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Effects of 2 rounds of AZT on newborn with street drugs at toxic levels

Here are the facts of this case: Adoptive child born to street drug using mom with 5 street drugs at toxic levels at birth, including: Methadone, cocaine, heroin, methamphetamines, marijuana and admitted to drinking wine. The infant has been sed...
by Dianne L in Campden, Ontario, Canada, 12/28/2005

Zidovudine side effects

Hi. My names is André I'm a Pharmaceutical Science student. I have to do a final college project and i choose a way to reduce zidovudine's side effects. For that, I want to know what's the metabolite cause anemia, granulocytopenia and leucopenia... Th...
by Melo, André da Rocha in Santos, São Paulo, Brazil, 03/09/2006

(Azidothymidine, AZT)

Zidovudine (Retrovir)
Azidothymidine (Retrovir)
AZT (Retrovir)
(zye- DOH-vyou-deen, ah- zee-doh- THIGH-mih-deen)
Pregnancy Category: C Apo-Zidovudine Novo-AZT Retrovir (Rx)

Classification: Antiviral

See Also: See also Antiviral Drugs and Anti-Infective Drugs .

Action/Kinetics: The active form of the drug is AZT triphosphate, which is derived from AZT by cellular enzymes. AZT triphosphate competes with thymidine triphosphate (the natural substrate) for incorporation into growing chains of viral DNA by retroviral reverse transcriptase. Once incorporated, AZT triphosphate causes premature termination of the growth of the DNA chain. Low concentrations of AZT also inhibit the activity of Shigella, Klebsiella, Salmonella, Enterobacter, Escherichia coli and Citrobacter although resistance develops rapidly. Rapidly absorbed from the GI tract and is distributed to both plasma and CSF. Peak serum levels: 0.1-1.5 hr. t 1/2: approximately 1 hr. Metabolized rapidly by the liver and excreted through the urine.

Uses: PO: Initial treatment of HIV-infected adults who have a CD 4 cell count of 500/mm 3 or less. Superior to either didanosine or zalcitabine monotherapy for initial treatment of HIV-infected clients who have not had previous antiretroviral therapy. To prevent HIV transmission from pregnant women to their fetuses. For HIV-infected children over 3 months of age who have HIV-related symptoms or are asymptomatic with abnormal laboratory values indicating significant immunosuppression. In combination with zalcitabine in selected clients with advanced HIV disease (CD 4 cell count of 300 cells/mm 3 or less).
IV: Selected adults with symptomatic HIV infections who have a history of confirmed Pneumocystis carinii pneumonia or an absolute CD 4 (T 4 helper/inducer) lymphocyte count of less than 200 cells/mm 3 in the peripheral blood prior to therapy.

Contraindications: Allergy to AZT or its components. Lactation.

Special Concerns: Use with caution in clients who have a hemoglobin level of less than 9.5 g/dL or a granulocyte count less than 1,000/mm 3. AZT is not a cure for HIV; thus, clients may continue to acquire opportunistic infections and other illnesses associated with ARC or HIV. AZT has not been shown to reduce the risk of HIV transmission to others through sexual contact or blood contamination.

Side Effects: Adults. Hematologic: Anemia (severe), granulocytopenia. Body as a whole: Headache, asthenia, fever, diaphoresis, malaise, body odor, chills, edema of the lip, flu-like syndrome, hyperalgesia, abdominal/chest/back pain, lymphadenopathy. GI: Nausea, GI pain, diarrhea, anorexia, vomiting, dyspepsia, constipation, dysphagia, edema of the tongue, eructation, flatulence, bleeding gums, mouth ulcers, rectal hemorrhage. CNS: Somnolence, dizziness, paresthesia, insomnia, anxiety, confusion, emotional lability, depression, nervousness, vertigo, loss of mental acuity. CV: Vasodilation, syncope, vasculitis (rare). Musculoskeletal: Myalgia, myopathy, myositis, arthralgia, tremor, twitch, muscle spasm. Respiratory: Dyspnea, cough, epistaxis, rhinitis, pharyngitis, sinusitis, hoarseness. Dermatologic: Rash, pruritus, urticaria, acne, pigmentation changes of the skin and nails. GU: Dysuria, polyuria, urinary hesitancy or frequency. Other: Amblyopia, hearing loss, photophobia, severe hepatomegaly with steatosis lactic acidosis, change in taste perception, hepatitis, pancreatitis, hypersensitivity reactions, including anaphylaxis hyperbilirubinemia (rare), seizures.
Children. The following side effects have been observed in children, although any of the side effects reported for adults can also occur in children. Body as a whole: Granulocytopenia, anemia, fever, headache, phlebitis, bacteremia. GI: N&V, abdominal pain, diarrhea, weight loss. CNS: Decreased reflexes, nervousness, irritability, insomnia, seizures. CV: Abnormalities in ECG, left ventricular dilation, CHF, generalized edema, cardiomyopathy S 3 gallop. GU: Hematuria, viral cystitis

Overdose Management: Symptoms: N&V. Transient hematologic changes. Headache, dizziness, drowsiness, confusion, lethargy. Treatment: Treat symptoms. Hemodialysis will enhance the excretion of the primary metabolite of AZT.

Drug Interactions: Acetaminophen / Risk of granulocytopenia Adriamycin / Risk of cytotoxicity, nephrotoxicity, or hematologic toxicity Dapsone / Risk of cytotoxicity, nephrotoxicity, or hematologic toxicity Flucytosine / Risk of cytotoxicity, nephrotoxicity, or hematologic toxicity Fluconazole / AZT Levels Ganciclovir / Risk of hematologic toxicity Interferon alfa / Risk of hematologic toxicity Interferon beta-1b / AZT serum levels Phenytoin / Levels of phenytoin may , , or remain unchanged; also, AZT excretion Probenecid / Biotransformation or renal excretion of AZT flu-like symptoms, including myalgia, malaise or fever, and maculopapular rash Rifampin / AZT levels Trimethoprim / AZT serum levels Vinblastine / Risk of cytotoxicity, nephrotoxicity, or hematologic toxicity Vincristine / Risk of cytotoxicity, nephrotoxicity, or hematologic toxicity

How Supplied: Capsule: 100 mg; Injection: 10 mg/mL; Syrup: 50 mg/5 mL; Tablet: 300 mg

?Capsules, Syrup Symptomatic HIV infections.
Adults: 100 mg (one 100-mg capsule or 10 mL syrup) q 4 hr around the clock (i.e., total of 600 mg daily).
Asymptomatic HIV infections.
Adults: 100 mg q 4 hr while awake (500 mg/day); Pediatric, 3 months-12 years, initial: 180 mg/m 2 q 6 hr (720 mg/m 2/day, not to exceed 200 mg q 6 hr).
Prevent transmission of HIV from mothers to their fetuses (after week 14 of pregnancy).
Maternal dosing: 100 mg 5 times a day until the start of labor. During labor and delivery, AZT IV at 2 mg/kg over 1 hr followed by continuous IV infusion of 1 mg/kg/hr until clamping of the umbilical cord. Infant dosing: 2 mg/kg PO q 6 hr beginning within 12 hr after birth and continuing through 6 weeks of age. Infants unable to take the drug PO may be given AZT IV at 1.5 mg/kg, infused over 30 min q 6 hr.
In combination with zalcitabine.
Zidovudine, 200 mg, with zalcitabine, 0.75 mg, q 8 hr.
1-2 mg/kg infused over 1 hr. The IV dose is given q 4 hr around the clock only until PO therapy can be instituted. Dosage adjustment may be necessary due to hematologic toxicity.

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