Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.
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PMID:Zidovudine update: 1990. 219 18

A therapeutic committee was established in Toulouse Regional University Hospital in order to prescribe zidovudine in patients suffering from AIDS. Using an informatic card, the side effects were evaluated in the 125 patients treated by Zidovudine since the creation of the Committee (from July 1987 to January 1989). Zidovudine was prescribed from May 1987 to June 1988 at the total dose of 1,200 mg daily from June 1988 at 900 mg daily. The most frequent side effects were hematologic: zidovudine used alone (or associated with non hematotoxic drugs) elicited in 21.2% of patients a neutropenia (defined as a number of neutrophils less than 1,000/mm3), in 2.4% anaemia (haemoglobin less than or equal to 9 g/100 ml) and in 4.8% neutropenia associated with anaemia. When zidovudine was administered with hematotoxic drugs, neutropenia, anaemia or the association of both were observed in 12.0%, 3.2% and 2.4% of patients respectively. These hematologic side effects were always regressive after drug cessation. However, it is important to underline the low incidence of hematological side effects on red cells of zidovudine in the present study. This result is unexpected. The other side effects of Zidovudine (used alone) did not led to modification in drug treatment: gastrointestinal disturbances (30.4%), headaches (16.8%), insomnia (13.6%), somnolence (6.4%).... These side effects appeared during the four first months and decreased with the continuation of drug treatment. Their imputation was difficult to define and differentiate to evolution of the disease.
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PMID:[Evaluation of the pharmacovigilance follow-up of zidovudine]. 226 33

To determine the compliance and tolerance with zidovudine (azidothymidine or AZT) therapy among poor, minority, and intravenous drug-using patients, data were collected on all AIDS and ARC patients followed for at least 4 weeks in a New York City Human Immunodeficiency Virus clinic. Ninety-nine patients received zidovudine, of whom 75% were males, 92% were minorities, and 59% had a history of intravenous drug use. Of the 99 patients, 72 had AIDS and 27 had ARC with T-helper (CD4) lymphocytes less than or equal to 500 mm3. Eighty-seven of the 99 patients (88%) were compliant with zidovudine therapy. Fifty-seven percent of these had at least one adverse drug reaction requiring dose reduction (44%) or cessation (13%). Adverse reactions were similar to those reported in other populations with HIV-related illness, although headache and nausea were less common. Twenty opportunistic infections (OIs) or HIV-related malignancies occurred in 15 of 82 (18%) patients who were on zidovudine for at least 4 weeks (7.6 OIs/1,000 patient weeks). Seven of the 82 died (9%), compared to 9 of the 17 patients (53%) who did not complete 4 weeks of zidovudine therapy (p less than 0.05). There were no significant differences in any of these measures when intravenous drug users were compared with other risk groups. We conclude that zidovudine can be administered to intravenous drug users and others in an inner city clinic with acceptable compliance and tolerance.
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PMID:Zidovudine therapy in an inner city population. 238 64

The purine analog 2',3'-dideoxyinosine (ddI), which has anti-retroviral activity in vitro was administered for up to 42 weeks to 26 patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex (ARC). Ten of these individuals were AZT-intolerant. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid (CSF). Comparatively little evidence of an effect against human immunodeficiency virus (HIV) was seen at the lowest four doses. However, patients in the four highest dose groups (ddI at 1.6 milligrams per kilogram intravenously and then greater than or equal to 3.2 milligrams per kilogram orally at least every 12 hours or higher) had increases in their circulating CD4+ T cells (P less than 0.0005), increased CD4/CD8 T cell ratios (P less than 0.01), and, where evaluable, more than an 80% decrease in serum HIV p24 antigen (P less than 0.05). The patients also had evidence of improved immunologic function, had reduced viremic symptomatology, and gained a mean of 1.6 kilogram with these comparatively infrequent dosing schedules (every 8 or 12 hours). The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release) and mild headaches and insomnia. These results suggest that serious short-term toxicity at therapeutic doses is not an inherent feature in the profile of agents with clinical anti-HIV activity. Further controlled studies to define the safety and efficacy of this agent may be worth considering.
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PMID:In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine. 250 40

Zidovudine (azidothymidine) is a thymidine analogue antiretroviral drug active against human immunodeficiency virus (HIV). In acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients, orally and intravenously administered zidovudine is effective in reducing the incidence of opportunistic infections and neoplasms, increasing helper T lymphocyte numbers, and improving survival rates and quality of life. Adverse effects include serious haematological abnormalities and severe headache, abdominal discomfort, nausea, myalgia and insomnia. In addition, neutropenia and other anaemias frequently limit zidovudine therapy and may result in a need for multiple blood transfusions, dose reductions or withdrawal of the drug. However, despite these problems and the lack of information about some aspects of zidovudine use, zidovudine provides a major hope for HIV-infected patients, and it has rapidly become the standard therapy for improving the quality and duration of the lives of AIDS and ARC patients.
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PMID:Zidovudine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. 266 Nov 94

Zidovudine delays the progression of infection and prolongs the survival of human immunodeficiency virus (HIV)-infected patients, but these benefits are limited by dose-related toxicity and the cost of the drug. Dipyridamole, in micromolar concentrations, acts synergistically with zidovudine, reducing the anti-HIV 95% inhibitory concentration of zidovudine 5- to 10-fold in vitro. We sought to establish a well-tolerated dose of dipyridamole for use in combination with zidovudine and to detect clinically significant pharmacokinetic interactions. Both objectives are essential for planning studies of the efficacy of the zidovudine-dipyridamole combination. Eleven asymptomatic HIV-infected subjects (median CD4+ cell count, 311 cells per mm3), 10 of whom had been on zidovudine at 500 mg/day for at least 6 months, were admitted to the study. Zidovudine pharmacokinetics were measured on day 1. Dipyridamole was then begun at 600 mg/day (subjects 1 to 3) or 450 mg/day (subjects 4 to 11), and zidovudine and dipyridamole pharmacokinetics were measured on day 5. All subjects given 600 mg of dipyridamole per day developed headache or nausea, or both. Six of eight subjects given dipyridamole at 450 mg/day developed headache or mild nausea that resolved after a median of 2 days. The area under the zidovudine concentration-time curve was not significantly different on day 1 in comparison with that on day 5 (P = 0.11). Symptoms were significantly correlated with the maximum zidovudine concentrations, which were achieved when dipyridamole was dosed concomitantly (p = 0.03). Total (free and protein-bound) dipyridamole trough concentrations were near those demonstrating synergy with zidovudine against HIV in vitro. Dipyridamole was highly protein bound, with a median free/total dipyridamole ratio of 0.7%; the percent free/total dipyridamole ratio was inversely correlated with alpha 1 acid glycoprotein concentrations (r2 =0.66). Results of the study indicate that adjustment of the zidovudine dose was not required to achieve equivalent zidovudine concentrations when zidovudine was administered in combination with dipyridamole at the doses studied. In the short study described here, the zidovudine-dipyridamole combinations was well tolerated in asymptomatic HIV-infected subjects after the occurrence of mild transient symptoms.
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PMID:Effect of dipyridamole on zidovudine pharmacokinetics and short-term tolerance in asymptomatic human immunodeficiency virus-infected subjects. 806 34

Seventeen HIV-1-infected individuals were given AZT (100 mg tid) and ddC (0.375 mg tid) for consecutive periods of four weeks each and for total periods ranging from 8 to 32 weeks (median 17). Thirteen patients were offered AZT/ddC after having received other anti-retroviral combinations containing AZT, whereas in four it was used as front therapy. Before and after AZT/ddC, the median CD4 cell count changed from 184 to 164/uL (p NS), and the median body weight from 60 to 61 kg (p NS). Increases in hematological parameters were observed in patients previously exposed to AZT. In eight patients the side effects of AZT (gastrointestinal intolerance, cephalalgia and fever) disappeared when switched to ddC, whereas in one a reversible peripheral neuropathy ensued. The dosages of AZT/ddC used in this trial were well tolerated.
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PMID:[Sequential dideoxycytidine and zidovudine in advanced HIV-1 infection. Phase II study]. 839 11

Ten HTLV-I-associated myelopathy (HAM) patients (four men and six women aged 38 to 58 years) with Expanded Disability Status Scale (EDSS) scores ranging from 4.0 to 8.5 entered an open-label zidovudine study. A high-dosage induction (2 g/d for 4 weeks) was followed by 1 g/d for 20 weeks. Five patients were natives of the Caribbean island Hispaniola, and one each was from Colombia, Cuba, El Salvador, Jamaica, and the United States; all were positive by polymerase chain reaction, and nine had positive Western immunoblots for HTLV-I. Side effects included anxiety, insomnia, gastric upset, anorexia, and loss of taste. Preexisting leg cramps were increased in two and headaches in one. Hemoglobin decreased from a mean of 13.5 to 11.8 g/dl and the hematocrit from 40.7% to 34.9% at 8 weeks, and then stabilized. Neutropenia appeared regularly but did not necessitate drug withdrawal. Mean EDSS scores changed little for the group as a whole, but the seven ambulatory patients improved objectively, with their scores dropping from 5.5 to 4.0 and none worsening. Timed gait improved by at least 50%. Following withdrawal, four of the five who had improved regressed. Zidovudine appears to be safe in subjects with HAM who have no other major health problems and should be investigated further.
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PMID:High-dose zidovudine induction in HTLV-I-associated myelopathy: safety and possible efficacy. 841 77

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.
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PMID:Zidovudine toxicity. Clinical features and management. 848 Dec 17

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.
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PMID:A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease. 929 87


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