Carbamazepine chemical structure
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Carbatrol

Carbamazepine (sold under the brand-names Biston®, Calepsin®, Carbatrol®, Epitol®, Equetro®, Finlepsin®, Sirtal®, Stazepine®, Tegretol®, Telesmin®, Timonil®) is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat schizophrenia and trigeminal neuralgia. more...

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Mechanisms

Carbamazepine and its derivatives' action mechanism is not well understood, but appears to be primarily through the inhibition of sodium channel activity.

Side-effects

Carbamazepine renders birth control pills ineffective.

Common side-effects include drowsiness, motor-coordination impairment and/or upset stomach. Taken every twelve hours, the Tegretol XR® or Carbatrol® preparations can greatly increase tolerability.

Less common side-effects include blurry or double vision and/or the temporary or mild loss of blood cells or platelets. In rare cases the latter can be life-threatening if unnoticed, so frequent blood tests are required during the first few months' use, followed by three or four tests per year. There are also reports of a bizarre auditory side-effect, whereby patients perceive musical notes about a semitone lower than their actual pitch (so middle C would be heard as the note B3 just below it, etc).

Oxcarbazepine, a derivative of carbamazepine, has fewer and less serious side-effects.

History

Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953. Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.

Carbamazepine was first marketed as a drug to treat trigeminal neuralgia in 1962. It has been used as an anticonvulsant in the UK since 1965, but only approved in the U.S. since 1974.

Read more at Wikipedia.org


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DELAVIRDINE - Rescriptor
From Research Initiative/Treatment Action!, 3/1/00

Delavirdine tablets are white, capsule-shaped and marked with "U 3761."

The US Food and Drug Administration (FDA) Advisory Committee split 4 in favor and 4 against granting accelerated approval to delavirdine.

November 22, 1996

"This pill-pushing madness has got to STOP! How many more HIV antibody positives are we going to allow to be poisoned by these chemical concoctions?"

--David Pasquarelli, December 24, 1996

The FDA grants accelerated approval for delavirdine for use in combination with other anti-HIV drugs. April 4, 1997

Also known as: DLV, delavirdine mesylate, BHAP, U-90152

Background and description. Delavirdine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), manufactured by Pharmacia & Upjohn. Recently Agouron Pharmaceuticals acquired the commercial rights to delavirdine. The drug was granted accelerated approval for use with other antiretroviral drugs by the FDA in April 1997.

Guidelines classification. The Panel on Clinical Practices for the Treatment of HIV Infection recommends delavirdine as an "alternative" NNRTI.

Dose. The recommended dose of delavirdine is 400 mg (four 100 mg tablets) 3 times a day. A dose can be dissolved in 3 ounces of water for ease of administration. Some studies currently use 600 mg twice a day.

Food restrictions. Delavirdine may be taken with or without food.

Storage. Delavirdine should be stored at a controlled room temperature of 68 [degrees] to 77 [degrees] F in a tightly closed container and protected from high humidity.

Side effects and toxicity. The most common side effect is a skin rash that usually lasts less than 2 weeks. In clinical studies, skin rash occurred in 18% of patients receiving the 400 mg dose of delavirdine 3 times a day. The rash tends to occur early, usually within 1 to 3 weeks after initiating delavirdine. Other side effects include headache, nausea, diarrhea, fatigue and elevation of liver enzymes. Of these, nausea is the most commonly reported.

Drug interactions. Delavirdine should not be taken with the following: alprazolam (Xanax), midazolam (Versed), triazolam (Halcion), carbamazipine (Carbatrol, Tegretol, Tegretol XR), phenobarbital, phenytoin (Dilantin), cisapride (Propulsid), cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), ranitidine (Zantac), rifampin (Rifadin, Rimactane) or rifabutin (Mycobutin). Antacids should be taken at least 1 hour before or after taking delavirdine because they can slow the absorption of delavirdine. Didanosine should be taken 1 hour before or after delavirdine. Delavirdine increases the blood levels of saquinavir (Fortovase), ritonavir (Norvir), indinavir (Crixivan) and nelfinavir (Viracept). Dosing adjustment may be required. No data with respect to its interaction with amprenavir (Agenerase) have been reported.

Resistance and cross-resistance. Resistance to delavirdine emerges rapidly in vitro and when used as monotherapy. Resistance resulting in treatment failure is commonly associated with mutations at positions 103 and 181. The mutation at position 103 causes cross-resistance with all other approved NNRTIs.

Clinical data. Delavirdine was approved on the basis of 3 studies: Pharmacia & Upjohn Study 0021, Study 0017 and ACTG 261. None of the combinations in any of these studies are capable of achieving maximal viral suppression and since resistance develops rapidly to delavirdine when used in suboptimal combinations, these studies showed little benefit from the use of delavirdine.

Subsequent research reported at the 5th Conference on Retroviruses and Opportunistic Infections (Chicago, 1998) compared delavirdine/zidovudine/lamivudine (Epivir) against zidovudine/lamivudine against delavirdine/zidovudine. At 24 weeks the triple-combination arm had a significantly greater reduction in viral load (2.25 log) than the other 2 arms. Similarly, the percentage of patients in that arm having viral loads less than 400 copies/mid was significantly greater (71% at week 24) than the other 2 arms. CD4 T cell increase in the triple-drug arm was 105 cells/[mm.sup.3] compared to 75 cells/[mm.sup.3] in the zidovudine/lamivudine arm and 3 cell/[mm.sup.3] in the delavirdine/zidovudine arm.

Patient assistance. Agouron offers a patient assistance program for those who qualify. For more information call 888.777.6637.

COPYRIGHT 2000 The Center for AIDS: Hope & Remembrance Project
COPYRIGHT 2000 Gale Group

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