Drug therapy zidovudine

Failure of antiretroviral drug therapy has been attributed to an interaction of carbamazepine with indinavir in a 48-year-old man taking indinavir, zidovudine, and lamivudine his HIV-RNA viral load became undetectable after less than 2 months and he developed a Herpes zoster infection (87). Lower doses of carbamazepine are also required during co-administration of ritonavir, as has been shown in two recent cases. 

Despite a prophylactic reduction in the dose of ciclosporin (100 mg/day) before antiretroviral treatment, a 40-year-old woman had an acute increase in ciclosporin trough concentrations (over 1000 ng/ml) and serum creatinine concentration (from 84 to 228 gmol/l) after taking zidovudine (600 mg/day), saquinavir (800 mg/day), and ritonavir (800 mg/day) for 11 days (289). Despite ciclosporin withdrawal, ciclosporin and creatinine blood concentrations remained high for over 10 days until triple drug therapy was withdrawn. Ritonavir was the most likely suspect. 

A variable-dose plasma concentration-controlled approach to combination antiretroviral therapy (zidovudine, lamivudine, and indinavir) has been compared with conventional fixed-dose therapy in 40 patients in a randomized, 52-week, open trial (6). Significantly more concentration-controlled recipients achieved the desired concentrations for aU three drugs there was a good response in 15 of 16 concentration-controlled recipients compared with nine of 17 conventional regimen recipients. However, there was no difference in the occurrence... 

In a comparison of changes in bone mineral density in 106 HIV-1 infected, antiretroviral drug-naive patients, who were randomized to zidovudine -i- lamivudine with either efavirenz n = 32) or lopinavir + ritonavir n = 74) for 96 weeks, the mean changes from baseline in total bone mineral density were -2.5% (lopinavir -I- ritonavir) and -2.3% (efavirenz) [79 . The authors concluded that loss of bone mineral density during antiretroviral drug therapy is independent of the drug regimen. 

Stavudine possesses several clinically significant interactions with other drugs. Although hydroxyurea enhances the antiviral activity of stavudine and didanosine, combination therapy that includes stavudine and didanosine, with or without hydroxyurea, increases the risk of pancreatitis. Combinations of stavudine and didanosine should not be given to pregnant women because of the increased risk of metabolic acidosis. Zidovudine inhibits the phosphorylation of stavudine thus, this combination should be avoided. 

Inpatients with no prior antiretroviral therapy, a randomized trial found atazanavir equivalent to efavirenz when both were part of a 3 drug combination including zidovudine and lamivudine another trial found atazanavir equivalent to nelfinavir when both were part of a 3 drug combination including lamivudine and stavudine... 

Drug Interactions According to the product label, interactions between Intron A and other drugs have not been fully evaluated. Caution should be exercised when administering Intron A therapy in combination with other potentially myelo-suppressive agents such as zidovudine. Concomitant use of alfa interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

Shafer RW, Kozal MI, Winters M, Iversen AKN, Katenstein DA, Ragni MV, et al. Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J Infect Dis 1994 169 722-729. 

After oral administration, lamivudine is rapidly absorbed, and its bioavailability is about 86%. Food slows down its absorption, and it is excreted unchanged in the urine. The drug crosses the placenta, and the transfer to placenta does not appear to be altered by zidovudine. Its concentrations are higher in the male genital tract in comparison with the circulation. In combination with other antiretroviral therapy, lamivudine is recommended for the treatment of HIV infection. It inhibits plasma HIV-1 RNA concentrations but resistance develops rapidly when used as monotherapy. 

Considerable neuromuscular involvement also occurs in patients with AIDS.47 100 Peripheral neuropathies, myopathies, and various CNS manifestations (dementia, other psychological manifestations) can occur directly from HIV infection or secondarily, due to some other opportunistic infection.31 85 100 Likewise, peripheral neuropathies are a common side effect of certain anti-HIV drugs (didanosine, stavudine, zal-citabine), and myopathies are a side effect of zidovudine therapy.63 Patients with HIV disease often have painful symptoms such as joint pain, back pain, and pain related to neuropathies and myopathies.100 Hence, HIV disease can often be regarded as a degenerative neuromuscular disorder from the standpoint of a rehabilitation professional. Therapists can therefore help improve function and decrease pain in patients with HIV infection and AIDS.1 33... 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Zidovudine i.s recommended for the management of adult patients with symptomatic HIV infection (AIDS or ARC) who have a history of confirmed Pneumocystis carinii pneumonia or an absolute CD4 (T4 or Th cell) lymphocyte count below 2(X)/mm before therapy. The hematological toxicity of the drug precludes its use in asymptomatic patients. Anemia and granulocytopenia are the most common toxic effects associated with AZT. 

Some ofthe classical antiviral drugs in HIV therapy are nucleoside derivatives, and they are called nucleoside reverse transcriptase inhibitors (NRTIs). Zidovudine... 

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