Tenofovir Cidofovir

Adefovir, cidofovir, tenofovir Radiographic contrast media... 

CIDOFOVIR TENOFOVIR t adverse effects t plasma levels competition for renal excretion via organic anion transporter Monitor renal function weekly... 

Oats Sitagliptin, cimetidine, ibuprofen, quinapril, indapamide, adefovir, cidofovir, tenofovir, cephalosporin, torsemide... 

Acute tubular necrosis Aminoglycoside antibiotics Radiographic contrast media Cisplatin, carboplatin Amphotericin B Cyclosptenofovir Pentamidine Foseamet Zoledronate... 

However, acyclic nucleotide analogs (acyclic nucleoside phosphonates) have been developed, which carry one phosphonate moiety and require only the two subsequent phosphorylation steps (De Clercq et al. 1978). Independent of virus-encoded kinases, they display a broader spectrum of efficacy. This class comprises important drugs against HIV (tenofovir) and HBV (adefovir, tenofovir), as well as cidofovir, which is approved for use against CMV retinitis, but also displays an exceptionally broad efficacy profile against many herpesviruses, adenovirus, poxviruses, and papillomaviruses (De Clercq and Holy 2005). 

The prototype member of the ANPs is (5)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine (HPMPA) (Fig. 2), first described for its broad-spectrum anti-DNA virus activity in 1986 (De Clercq et al. 1986). Then followed by the description of various other acyclic nucleoside phosphonates in 1987 (De Clercq et al. 1987). At present three acyclic nucleoside phosphonates have been licensed for clinical use cidofovir, adefovir, and tenofovir (Fig. 2). 

After me ANPs (i.e., cidofovir, adefovir, and tenofovir) have been released (intra-or extraceUularly) from their prodrugs through the mtervention of infra- or extracellular esterases, they need only two phosphorylation steps to be converted to their active metabolites (i.e., HPMPCpp, PMEApp, and PMPApp), which will then compete with the natural substrates (dCTP for HPMPCpp, and dATP for PMEApp and PMPApp) for incorporation into me viral DNA (Fig. 6a). 

Other drugs that are commonly implicated in causing ARF include acyclovir, adefovir, carboplatin, cidofovir, cisplatin, foscarnet, ganciclovir, indinavir, methotrexate, pentamidine, ritonavir, sulfinpyrazone, and tenofovir.45... 

Drugs eliminated by the kidneys Coadministration of tenofovir with drugs that are eliminated by active tubular secretion may increase serum concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, and valganciclovir. Drugs that decrease renal function also may increase serum concentrations of tenofovir. 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

DeClercq E. 2003. Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir in treatment of DNA virus and retrovirus infections. Clin Microbiol Rev. 16 ... 

Increased nephrotoxicity with tenofovir, cidofovir, acyclovir, cyclosporine, gancyclovir... 

Increased risk of nephrotoxicity with cidofovir, aminoglycosides, carbopla-tin, cisplatin, clofarabine, efavirenz/emtricitabine/tenofovir, tacrolimus... 

Increased nephrotoxicity with cidofovir, aminoglycosides, carboplatin, cisplatin, clofarahine, efavirenz/emtricitahine/tenofovir, gallium, tenofovir... 

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS -aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - cidosporin, tacrolimus 3. ANTIFUNGALS-amphotericin, 4. ANTIPROTOZOALS-pentamidine 5. ANTIVIRALS - cidofovir, foscarnet sodium, tenofovir Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

Tenofovir (TDF) Viread 300 mg tablet fV aminoglycosides, acyclovir, famciclovir, ganciclovir, valacyclovir, cidofovir... 

Acute tubular necrosis (exogenous toxins) Aminoglycosides, amphotericin, cisplatin, radiocontrast agents, methoxyflurane, outdated tetracyclines, cephalosporins, mithramycin, calcineurin inhibitors, pentamidine, IVIG, ifosfamide, zoledronate, cidofovir, adefovir, tenofovir FENa>2%, UOsm <350, urinary sediment contains granular casts, renal epithelial cells... 

Tenofovir is actively secreted by human organic anion transporter 1 (hOATl) in the kidneys. Therefore, the manufacturers suggest that if it is given with other drugs that are also secreted by this renal transporter, such as cidofovir, increased le vel s of tenofovir or the other drug could result. In the UK, they specifically recommend that tenofovir and cidofovir are not given together, unless clearly necessary, when renal function should be monitored weekly. ... 

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