [PubMed 8403815]

324. Schneider MME, Hoepelman AIM, Eeftinck Schattenkerk JKM et al. A controlled trial of aerosolized pentamidine or trimethoprim–sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. N Engl J Med. 1992; 327: 1836-41.

325. Hardy WD, Feinberg J, Finkelstein DM et al. A controlled trial of trimethoprim–sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patient with the acquired immunodeficiency syndrome: AIDS Clinical Trials Group protocol 021. N Engl J Med. 1992; 327:1842-8. [IDIS 306717] [PubMed 1448121]

330. Harb GE, Jacobson MA. Human immunodeficiency virus (HIV) infection: does it increase susceptibility to adverse drug reactions? Drug Safety. 1993; 9:1-8.

335. O'Neil MG, Selub SE, Hak LJ. Pancreatitis during pentamidine therapy in patients with AIDS. Clin Pharm. 1991; 10:56-9. [IDIS 276570] [PubMed 1999087]

337. Jones RS Jr, Collier-Brown C, Suh B. Localized cutaneous reaction to intravenous pentamidine. Clin Infect Dis. 1992; 15:561-2. [IDIS 301082] [PubMed 1387809]

338. McDiarmid MA, Fujikawa J, Schaefer J et al. Health effects and exposure assessment of aerosolized pentamidine handlers. Chest. 1993; 104:382-85. [IDIS 319800] [PubMed 8339622]

342. May T, Beuscart C, Reynes J et al. Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. J Acquir Immune Defic Syndr. 1994; 7:457-62. [IDIS 328947] [PubMed 8158539]

352. Zanetti LAF. Pentamidine-induced torsades de pointes. Ann Pharmacother. 1994; 28:282-3.

354. Dohn MN, Weinberg WG, Torres RA et al. Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Ann Intern Med. 1994; 121:174-80. [IDIS 332897] [PubMed 7880228]

355. Schwebke K, Fletcher CV, Acost EP et al. Pentamidine concentrations in a mother with AIDS and in her neonate. Clin Infect Dis. 1995; 20:1569-70. [IDIS 349029] [PubMed 7548518]

357. Furrer H, Egger M, Opravil M et al. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infected adults treated with combination antiretroviral therapy. N Engl J Med. 1999; 340:1301-6. [IDIS 425566] [PubMed 10219064]

367. Centers for Disease Control and Prevention. African trypanosomiasis – resources for health professionals. From CDC website. Accessed 2014 Jun 6. [IDIS www.cdc.gov/parasites/sleepingsickness/health_professionals/]

368. Brun R, Blum J, Chappuis F et al. Human African trypanosomiasis. Lancet. 2010; 375:148-59. [PubMed 19833383]

369. Kappagoda S, Singh U, Blackburn BG. Antiparasitic therapy. Mayo Clin Proc. 2011; 86:561-83. [PubMed 21628620]

370. Bronner U, Gustafsson LL, Doua F et al. Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness. Br J Clin Pharmacol. 1995; 39:289-95. [PubMed 7619671]

371. Centers for Disease Control and Prevention. Leishmaniasis – resources for health professionals. From CDC website. Accessed 2014 Jun 6. [IDIS www.cdc.gov/parasites/leishmaniasis/health_professionals/]

372. Murray HW. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg. 2012; 86:434-40. [PubMed 22403313]

373. Mitropoulos P, Konidas P, Durkin-Konidas M. New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment. J Am Acad Dermatol. 2010; 63:309-22. [PubMed 20303613]

374. Monge-Maillo B, López-Vélez R. Therapeutic options for old world cutaneous leishmaniasis and new world cutaneous and mucocutaneous leishmaniasis. Drugs. 2013; 73:1889-920. [PubMed 24170665]

375. Monge-Maillo B, López-Vélez R. Therapeutic options for visceral leishmaniasis. Drugs. 2013; 73:1863-88. [PubMed 24170666]

376. Olliaro PL, Guerin PJ, Gerstl S et al. Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980-2004. Lancet Infect Dis. 2005; 5:763-74. [PubMed 16310148]

377. Centers for Disease Control and Prevention. Health information for international travel, 2014. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

378. Ros JJ, Langen MC, Stallen PC et al. Pentamidine aerosols and environmental contamination: health-care workers at risk. Pharm World Sci. 1996; 18:148-52. [PubMed 8873231]

379. Ito S, Koren G. Estimation of fetal risk from aerosolized pentamidine in pregnant healthcare workers. Chest. 1994; 106:1460-2. [PubMed 7956402]

380. Decker JA, Seitz TA, Shults RA et al. Occupational exposures to aerosolized pharmaceuticals and control strategies. Scand J Work Environ Health. 1992; 18 Suppl 2:100-2. [PubMed 1514061]

381. Balmes JR, Estacio PL, Quinlan P et al. Respiratory effects of occupational exposure to aerosolized pentamidine. J Occup Environ Med. 1995; 37:145-50. [PubMed 7655955]

382. Centers for Disease Control and Prevention. Clinical management advice for confirmed or suspected cases of parasitic diseases. From CDC website. Accessed 2014 Jun 6.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:926-7.

Hide
(web3)