Chemical structure of didasonine.
Find information on thousands of medical conditions and prescription drugs.

Didanosine

Didanosine (2'-3'-dideoxyinosine, ddI) is sold uner the trade names Videx® and Videx EC®. It is a reverse transcriptase inhibitor, effective against HIV and usually used in combination with other antiviral drug therapy as part of highly active antiretroviral therapy (HAART). more...

Home
Diseases
Medicines
A
B
C
D
Dacarbazine
Dactinomycin
Dalmane
Danazol
Dantrolene
Dapoxetine
Dapsone
Daptomycin
Daraprim
Darvocet
Darvon
Daunorubicin
Daunorubicin
Daypro
DDAVP
Deca-Durabolin
Deferoxamine
Delsym
Demeclocycline
Demeclocycline
Demerol
Demulen
Denatonium
Depakene
Depakote
Depo-Provera
Desferal
Desflurane
Desipramine
Desmopressin
Desogen
Desogestrel
Desonide
Desoxyn
Desyrel
Detrol
Dexacort
Dexamethasone
Dexamfetamine
Dexedrine
Dexpanthenol
Dextran
Dextromethorphan
Dextromoramide
Dextropropoxyphene
Dextrorphan
Diabeta
Diacerein
Diacetolol
Dial
Diamox
Diazepam
Diazoxide
Dibenzepin
Diclofenac
Diclohexal
Didanosine
Dieldrin
Diethylcarbamazine
Diethylstilbestrol
Diethyltoluamide
Differin
Diflucan
Diflunisal
Digitoxin
Digoxin
Dihydrocodeine
Dihydroergotamine
Dihydrotachysterol
Dilantin
Dilaudid
Diltahexal
Diltiazem
Dimenhydrinate
Dimercaprol
Dimetapp
Dimethyl sulfoxide
Dimethyltryptamine
Dimetridazole
Diminazene
Diovan
Dioxybenzone
Diphenhydramine
Diphenoxylate
Dipipanone
Dipivefrine
Diprivan
Diprolene
Diproteverine
Dipyridamole
Disulfiram
Disulfiram
Dizocilpine
Dobutamine
Docetaxel
Docusate sodium
Dofetilide
Dolasetron
Dolobid
Dolophine
Domperidone
Donepezil
Dopamine
Dopram
Doral
Doramectin
Doriden
Dornase alfa
Doryx
Dostinex
Doxapram
Doxazosin
Doxepin
Doxil
Doxil
Doxorubicin
Doxy
Doxycycline
Doxyhexal
Doxylamine
Drisdol
Drixoral
Dronabinol
Droperidol
Drospirenone
Duloxetine
Durabolin
Duragesic
Duraphyl
Duraquin
Dutasteride
Dv
Dyclonine
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z

History

Didanosine was developed by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan in the National Cancer Institute (NCI). Since the NCI cannot market a product, the National Institutes of Health (NIH) awarded a ten-year exclusive licensed to Bristol-Myers Squibb Co. (BMS) to market and sell ddI as Videx® tablets.

Didanosine became the second drug approved for the treatment of HIV infection in many other countries, including in the United States by the Food and Drug Administration (FDA) on Oct 9, 1991. Its FDA approval helped bring down the price of zidovudine (AZT), the initial anti-HIV drug.

Didanosine has weak acid stability and is easily damaged by stomach acid. Therefore, the original formula approved by the FDA used chewable tablets that included an antacid buffering compound to neutralize stomach acid. The chewable tablets were not only large and fragile, they also were foul-tasting and the buffering compound would cause diarrhea. Although the FDA had not approved the original formulation for once-a-day dosing it was possible for some people to take it that way.

At the end of its ten-year license, BMS re-formulated Videx® as Videx EC® and patented that, which reformulation the FDA approved in 2000. The new formulation is a smaller capsule containing coated microspheres instead of using a buffering compound. It is approved by the FDA for once-a-day dosing. Also at the end of that ten-year period, the NIH licensed didanosine to Barr Laboratories under a non-exclusive license, and didanosine became the first generic anti-HIV drug marketed in the United States.

One of the patents for ddI will expire in the United States on 2006-08-29, but other patents extend beyond that time.

Mechanism of action

Didanosine (ddI) is a nucleoside analogue of adenosine. It differs from other nucleoside analogues, because it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Within the cell, ddI is, by cellular enzymes, phosphorylated to active metabolite of dideoxyadenosine triphosphate, ddATP. Like other anti-HIV nucleside analogs, it acts as a chain terminator by incorporation and inhibits viral reverse transcriptase by competing with natural dATP.

Oral absorption of ddI is fairly low (40%) but rapid. The half-life in plasma is only 30 minutes, but in intracellular environment more than 12 hours. An enteric-coated formulation is now marketed as well. The kidneys actively secrete didanosine, the amount being 20 % of the oral dose.

Adverse affects

The side effects of didanosine are mainly headache and nausea, but also peripheral neuropathy, insomnia, pancreatitis and alterations of liver functions have been reported. Drug resistance to didanosine does develop, though slower than to Zidovudine (AZT).

Read more at Wikipedia.org


[List your site here Free!]


Zidovudine and didanosine for HIV infection in children - Tips from Other Journals
From American Family Physician, 1/1/98 by Kathryn M. Andolsek

Most children with human immunodeficiency virus (HIV) infection acquire the infection by perinatal exposure. Zidovudine has been the recommended treatment for symptomatic children. Englund and associates conducted a multicenter double-blind investigation of the use of zidovudine, didanosine or both in previously untreated children with HIV infection.

A total of 839 children were assigned to treatment with zidovudine alone, didanosine alone or a combination of both zidovudine and didanosine. Follow-up was performed for a minimum of 104 weeks. Eight children were excluded from analysis because of refusal to participate following randomization or because they had already received more than six weeks of zidovudine therapy. Ninety percent of the children completed the study. The primary end point was the length of time until the first progression of HIV disease or until death. Disease progression was defined as the development of cancer, evidence of growth failure, the occurrence of two or more opportunistic infections, or evidence of two or more abnormalities of the central nervous system.

At the time of entry into the study, 450 (54 percent) of the children were under 30 months of age. Over 90 percent had acquired HIV perinatally. Only 29 children were born to mothers who had received zidovudine therapy prenatally. After the study had been under way for 23 weeks, interim analysis showed that patients receiving zidovudine alone had a relative risk of 0.61 for progression of HIV disease or death, compared with children treated with didanosine alone or combination therapy. Primary end points had been reached by 27 percent of the children receiving zidovudine, compared with 19 percent of those receiving didanosine and 18 percent of those receiving combination therapy. Because of this finding, the study arm with zidovudine alone was discontinued.

At the end of the study, children treated with didanosine alone had outcomes similar to those treated with combination therapy. The median follow-up was 32 months. However, compared with patients who received didanosine alone, those who received combination therapy had a 0.66 relative risk of serious anemia or neutropenia. This difference was primarily due to a lower risk of hematologic toxicity in older children receiving didanosine. A significant difference was not found among younger patients. No laboratory or clinically significant adverse effects necessitated cessation of therapy after the interim analysis.

At four weeks, [CD4.sup.+] counts had increased by a mean of 22 percent in the children receiving combination therapy, compared with an increase of 6 percent in those receiving didanosine alone. This improvement was not sustained, however. By week 96, the mean percentage of change in the [CD4.sup.+] count was similar in the two treatment groups.

In patients who initially tested positive for p24 antigen, the p24 antigen level after four weeks of treatment was 52 percent lower in the combination therapy group than in the didanosine group, but this benefit was not maintained after 24 weeks. Among patients who tested negative for p24 at the time of entry into the study, the length of time until the test became positive was similar in both treatment groups.

The authors conclude that the superiority of didanosine alone or the combination of didanosine and zidovudine over zidovudine alone in symptomatic children with HIV infection is a new and clinically important finding. Although combination antiviral regimens, especially those that include a protease inhibitor, may delay disease progression and prolong survival in adults with HIV infection, their efficacy has not previously been assessed in children. At the present time, the authors recommend didanosine alone as the initial therapy for HIV-infected children who have not previously received antiretroviral therapy.

Englund JA, et al. Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. N Engl J Med 1997;336:1704-12.

COPYRIGHT 1998 American Academy of Family Physicians
COPYRIGHT 2000 Gale Group

Return to Didanosine
Home Contact Resources Exchange Links ebay