Pentamidine Mesilate

(BANM, rINNM)
Synonyms: Mesilato de pentamidina; Pentamidine Dimethylsulphonate; Pentamidine, Mésilate de; Pentamidine Mesylate; Pentamidine Methanesulphonate; Pentamidini Mesilas; RP-2512. Pentamidine dimethanesulphonate.
Cyrillic synonym: Пентамидина Мезилат.

💊 Chemical information

Chemical formula: C19H24N4O2,2CH3SO3H = 532.6.
CAS — 6823-79-6.

Pharmacopoeias.

In Int.

💊 Adverse Effects

Pentamidine is a toxic drug and adverse effects are frequent and sometimes severe when given parenterally; fatalities have been reported. Renal impairment is common, usually manifesting as mild and reversible raised blood urea nitrogen and serum creatinine concentrations, but acute renal failure can occur. Raised liver enzyme values and haematological disturbances such as leucopenia, anaemia, and occasionally thrombocytopenia, may develop. Hypoglycaemia, sometimes followed by hyperglycaemia and type 1 diabetes mellitus, is well documented; there have been occasional reports of acute pancreatitis. The rapid intravenous injection of pentamidine has resulted in sudden hypotension and immediate reactions such as dizziness, headache, vomiting, breathlessness, tachycardia, and fainting. Hypotension may also occur when pentamidine is given intramuscularly or by slow intravenous infusion. Intramuscular pentamidine often causes pain, swelling, sterile abscess formation, and tissue necrosis at the site of injection. Similar damage can follow extravasation during intravenous dosage. Other adverse effects reported include hypocalcaemia, hyperkalaemia, skin rashes, the Stevens-Johnson syndrome, fever, flushing, gastrointestinal effects such as nausea, vomiting, and taste disturbances, confusion, hallucinations, and cardiac arrhythmias. Pentamidine is not as toxic when given by inhalation for the prophylaxis of pneumocystis pneumonia. The commonest adverse effects with this route are cough and bronchoconstriction and may be controlled by a bronchodilator. Inhalation may leave a bitter taste. Pneumothorax has been reported, but may be associated with the disease. There have been rare reports of adverse effects such as those seen when pentamidine is given by injection.

Incidence of adverse effects.

Adverse effects were seen in 46.8% of 404 patients given pentamidine parenterally for the treatment of pneumocystis pneumonia, according to an analysis from the CDC in the USA.1 The reactions included impaired renal function (23.5% of patients), abnormal liver function (9.6%), hypoglycaemia (6.2%), haematological disturbances (4.2%), skin rashes (1.5%), and hypocalcaemia (1.2%). Local reactions at injection sites such as pain and abscess occurred in 18.3% and immediate adverse effects such as hypotension in 9.6%. Retrospective studies2-4 suggest that adverse reactions occur more commonly in patients with AIDS. An evaluation of pentamidine in the treatment of 82 patients with visceral leishmaniasis further illustrates its toxicity.5 Cardiotoxicity (tachycardia, hypotension, and ECG changes of non-specific myocarditis), occurred in about 23% of patients. No hypoglycaemic reaction was noted, but 4 patients developed diabetes mellitus and 3 of them were found to be insulin-dependent. Other adverse reactions included gastrointestinal effects (anorexia, nausea, vomiting, abdominal pain, or diarrhoea) in about 78%, CNS effects (headache associated with flushing, delirium, or sensory disturbances resembling pins and needles) in about 24%, mild reversible albuminuria in about 7%, and allergic manifestations (generalised urticaria, itching, and conjunctival congestion) in about 5%. One patient had severe anaphylaxis.
1. Walzer PD, et al. Pneumocystis carinii pneumonia in the United States: epidemiologic, diagnostic and clinical features. Ann Intern Med 1974; 80: 83–93
2. Lachaal M, Venuto RC. Nephrotoxicity and hyperkalemia in patients with acquired immunodeficiency syndrome treated with pentamidine. Am J Med 1989; 87: 260–3
3. Briceland LL, Bailie GR. Pentamidine-associated nephrotoxicity and hyperkalemia in patients with AIDS. DICP Ann Pharmacother 1991; 25: 1171–4
4. O’Brien JG, et al. A 5-year retrospective review of adverse drug reactions and their risk factors in human immunodeficiency virus-infected patients who were receiving intravenous pentamidine therapy for Pneumocystis carinii pneumonia. Clin Infect Dis 1997; 24: 854–9
5. 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.

Effects on the blood.

Haemolytic anaemia has been reported in a 55-year-old man with AIDS being treated with intravenous pentamidine for pneumocystis pneumonia. Symptoms developed after a cumulative dose of 3740 mg of pentamidine had been given and resolved several days after stopping the pentamidine.1
1. Taguchi H, et al. Pentamidine-induced hemolytic anemia in an AIDS patient. Ann Pharmacother 1999; 33: 503.

Effects on carbohydrate metabolism.

As reported under Incidence of Adverse Effects, above, pentamidine can have a range of effects on carbohydrate metabolism. Four patients receiving pentamidine for pneumocystis pneumonia developed severe fasting hypoglycaemia followed later by hyperglycaemia and type 1 diabetes mellitus.1 It has been suggested that pentamidine has a toxic effect on the β-cells of the pancreatic islets and can induce an early cytolytic release of insulin and hypoglycaemia, followed by β-cell destruction, insulin deficiency, and diabetes mellitus.1,2 AIDS patients appear to be highly susceptible and have a higher incidence of hypoglycaemia due to pentamidine.3 The action on the pancreas has led to fatal acute pancreatitis;4-6 fatal hypoglycaemia has also been reported.7 These reports1-5,7 involved pentamidine given by injection; pancreatitis8,9 and diabetes mellitus10,11 have also been reported in patients given pentamidine by aerosol inhalation.
1. Bouchard P, et al. Diabetes mellitus following pentamidine-induced hypoglycemia in humans. Diabetes 1982; 31: 40–5
2. Osei K, 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
3. Stahl-Bayliss CM, et al. Pentamidine-induced hypoglycemia in patients with the acquired immune deficiency syndrome. Clin Pharmacol Ther 1986; 39: 271–5
4. Salmeron S, et al. Pentamidine and pancreatitis. Ann Intern Med 1986; 105: 140–1
5. Zuger A, et al. Pentamidine-associated fatal acute pancreatitis. JAMA 1986; 256: 2383–5
6. Sauleda J, et al. Probable pentamidine-induced acute pancreatitis. Ann Pharmacother 1994; 28: 52–3
7. Sattler FR, Waskin H. Pentamidine and fatal hypoglycemia. Ann Intern Med 1987; 107: 789–90
8. Herer B, et al. Pancreatitis associated with pentamidine by aerosol. BMJ 1989; 298: 605
9. Hart CC. Aerosolized pentamidine and pancreatitis. Ann Intern Med 1989; 111: 691
10. Fisch A. Diabetes mellitus in a patient with AIDS after treatment with pentamidine aerosol. BMJ 1990; 301: 875
11. Chen JP, et al. Diabetes after aerosolized pentamidine. Ann Intern Med 1991; 114: 913–14.

Effects on the cardiovascular system.

Hypotension is a problem with intravenous pentamidine, but can be reduced by infusing the dose over 60 minutes, when the incidence of hypotension appears to be similar to that with the intramuscular route.1,2 Intravenous pentamidine has also been associated with torsade de pointes.3-5
1. Navin TR, Fontaine RE. Intravenous versus intramuscular administration of pentamidine. N Engl J Med 1984; 311: 1701.
2. Helmick CG, Green JK. Pentamidine-associated hypotension and route of administration. Ann Intern Med 1985; 103: 480
3. Harel Y, et al. Pentamidine-induced torsade de pointes. Pediatr Infect Dis J 1993; 12: 692–4
4. Miller HC. Cardiac arrest after intravenous pentamidine in an infant. Pediatr Infect Dis J 1993; 12: 694–6
5. Zanetti LAF, Oliphant CM. Pentamidine-induced torsade de pointes. Ann Pharmacother 1994; 28: 282–3.

Effects on the kidneys.

In an analysis1 of the adverse effects of parenteral pentamidine (see also under Incidence of Adverse Effects above), nephrotoxicity was often the most serious adverse reaction, although it was impossible to attribute it solely to pentamidine. Severe renal impairment occurred in 15 of 404 patients and contributed materially to 12 of 14 ensuing deaths. However, elevation of blood urea nitrogen was usually relatively mild and reversible in those patients who had normal pretreatment renal function and had received no other nephrotoxic agents. In two studies in patients with AIDS,2,3 severe nephrotoxicity (increase in serum creatinine concentration of 0.5 mg per 100 mL) was reported in about 40% of patients. Analysis of risk factors suggested that the development of adverse reactions to parenteral pentamidine is correlated with the total dose received and the duration of treatment,2,3 but not with the initial degree of renal function.2 It has been observed that renal toxicity is more common when pentamidine is given intramuscularly, rather than intravenously, to AIDS patients with diarrhoea, suggesting that fluid status might have an important role.4 There have been instances of renal failure occurring when pentamidine is inhaled as an aerosol for its local effect.5,6
1. Walzer PD, et al. Pneumocystis carinii pneumonia in the United States: epidemiologic, diagnostic and clinical features. Ann Intern Med 1974; 80: 83–93
2. Briceland LL, Bailie GR. Pentamidine-associated nephrotoxicity and hyperkalemia in patients with AIDS. DICP Ann Pharmacother 1991; 25: 1171–4
3. O’Brien JG, et al. A 5-year retrospective review of adverse drug reactions and their risk factors in human immunodeficiency virus-infected patients who were receiving intravenous pentamidine therapy for Pneumocystis carinii pneumonia. Clin Infect Dis 1997; 24: 854–9
4. Stehr-Green JK, Helmick CG. Pentamidine and renal toxicity. N Engl J Med 1985; 313: 694–5
5. Miller RF, et al. Acute renal failure after nebulised pentamidine. Lancet 1989; i: 1271–2
6. Chapelon C, et al. Renal insufficiency with nebulised pentamidine. Lancet 1989; ii: 1045–6.

Effects on the nervous system.

Paraesthesias have been reported with pentamidine therapy. Perioral numbness occurred in a patient soon after starting the third intravenous infusion of pentamidine for treatment of pneumocystis pneumonia and disappeared after the end of the infusion; numbness recurred with all subsequent pentamidine infusions.1
1. Milligan KS, Phillips DL. Perioral numbness associated with intravenous pentamidine administration. Ann Pharmacother 2007; 41: 153–6.

Effects on the respiratory system.

Although inhaled pentamidine has produced reactions that are normally associated with the parenteral route, the main problem after inhalation is bronchoconstriction;1 it can be prevented by prior use of a bronchodilator. Acute eosinophilic pneumonia associated with nebulised pentamidine has been reported in a patient.2 Concern has also been expressed at the risks to those who are with the patient at the time of inhalation and are exposed to nebulised pentamidine.3-5
1. Smith DE, et al. Reversible bronchoconstriction with nebulised pentamidine. Lancet 1988; ii: 905
2. Dupon M, et al. Acute eosinophilic pneumonia induced by inhaled pentamidine isethionate. BMJ 1993; 306: 109
3. McDiarmid MA, Jacobson-Kram D. Aerosolised pentamidine and public health. Lancet 1989; ii: 863–4
4. Thomas SHL, et al. Aerosolised pentamidine. Lancet 1989; ii: 1284
5. Smaldone GC, et al. Detection of inhaled pentamidine in health care workers. N Engl J Med 1991; 325: 891–2.

💊 Precautions

Pentamidine should be used under close supervision and great care is necessary if it is used in patients suffering from any condition likely to be exacerbated by its adverse effects. The CSF should be checked for signs of CNS involvement before giving pentamidine for trypanosomiasis, since it is unlikely to be effective in such cases. Patients should remain supine while it is given and their blood pressure should be monitored. Kidney and liver function, blood-glucose concentrations, blood and platelet counts, and other parameters indicative of developing toxicity, such as serumcalcium concentrations and the ECG, should also be assessed regularly during courses of treatment with pentamidine. Patients with a history of asthma or smoking may be at increased risk of cough and bronchospasm during inhalation of nebulised pentamidine. Symptoms may be controlled by giving a bronchodilator before pentamidine. Pentamidine solution should not be mixed with other drugs nor should a bronchodilator be given in the same nebuliser. Extrapulmonary Pneumocystis jirovecii infections may occur in patients given nebulised pentamidine and should be considered in patients with unexplained signs and symptoms. Precautions should be taken to minimise atmospheric pollution with pentamidine during nebulisation and to minimise exposure of medical personnel to pentamidine.

💊 Interactions

Use of pentamidine with other nephrotoxic drugs such as amphotericin B or foscarnet should preferably be avoided. Extreme caution is also necessary if pentamidine is given with other drugs, such as foscarnet, that can cause hypocalcaemia. There is an increased risk of ventricular arrhythmias if pentamidine is given with drugs which prolong the QT interval such as amiodarone, levacetylmethadol, or terfenadine. There may be an increased risk of pancreatitis when intravenous pentamidine is used with didanosine or zalcitabine and such combinations should be avoided.

💊 Pharmacokinetics

After intravenous doses of the isetionate, pentamidine is rapidly distributed to body tissues and this is followed by a prolonged elimination phase. Elimination half-lives of 6 hours after intravenous infusion and 9 hours after intramuscular injection have been cited, but probably represent an intermediate value, and terminal elimination half-lives of between several days and weeks have been reported. During repeated dosing accumulation is believed to occur, particularly in the liver and kidneys, and only small concentrations of pentamidine are found in the urine. Distribution to the lung is relatively poor after injection. Systemic absorption after inhalation is reported to result in peak plasma concentrations of 5 to 10% of those after parenteral use, and there have been a few reports of systemic adverse effects. Particle or droplet size appears to be important in achieving adequate pulmonary distribution.
1. O’Doherty MJ, et al. Differences in relative efficiency of nebulisers for pentamidine administration. Lancet 1988; ii: 1283–6
2. Simonds AK, et al. Aerosolised pentamidine. Lancet 1989; i: 221–2
3. Baskin MI, et al. Regional deposition of aerosolized pentamidine: effects of body position and breathing pattern. Ann Intern Med 1990; 113: 677–83
4. Bronner U, et al. Pentamidine concentrations in plasma, whole blood and cerebrospinal fluid during treatment of Trypanosoma gambiense in Côte d’Ivoire. Trans R Soc Trop Med Hyg 1991; 85: 608–11
5. Lidman C, et al. Plasma pentamidine concentrations vary between individuals with Pneumocystis carinii pneumonia and the drug is actively secreted by the kidney. J Antimicrob Chemother 1994; 33: 803–10
6. Bronner U, 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
7. Conte JE, Golden JA. Intrapulmonary and systemic pharmacokinetics of aerosolized pentamidine used for prophylaxis of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus. J Clin Pharmacol 1995; 35: 1166–73.

Renal impairment.

In a study1 of patients with normal renal function or on haemodialysis, renal clearance of pentamidine during the 24 hours after intravenous use was 2.1% of the plasma clearance in those with normal renal function, suggesting that pentamidine elimination would be largely unaffected by renal impairment. In those with end-stage renal disease on haemodialysis the terminal elimination half-life after a single dose was prolonged to about 75 hours, compared with 30 hours in the patients with normal renal function, but the volumes of distribution and area under the concentration-time curve were not significantly different. In patients with normal or mildly impaired renal function who had received between 12 and 21 doses, the terminal elimination half-life after the final dose was about 12 days and pentamidine was still detectable in the plasma after 6 weeks. There was evidence of accumulation of pentamidine during repeated daily dosing.
1. Conte JE. Pharmacokinetics of intravenous pentamidine in patients with normal renal function or receiving hemodialysis. J Infect Dis 1991; 163: 169–75.

💊 Uses and Administration

Pentamidine, an aromatic diamidine derivative, is an antiprotozoal used in the treatment of the early stages of African trypanosomiasis, especially Trypanosoma brucei gambiense infections, and in some forms of leishmaniasis. It is also used in the treatment and prophylaxis of pneumocystis pneumonia. It may act by several mechanisms, including interference with protozoal DNA and folate transformation and by inhibition of RNA and protein synthesis. Pentamidine has been given as the isetionate or mesilate salt, but the isetionate is the only form now available in most countries. There is considerable confusion in the literature regarding the dosage of pentamidine since it is often not clear whether doses are being expressed in terms of pentamidine base, the isetionate salt, or the mesilate salt. In general it would appear that when the isetionate is used doses are expressed in terms of pentamidine isetionate, whereas when the mesilate is used doses are expressed in terms of pentamidine base. Pentamidine isetionate 4 mg/kg is equivalent to about 2.3 mg/kg of pentamidine base; pentamidine mesilate 3.6 mg/kg is equivalent to about 2.3 mg/kg of pentamidine base. Pentamidine isetionate is given by deep intramuscular injection or by slow intravenous infusion over at least 60 minutes; direct intravenous injection must be avoided. Patients should be lying down. The mesilate has usually been given intramuscularly. In the treatment of early African trypanosomiasis due to T. b. gambiense, pentamidine isetionate 4 mg/kg may be given daily or on alternate days by intramuscular injection or intravenous infusion to a total of 7 to 10 doses. Pentamidine is not effective in trypanosomiasis with CNS involvement, but 2 doses of pentamidine may be given in late-stage T. b. gambiense infection before starting treatment with melarsoprol or eflornithine. In the treatment of visceral leishmaniasis, and of mucocutaneous leishmaniasis due to Leishmania braziliensis or L. aethiopica that have not responded to antimonials, pentamidine isetionate 4 mg/kg may be given, preferably intramuscularly three times weekly, for 5 to 25 weeks or longer. An alternative regimen in visceral leishmaniasis is to give 3 to 4 mg/kg on alternate days to a maximum of 10 injections; the course may need to be repeated. In cutaneous leishmaniasis due to L. aethiopica or L. guyanensis, pentamidine isetionate 3 to 4 mg/kg may be given, preferably intramuscularly once or twice weekly, until the condition resolves. A weekly dose of 3 to 4 mg/kg is also used for diffuse cutaneous leishmaniasis due to L. aethiopica and should be continued for at least 4 months after parasites are no longer detectable on skin smears. In the treatment of pneumocystis pneumonia, pentamidine isetionate 4 mg/kg is given once daily for 14 days or longer, by intramuscular injection or preferably slow intravenous infusion. Pentamidine isetionate is given by inhalation through a nebuliser to prevent pneumocystis pneumonia in HIV-positive patients in a dose of 300 mg once every 4 weeks; in those who cannot tolerate this dose 150 mg every 2 weeks may be used. It has also occasionally been used by this route for treating mild to moderate P. jirovecii infection in a dose of 600 mg daily for 3 weeks. Nebuliser design can affect the droplet size delivered and hence the amount of pentamidine reaching sites of action within the lungs. The optimal particle size is 1 to 2 μm. Precautions should be taken to minimise atmospheric pollution with pentamidine during nebulisation and to minimise exposure of medical personnel to the drug.

Administration in renal impairment.

Since renal clearance accounts for only a small proportion of pentamidine elimination, dosage adjustment is not generally considered necessary for mild to moderate degrees of renal impairment. UK licensed product information recommends dosage reductions in patients with pneumocystis pneumonia who have a creatinine clearance of less than 10 mL/minute. In patients with life-threatening disease the recommended dose of 4 mg/kg daily should be given for 7 to 10 days and then on alternate days for the remainder of the 14-dose course. In less severe disease the suggested dose is 4 mg/kg on alternate days for 14 doses.

Amoebic infections.

ACANTHAMOEBA INFECTIONS. Pentamidine was used to treat disseminated Acanthamoeba infection without evidence of CNS involvement in 2 immunocompromised patients.1,2 It is unlikely that pentamidine would be effective in infections involving the CNS.
1. Slater CA, et al. Brief report: successful treatment of disseminated Acanthamoeba infection in an immunocompromised patient. N Engl J Med 1994; 331: 85–7
2. Murakawa GJ, et al. Disseminated Acanthamoeba in patients with AIDS: a report of five cases and a review of the literature. Arch Dermatol 1995; 131: 1291–6.

Babesiosis.

Pentamidine has been tried for babesiosis, but while some patients showed clinical improvements,1-3 the efficacy and safety of pentamidine in this infection has been questioned.4
1. Francioli PB, et al. Response of babesiosis to pentamidine therapy. Ann Intern Med 1981; 94: 326–30
2. Raoult D, et al. Babesiosis, pentamidine, and cotrimoxazole. Ann Intern Med 1987; 107: 944
3. Clarke CS, et al. Babesiosis: under-reporting or case-clustering? Postgrad Med J 1989; 65: 591–3
4. Teutsch SM, Juranek DD. Babesiosis. Ann Intern Med 1981; 95: 241.

Leishmaniasis.

Pentamidine has been used in the treatment of visceral leishmaniasis both alone and with antimonials in patients who have failed to respond to antimonials alone.1,2 It has also been tried for long-term secondary prophylaxis in patients with HIV infection.3 Cutaneous leishmaniasis due to L. guyanensis is usually treated with pentamidine to reduce the risk of dissemination;1 beneficial results in patients infected with L. infantum, L. major, or L. tropica have also been reported.4 Lesions due to L. aethiopica may also respond to pentamidine, but can be left to heal spontaneously since the risk of diffuse cutaneous involvement is small.1 Diffuse cutaneous or mucocutaneous disease which is unresponsive to antimonials may respond to pentamidine.1 For mention of the use of pentamidine with paromomycin to treat visceral leishmaniasis in an HIV-infected patient.
1. WHO. WHO model formulary. Geneva: WHO, 2004
2. Baily GG, Nandy A. Visceral leishmaniasis: more prevalent and more problematic. J Infect 1994; 29: 241–7
3. Pérez-Molina JA, et al. Pentamidine isethionate as secondary prophylaxis against visceral leishmaniasis in HIV-positive patients. AIDS 1996; 10: 237–8
4. Hellier I, et al. Treatment of Old World cutaneous leishmaniasis by pentamidine isethionate: an open study of 11 patients. Dermatology 2000; 200: 120–3.

Pneumocystis pneumonia.

In the treatment of pneumocystis pneumonia intravenous pentamidine is generally reserved for patients with moderate to severe disease who do not respond to, or cannot tolerate, co-trimoxazole. Co-trimoxazole with pentamidine is no more effective than pentamidine alone in these patients and is potentially more toxic than either drug.1 Inhaled pentamidine has occasionally been suggested for mild to moderate infection, but is now generally only used for prophylaxis. However, patients given inhaled pentamidine may be prone to extrapulmonary Pneumocystis infections.2,3 In both primary and secondary prophylaxis of pneumocystis pneumonia in immunocompromised patients, co-trimoxazole is preferred to inhaled pentamidine. Comparative studies have shown that, in the short term, inhaled pentamidine has been less effective than co-trimoxazole4,5 and no more effective than another common prophylactic drug, dapsone.6,7 In addition, both co-trimoxazole and dapsone (given with pyrimethamine) also provide protection against toxoplasmosis and extrapulmonary pneumocystis infections. However, inhaled pentamidine is better tolerated than either of these, and studies have suggested that in the long term the efficacy of the three drugs is comparable,8,9 at least in patients with CD4+ T lymphocyte counts of more than 100 cells/microlitre. Increasing the dose of pentamidine from 300 mg every four weeks to 300 mg every two weeks10,11 or 600 mg every week12 may improve efficacy further. Intermittent parenteral dosage of pentamidine has been used when the more usual drugs cannot be given.13
1. Glatt AE, Chirgwin K. Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients. Arch Intern Med 1990; 150: 271–9
2. Witt K, et al. Dissemination of Pneumocystis carinii in patients with AIDS. Scand J Infect Dis 1991; 23: 691–5
3. Sha BE, et al. Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. J Acquir Immune Defic Syndr Hum Retrovirol 1992; 5: 1051–8
4. Schneider MME, 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
5. Hardy WD, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med 1992; 327: 1842–8
6. Girard P-M, et al. Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. N Engl J Med 1993; 328: 1514–20
7. Torres RA, et al. Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. Am J Med 1993; 95: 573–83
8. Bozzette SA, et al. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995; 332: 693–9
9. Rizzardi GP, et al. Risks and benefits of aerosolized pentamidine and cotrimoxazole in primary prophylaxis of Pneumocystis carinii pneumonia in HIV-1-infected patients: a two-year Italian multicentric randomized controlled trial. J Infect 1996; 32: 123–31
10. Kronawitter U, et al. Low incidence of Pneumocystis carinii pneumonia in HIV patients receiving 300 mg pentamidine aerosol every 2 weeks. Clin Investig 1992; 70: 1089–91
11. Rizzardi GP, et al. Better efficacy of twice-monthly than monthly aerosolised pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS: an Italian multicentric randomised controlled trial. J Infect 1995; 31: 99–105
12. Ong ELC, et al. Efficacy and effects on pulmonary function tests of weekly 600 mg aerosol pentamidine as prophylaxis against Pneumocystis carinii pneumonia. Infection 1992; 20: 136–9
13. CDC. Guidelines for preventing opportunistic infections among HIV-infected persons—2002: recommendations of the US Public Health Service and the Infectious Diseases Society of America. MMWR 2002; 51 (RR-8): 1–52. Also available at: http:// www.cdc.gov/mmwr/PDF/rr/rr5108.pdf (accessed 27/05/05)

African trypanosomiasis.

Pentamidine is used for the haematolymphatic phase of African trypanosomiasis caused by Trypanosoma brucei gambiense, and as an adjunct to other treatment for the meningoencephalitic stage of the infection.1 It is reported to be less effective against T. b. rhodesiense and in some areas resistance of T. b. gambiense to pentamidine is increasing. Pentamidine has been used with suramin for T. b. gambiense infections but this has not been shown to be clinically superior to pentamidine alone.2
1. WHO. Control and surveillance of African trypanosomiasis: report of a WHO expert committee. WHO Tech Rep Ser 881 1998
2. Pépin J, Khonde N. Relapses following treatment of early-stage Trypanosoma brucei gambiense sleeping sickness with a combination of pentamidine and suramin. Trans R Soc Trop Med Hyg 1996; 90: 183–6.

💊 Preparations

BP 2008: Pentamidine Injection.

Proprietary Preparations

Austria: Pentacarinat; Belg.: Pentacarinat; Braz.: Pentacarinat; Sideron†; Canad.: Pentacarinat†; Denm.: Pentacarinat; Fin.: Pentacarinat†; Fr.: Pentacarinat; Ger.: Pentacarinat; Gr.: Pentacarinate; Pentam; Irl.: Pentacarinat; Israel: Pentacarinat†; Ital.: Pentacarinat; Neth.: Pentacarinat; NZ: Pentacarinat; Port.: Pentacarinat†; Pentamina; Spain: Pentacarinat; Swed.: Pentacarinat; Switz.: Pentacarinat; Thai.: Pentacarinat; UK: Pentacarinat; USA: NebuPent; Pentacarinat; Pentam.
Published December 16, 2018.