Nephrotoxicity pentamidine

In summary, parenteral pentamidine administration for the treatment of PCP can be associated with the development of usually mild, reversible acute kidney injury. Compounding risk factors, of which volume depletion is the most important, are found in the majority of cases of pentamidine nephrotoxicity. There is no convincing evidence that the aerosol route of pentamidine administration for PCP prophylaxis results in nephrotoxicity. Hypocalcemia and hypomagnesemia with renal magnesium wasting, and particularly, hyperkalemia are seen with pentamidine therapy. 

Chua A BJ, Alpert El, Vaamonde CA. Risk factors for pentamidine nephrotoxicity in AIDS patients. Nat Kidney Found. 1989 19 A5 (abstract). 

Chua A BJ, Papendick R, Alpert H, Vaamonde CA. Pentamidine nephrotoxicity in the rat. Kidney international. 1990 37 478A. 

Perturbations in mono- and divalent cation renal handling have been reported in association with pentamidine administration. Several reports of hyperkalemia in association with pentamidine therapy have been recently published [132,134,136,137,167,168]. Lachaal and Venuto [132] in a retrospective review reported a very high incidence of hyperkalemia (5.1 to 8.7 mEq/ L) in 19 of 20 patients (95%). This incidence was greater than the 5% reported earlier [123], or the 24% reported subsequently [134] in 37 patients with AIDS, and was challenged as a possible overestimation [169]. The hyperkalemia usually correlates with the presence of decreased GFR [132,134]. In our clinical study [133] the mean serum potassium concentration tended to be higher in the AIDS patients that developed pentamidine nephrotoxicity than in those that did not (5.0+0.3 vs 4.3+0.2, respectively, p <0.055). No patient, however, had a serum potassium concentration higher than 6.0 mEq/L. Hyperkalemia induced-arrhythmias occur [170], and rarely may include cardiac arrest [171]. The hyperkalemia usually reversed on discontinuation of pentamidine, and although most patients required only conservative measures, occasionally dialysis was necessary [132]. 

An additive nephrotoxicity develops when pentamidine isethionate is administered with other nephrotoxic drugs (eg, aminoglycosides, vancomycin, or amphotericin B). An additive bone marrow depression occurs when the drug is administered with antineoplastic drugs or when the patient lias received radiation therapy recently. 

Foscarnet Pentamidine IV Increased risk of severe nephrotoxicity/hypocalcemia Monitor renal functiorVserum calcium... 

For pentamidine, side effects include hypotension, tachycardia, nausea, vomiting, severe hypoglycemia or hyperglycemia, pancreatitis, irreversible diabetes mellitus, elevated transaminases, nephrotoxicity, leukopenia, and cardiac arrhythmias. 

Drugs that may interact with foscarnet include nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine), pentamidine, and zidovudine. Foscarnet decreases serum levels of ionized calcium. Exercise particular caution when other drugs known to influence serum calcium levels are used concurrently. 

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

Foscarnet should not be used in combination with drugs that cause renal toxicity (e.g., acyclovir, aminoglycosides, amphotericin B, NSAIDs). Abnormal renal function has been noted when foscarnet is used with ritonavir or ritonavir and saquinavir. Pentamidine may increase the risk of nephrotoxicity, hypocalcemia, and... 

The primary adverse effect of intravenous cidofovir is a dose-dependent nephrotoxicity. Concurrent administration of other potentially nephrotoxic agents (eg, amphotericin B, aminoglycosides, nonsteroidal anti-inflammatory drugs, pentamidine, foscarnet) should be avoided. Prior administration of foscarnet may increase the risk of nephrotoxicity. Other potential side effects include uveitis, decreased intraocular pressure, and probenecid-related hypersensitivity reactions. Neutropenia and metabolic acidosis are rare. The drug caused mammary adenocarcinomas in rats and is embryotoxic. 

Pentamidine is a synthetic aromatic amidine it must be administered parenterally or by inhalation as it is unreliably absorbed from the gastrointestinal tract it does not enter the CSF. Given systemically it frequently causes nephrotoxicity, which is reversible acute hypotension and syncope are common esp-ecicdly after rapid i.v. injection. Pancreatic damage may cause h5q>oglycaemia due to insulin release. 

Antoniskis et al reported four cases of reversible acute kidney injury in patient with AIDS who received both intravenous pentamidine (for PCP) and amphotericin B (for systemic mycoses). Of note, nephrotoxicity did not develop in three AIDS patients treated with both TMP-SMZ and amphotericin B or in two patients who concomitantly received inhaled pentamidine and amphotericin B [160]. Reports of renal damage in patients receiving parenteral pentamidine for the treatment of non-HIV diseases continue. Reversible acute kidney injury and nephrotic syndrome were documented in a young child given pentamidine mesylate and an antimonial salt for the treatment of visceral leishmaniasis [161]. In Africa (Kenya) patients with visceral leishmaniasis have developed renal toxicity during prolonged treatment (1 to 10 months) with pentamidine [162]. 

Lachaal M, Venuto RC. Nephrotoxicity and hyperkalemia in patients with acquired immunodeficiency syndrome treated with pentamidine.The American journal of medicine. 1989 Sep 87(3) 260-3. 

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