Zidovudine dosing

Maintenance dose - When the desired response is attained, titrate the dose to maintain the response based on factors such as variations in zidovudine dose and the presence of intercurrent infectious or inflammatory episodes. If hemoglobin exceeds 13 g/dL, stop the dose until hemoglobin drops to 12 g/dL. 

Space zidovudine doses evenly around the clock... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

Fischl MA, Richman DD, Saag M, Meng TC, Squires KE, Holden-Wiltse J, Meehan PM (1997) Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-alpha2a in patients with HIV. J Acquit Immune Deflc Syndr Hum Retrovirol 16 247-253... 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

Dideoxyeytidine (DDC, zaleitabine), a nueleoside analogue that also inhibits reverse transeriptase, is more active than zidovudine in vitro, and (unlike zidovudine) does not suppress erythropoiesis. DDC is not without toxieity, however, and a severe peripheral neiuotoxicity, which is dose-related, has been reported. The chemical... 

Oral azoles are associated with significant interactions, particularly due to cytochrome P-450 isoenzymes. Medications that interact with azoles include warfarin, phenytoin, theophylline, rifampin, cyclosporine, and zidovudine. For patients receiving only a few doses, these interactions do not pose a significant risk. These interactions may pose a risk for patients receiving long-term suppressive therapy for recurrent infections. 

The answer is e. (Hardman, p 1206. Katzang, p 833J A major adverse effect of zidovudine is bone marrow depression that appears to be dose-and duration-dependent. The severity of the disease and a low CD4 count contribute to the bone marrow depression. 

Treatment of anemia related to zidovudine therapy in HIV-infected patients To elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients when the endogenous erythropoietin level is less than or equal to 500 milliunits/mL and the dose of zidovudine is less than or equal to 4200 mg/week. Treatment of anemia in cancer patients on chemotherapy Jreatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. It is intended to decrease the need for transfusions in patients who will be receiving chemotherapy for a minimum of 2 months. 

Initial dose - For patients with serum erythropoietin levels 500 milliunits/mL or less who are receiving a dose of zidovudine 4,200 mg/week or less, the recommended starting dose is 100 units/kg as an IV or subcutaneous injection 3 times/week for 8 weeks. 

Adults (IV) - Recommended IV dose is 1 mg/kg infused over 1 hour. Administer this dose 5 to 6 times daily (5 to 6 mg/kg/day). Patients should receive zidovudine IV infusion only until oral therapy can be administered. The IV dosing regimen equivalent to the oral administration of 100 mg every 4 hours is approximately 1 mg/kg IV every 4 hours. Avoid rapid infusion or bolus... 

Maternal dosing (IV) - During labor and delivery, administer IV zidovudine at 2 mg/kg (total body weight) over 1 hour followed by a continuous IV infusion of 1 mg/kg/h (total body weight) until clamping of the umbilical cord. 

Neonatal dosing (IV) - Neonates unable to receive oral dosing may be given zidovudine IV at 1.5 mg/kg, infused over 30 minutes, every 6 hours. 

Hepatic function impairment- Because zidovudine is primarily eliminated by hepatic metabolism, a reduction in the daily dose may be necessary in these patients. Frequent monitoring for hematologic toxicities is advised. 

Renal function Impairment Because it is a fixed-dose combination, do not prescribe lamivudine/zidovudine for patients requiring dosage adjustment, such as those with reduced renal function (Ccr less than 50 mL/min) or those experiencing dose-limiting adverse events. 

Hepatic function impairment A reduction in the daily dose of zidovudine may be necessary in patients with mild to moderate hepatic function impairment or liver cirrhosis. Because lamivudine/zidovudine is a fixed-dose combination that cannot be adjusted for this patient population, it is not recommended for patients with impaired hepatic function. 

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. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

---