Pentamidine Isethionate and Renal dysfunction

• Generic Name: pentamidine
• Dosage Forms: n.a.
• Other Brand Names: Nebupent, Pentam 300, Pentam

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 who cannot tolerate drug of choice (co-trimoxazole).

Treatment of early or first-stage (hemolymphatic) trypanosomiasis caused by Trypanosoma brucei gambiense (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 (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.

Has been used for treatment of cutaneous and mucocutaneous leishmaniasis 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 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.

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.