Pentamidine (Systemic, Local) (Monograph)

Brand names: NebuPent, Pentam
Drug class:
- Antiprotozoal Agents

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antiprotozoal and antifungal; aromatic diamidine derivative.

Uses for Pentamidine (Systemic, Local)

Pneumocystis jirovecii Pneumonia

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

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

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. Some clinicians prefer primaquine and clindamycin regimen since it may be more effective and associated with lower toxicity compared with IV pentamidine. 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; treatment can be switched to appropriate oral regimen (e.g., atovaquone) after initial response is obtained with IV pentamidine.

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^{† [off-label]} who cannot tolerate drug of choice (co-trimoxazole).

African Trypanosomiasis

Treatment of early or first-stage (hemolymphatic) trypanosomiasis caused by Trypanosoma brucei gambiense^{† [off-label]} (West African trypanosomiasis, gambiense sleeping sickness). Drug of choice for first-stage T. b. gambiense infection; 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.

Has been used for treatment of early or first-stage (hemolymphatic) trypanosomiasis caused by T. b. rhodesiense^{† [off-label]} (East African trypanosomiasis, rhodesiense sleeping sickness). Suramin (not commercially available in US, but may be available from CDC) usually drug of choice for first-stage T. b. rhodesiense infection; pentamidine is an alternative, but may be less effective in these infections than in T. b. gambiense infections.

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. 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; melarsoprol (not commercially available in US, but may be available from CDC) usually recommended for treatment of T. b. rhodesiense infection with CNS involvement.

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

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. Contact CDC Drug Service at 404-639-3670 for information on how to obtain antiparasitic drugs not commercially available in US.

Leishmaniasis

Has been used for treatment of cutaneous and mucocutaneous leishmaniasis^{† [off-label]} caused by various Leishmania spp. 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; other options include amphotericin B, miltefosine, pentamidine, and ketoconazole. Although pentamidine has been recommended for treatment of New World cutaneous leishmaniasis^{† [off-label]} caused by L. guyanensis or L. panamensis, variable efficacy and potential adverse effects limit its usefulness for other types of cutaneous leishmaniasis.

Has been used for treatment of visceral leishmaniasis^† (also known as kala-azar). 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, but drug resistance and treatment failures are concerns in some areas (e.g., India, Nepal). Other options include amphotericin B, miltefosine, or paromomycin. Pentamidine not usually recommended because of variable or suboptimal efficacy and potential adverse effects.

Leishmaniasis is caused by >15 different Leishmania species that are transmitted to humans by bite of infected sand flies; also can be transmitted via blood (e.g., blood transfusions, needles shared by IV drug abusers) and perinatally from mother to infant. 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. Leishmaniasis reported in short-term travelers to endemic areas and in immigrants and expatriates from such areas; also reported in US military personnel and contract workers serving or working in endemic areas (e.g., Iraq, Afghanistan).

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). 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). No single treatment approach is appropriate for all possible clinical presentations. Consultation with clinicians experienced in management of leishmaniasis recommended.

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. Contact CDC Drug Service at 404-639-3670 for information on how to obtain antiparasitic drugs not commercially available in US.

Babesiosis

Has been used in some patients for treatment of babesiosis^† caused by Babesia microti; efficacy not established.

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

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

Related/similar drugs

clindamycin, sulfamethoxazole / trimethoprim, Bactrim, dapsone, leucovorin, amphotericin b, atovaquone

Pentamidine (Systemic, Local) Dosage and Administration

Administration

Administer by IM injection or slow IV infusion.

Administer by oral inhalation via nebulization.

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

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. (See Hypotension and Other Cardiovascular Effects under Cautions.)

IV Infusion

Position IV needle or catheter carefully; observe throughout period of administration. Avoid extravasation; if extravasation occurs, immediately stop infusion and restart at another site. (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. Do not reconstitute using sodium chloride solution; precipitation will occur.

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

Rate of Administration

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

IM Injection

Administer by deep IM injection.

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).

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. Do not reconstitute using sodium chloride solution; precipitation will occur.

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.

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

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

Reconstitution

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

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. 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.

Dosage

Available as pentamidine isethionate; dosage expressed as pentamidine isethionate.

Pediatric Patients

Pneumocystis jirovecii Pneumonia (PCP)

Treatment of PCP

IM or IV

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

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

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

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).

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

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

Criteria for initiating or discontinuing primary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults. (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).

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

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

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.

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. Assess CD4⁺ T-cell count and CD4⁺ percentage every 3 month; reinitiate if indicated based on age-specific thresholds.

Criteria for initiating or discontinuing secondary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults. (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. Give IM or, alternatively, by IV infusion over 2 hours.

Treatment of First-stage Trypanosoma brucei rhodesiense Infection†

IM or IV

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

Leishmaniasis†

Treatment of Cutaneous Leishmaniasis†

IM or IV

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

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

Treatment of Visceral Leishmaniasis†

IM or IV

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

Adults

Pneumocystis jirovecii Pneumonia (PCP)

Treatment of Moderate to Severe PCP

IM or IV

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

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

Prevention of Initial Episode (Primary Prophylaxis) of PCP

Oral Inhalation via Nebulization

300 mg once every 4 weeks (once monthly).

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

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.

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

Prevention of Recurrence (Secondary Prophylaxis) of PCP

Oral Inhalation via Nebulization

300 mg once every 4 weeks (once monthly).

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

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. Reinitiate if CD4⁺ T-cell count decreases to <200/mm³ or PCP recurs when CD4⁺ T-cell count >200/mm³.

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.

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. Give IM or, alternatively, by IV infusion over 2 hours.

Treatment of First-stage Trypanosoma brucei rhodesiense Infection†

IM or IV

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

Leishmaniasis†

Treatment of Cutaneous Leishmaniasis†

IM or IV

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

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

Treatment of Visceral Leishmaniasis†

IM or IV

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

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.

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.

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 Cl_cr 10–50 mL/minute and 4 mg/kg once every 48 hours in those with Cl_cr <10 mL/minute.

Cautions for Pentamidine (Systemic, Local)

Contraindications

• IV or IM: Known hypersensitivity to pentamidine.

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

Warnings/Precautions

Warnings

Hypotension and Other Cardiovascular Effects

IV or IM: Hypotension, which may develop suddenly and may be moderate to severe, can occur. Fatalities due to severe hypotension or cardiac arrhythmias reported. Hypotensive reactions most likely with rapid IV injection or infusion.

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

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

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

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

Local Effects

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

IM: Sterile abscess and/or necrosis, pain, erythema, tenderness, and induration at injection site.

Hypoglycemia and Diabetogenic Effects

Hypoglycemia, which may be severe and has been fatal in some cases, reported with IM or IV pentamidine. Has been associated with pancreatic islet cell necrosis and inappropriately high plasma insulin concentrations.

Hyperglycemia and insulin-dependent diabetes mellitus (which appears to be permanent in some cases) has occurred with or without preceding hypoglycemia and ketoacidosis in patients receiving parenteral pentamidine.

Hypoglycemia, hyperglycemia, and diabetes 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.

Use with caution in patients with hypoglycemia or hyperglycemia.

Pancreatitis

Acute pancreatitis (sometimes fatal) reported with IM or IV pentamidine. Acute pancreatitis also reported rarely in patients receiving pentamidine by oral inhalation via nebulization.

Use with caution in patients with pancreatitis. Discontinue if acute pancreatitis occurs.

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.

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

Patients receiving the drug for prevention of PCP may still develop acute PCP. Extrapulmonary and/or disseminated P. jirovecii infection also reported occasionally during PCP prophylaxis, usually in patients with a history of PCP.

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. If PCP develops, discontinue prophylaxis and initiate treatment with co-trimoxazole, parenteral pentamidine, or another effective regimen. PCP prophylaxis can be reinstituted when treatment is complete.

Respiratory Effects

Cough and bronchospasm reported frequently when pentamidine administered by oral inhalation via nebulization, especially in those with a history of smoking or asthma. Bronchospasm also reported after parenteral administration.

Cough or bronchospasm in patients receiving pentamidine by oral inhalation can be controlled in most patients by interrupting pentamidine treatment and administering a bronchodilator. Coughing also may be controlled by slowing the delivery or intensity of the pentamidine aerosol stream.

Pretreatment with an orally inhaled bronchodilator may minimize occurrence of coughing and bronchospasm.

Sensitivity Reactions

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

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

Pruritus, local or generalized urticaria, rash (e.g., maculopapular, pruritic) also reported with IM or IV administration.

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

Major Toxicities

Renal Effects

IM or IV: Nephrotoxicity (increase in S_cr and/or BUN, azotemia, renal insufficiency, renal failure) reported.

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

Monitor renal function (BUN, S_cr) before, during (daily or every other day), and after therapy. Consider monitoring serum potassium concentrations, particularly in AIDS patients.

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

Hepatic Effects

IM or IV: Elevated liver function test results reported.

Hepatitis, hepatomegaly, and hepatic dysfunction 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. (See Hepatic Impairment under Cautions.)

Hematologic Effects

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

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

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

General Precautions

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

Laboratory Monitoring

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

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

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

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

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. Measurable levels of pentamidine can be present in room air when pentamidine is administered by oral inhalation via nebulization.

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

Cough and bronchospasm frequently occur in patients receiving pentamidine by oral inhalation via nebulization; 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).

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, 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.

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.

Because potential risks, particularly long-term and cumulative effects, associated with environmental exposure to aerosolized pentamidine not established, health-care facilities should have procedures to minimize environmental exposure to aerosolized pentamidine. Consult specialized sources for recommended procedures.

Specific Populations

Pregnancy

Category C.

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.

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. (See Environmental Exposure of Health-care Personnel and Visitors under Cautions.)

Lactation

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

Pediatric Use

IM or IV: Safety and efficacy established for treatment of PCP in children >4 months of age; no unusual risks identified. Also has been used effectively and apparently without unusual risks in children for treatment of first-stage (hemolymphatic) African trypanosomiasis^† and for treatment of leishmaniasis^†.

Oral inhalation via nebulization: Manufacturer states safety and efficacy not established in children ≤16 years of age. 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.

Hepatic Impairment

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

Oral inhalation via nebulization: Pharmacokinetic data not available.

Renal Impairment

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

Oral inhalation via nebulization: Pharmacokinetic data not available.

Common Adverse Effects

IM or IV: Nephrotoxicity, hypotension, hepatic effects, GI effects (anorexia, nausea, vomiting), hematologic effects (leukopenia), hypoglycemia, injection site reactions.

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

Drug Interactions

Nephrotoxic Drugs

Closely monitor or avoid concurrent or sequential use with other nephrotoxic drugs since nephrotoxic effects may be additive.

Specific Drugs

Pentamidine (Systemic, Local) Pharmacokinetics

Absorption

Bioavailability

Well absorbed following IM administration.

Bronchoalveolar lavage fluid concentrations attained following oral inhalation are substantially higher (at least 5–10 times) than those attained following IV administration.

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

Plasma Concentrations

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

Special Populations

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

Distribution

Extent

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

Penetrates the CNS poorly.

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.

Crosses the placenta; not known whether distributed into milk.

Plasma Protein Binding

69%.

Elimination

Elimination Route

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

Not appreciably removed by hemodialysis or peritoneal dialysis.

Half-life

IV: 6.4 hours.

IM: 9.4 hours.

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

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.

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

Stability

Storage

Parenteral

Powder for IM or IV Use

20–25°C; protect from light.

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

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.

Oral Inhalation via Nebulization

Powder for Inhalation Solution

20–25°C; protect from light.

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

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Oral Inhalation

Do not mix with other drugs.

Actions and Spectrum

• The exact mechanism(s) of antiprotozoal action not fully elucidated; interferes with protozoal nuclear metabolism by inhibiting DNA, RNA, phospholipid, and protein synthesis.

• Spectrum of activity includes many protozoa and some fungi.

• Active in vivo and in vitro against P. jirovecii (formerly P. carinii). In vitro studies indicate the drug appears to be directly lethal to P. jirovecii at concentrations attainable in vivo.

• Active in vitro and/or in vivo against causative agents of African trypanosomiasis, including most strains of T. b. gambiense and some strains of T. b. rhodesiense; not active against T. cruzi (causative agent of American trypanosomiasis [Chagas disease]).

• Active in vitro and/or in vivo against L. donovani (including antimony-resistant strains) and L. aethiopica.

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

Advice to Patients

• Importance of completing full course of therapy.

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

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

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