Pentamidine Disease Interactions

Parenteral use of pentamidine may be associated with serious and potentially fatal cardiovascular effects. Sudden and severe hypotension, cardiorespiratory arrest, ventricular tachycardia, torsade de pointes, ECG abnormalities, and facial flushing have been reported. Therapy with pentamidine should be administered cautiously in all patients but in particular, those with preexisting hypotension, severe cardiovascular disease, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Patients should be in a supine position and blood pressure monitored closely during and after administration of the drug until blood pressure is stable. Equipment for emergency resuscitation should be readily available if the parenteral route is used. ECGs should also be performed before, during, and after parenteral therapy.

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Patients who are dehydrated may be particularly susceptible to the nephrotoxic and hypotensive effects associated with the parenteral use of pentamidine. Dehydration should preferably be corrected prior to initiation of therapy. In patients who may be at risk for dehydration, such as those with severe and/or prolonged diarrhea or vomiting, fluid status and blood pressure should be monitored closely. If signs of renal irritation develop during therapy, hydration should be increased as indicated, accompanied by a reduction in dosage if necessary. Therapy should be withdrawn if urinary output decreases progressively or azotemia increases.

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Pentamidine may have direct toxic effects on beta cells of the pancreas. Hypoglycemia, which may be severe and/or prolonged, as well as hyperglycemia and insulin-dependent diabetes mellitus, the latter of which may be irreversible, have been reported. The onset of pentamidine-induced hypoglycemia generally varied from 5 to 7 days after start of therapy to several days after therapy stops. In some cases, hyperglycemia and progression to diabetes followed, although these effects have occurred independently also. Pancreatic toxicity has been reported with both parenteral use and, less frequently, oral inhalation of pentamidine. The risk appears to be related to total cumulative dosage and prior therapy with the drug, particularly within the last 3 months. Therapy with pentamidine, regardless of route of administration, should be administered cautiously in patients with or predisposed to diabetes or spontaneous hypoglycemia. Blood glucose should be monitored more closely during and for some time after pentamidine therapy.

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Hematologic toxicities have been associated occasionally with the parenteral use of pentamidine. Leukopenia and, less frequently, thrombocytopenia have been reported and may be severe (e.g., leukocyte count < 1000/mm3, platelet count < 20,000/mm3). Anemia, neutropenia, pancytopenia, and prolonged clotting time have occurred rarely. Therapy with pentamidine should be administered cautiously in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets, should be performed prior to and periodically during and after therapy. Marked depression of blood counts may be indication for withdrawal of pentamidine therapy.

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Acute and potentially fatal pancreatitis has been reported with parenteral use and, rarely, oral inhalation of pentamidine. Patients with a history of or known risk factors for pancreatitis, such as alcohol abuse or hypertriglyceridemia, should be monitored closely during therapy with pentamidine. Therapy should be discontinued at the first signs or symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.

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Parenteral use of pentamidine may be associated with nephrotoxicity, usually evidenced by elevations in BUN or serum creatinine concentrations. Azotemia has also been reported. Although pentamidine-induced nephrotoxicity is generally mild to moderate in severity and reversible following discontinuation of the drug, acute renal failure has occurred occasionally. Limited evidence suggests that nephrotoxicity may occur more frequently in patients with AIDS and may be accompanied by severe, sometimes life-threatening hyperkalemia. Therapy with pentamidine should be administered cautiously in patients with renal impairment. The need for dosage adjustments is uncertain. To minimize the risk of toxicity, patients should be adequately hydrated and use with other nephrotoxic agents should be avoided. Renal function and serum potassium levels should be closely monitored, and the dosing frequency reduced or therapy withdrawn if toxicity develops.

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Orally inhaled pentamidine is generally not associated with significant systemic toxicity due to limited absorption from the respiratory tract. However, detectable serum concentrations have been reported in some patients receiving chronic oral inhalation therapy, and systemic adverse effects have occasionally occurred. Therefore, when pentamidine is administered by oral inhalation, clinicians may want to heed the usual warnings and precautions associated with parenteral use of the drug.

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Orally inhaled pentamidine may induce bronchospasm and cough. Therapy with aerosolized pentamidine should be administered cautiously in patients with severe bronchospastic disease or a history of extensive smoking. Pretreatment with a beta-2 adrenergic bronchodilator prior to each dose of aerosolized pentamidine may be helpful in patients who experience respiratory symptoms from the medication.

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Parenteral use of pentamidine may cause elevated liver function tests. Therapy with pentamidine should be administered cautiously in patients with hepatic impairment. Serum transaminase, alkaline phosphatase, and bilirubin levels should be measured periodically, and the dosing frequency reduced or therapy withdrawn if significant elevations develop.

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Orally inhaled pentamidine is generally not associated with significant systemic toxicity due to limited absorption from the respiratory tract. However, detectable serum concentrations have been reported in some patients receiving chronic oral inhalation therapy, and systemic adverse effects have occasionally occurred. Therefore, when pentamidine is administered by oral inhalation, clinicians may want to heed the usual warnings and precautions associated with parenteral use of the drug.

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