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FTC - A NEW NUKE COMING SOON

FTC, also known by its generic name emtricitabine, will be Gilead's second anti-HIV drug. Andrew Balkin explains how it works.

DRUG NAME:	Emtricitabine (also known as FTC).
DRUG CLASS:	Nucleoside reverse transcriptase inhibitor (NRTI), also known as "nukes" or nucleoside analogues.
BRAND NAME:	Emtriva

     

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HOW EMTRICITABINE WORKS:
Emtricitabine is currently in Phase III clinical trials for the treatment of HIV in treatment naive patients and stable treatment-experienced patients. It is chemically similar to lamivudine (3TC) and, in the laboratory has been shown to be 4-10 times more potent.

Last September a New Drug Application was submitted to the US Food and Drug Administration for marketing approval of emtricitabine in the treatment of HIV. An application for European licence was submitted in December 2002.

The drug also inhibits the hepatitis B virus and trials are currently being conducted in the disease area. Emtricitabine was originally being developed by Triangle Pharmaceuticals, but the company was acguired by Gilead in December 2002. Gilead will seek licensing approval for emtricitabine - it may be granted approval by the autumn 2003.

Gilead is also looking to eventually produce a single once-daily pill that will co-formulate two anti-HIV drugs, emtricitabine and tenofovir (DF).

COMBINATION THERAPY:
Emtricitabine must be taken as part of an antiretroviral combination regime. Studies have considered interactions with other antiretrovirals - no clinically significant interactions were found.

The use of emtricitabine and lamivudine in combination for the treatment of HIV cannot be recommended currently.

DOSING:
Emtricitabine will be available in 200mg hard white capsules. This is the optimum dose that has currently been used on hundreds of people in clinical trials. Emtricitabine can be taken with or without food.

STORAGE:
Emtricitabine should be stored at room temperature.

DOSING RESTRICTIONS:
Once daily dosing with emtricitabine is likely. The drug stays in cells for a significant amount of time; its intracellular half-life is 39 hours.

People with impaired kidney function may require dosing adjustments: emtricitabine caused abnormal renal function in two people during clinical trials.

SIDE EFFECTS:
No serious or dose-related toxicities were seen in early clinical trials of emtricitabine monotherapy.

A small percentage of people in clinical trials experienced some side effects with emtricitabine, including:

• Nausea;
• Vomiting;
• Diarrhoea;
• Pharyngitis (inflammation in the pharynx - behind the nose and mouth);
• Headache;
• Infection;
• Asthenia (lack of energy);
• Rhinitis;
• Cough.

PRE-EXISTING CONDITIONS:
Because of the minor renal side effects noted in clinical trials, careful monitoring and possible dose adjustment may be necessary for people with renal (kidney) impairment.

PAEDIATRIC USE:
In clinical trials, emtricitabine appears to be safe, effective and well tolerated by children.

A trial dose of 6mg/kg was used in a large paediatric study and results were similar to those achieved by adults on the 200mg dose.

USE DURING PREGNANCY:
There are no adequate and well-controlled studies on the use of emtricitabine in pregnant women. For this reason, emtricitabine should only be used during pregnancy if the benefits justify any potential risks.

EMTRICITABINE RESISTANT HIV:
The M184V mutation (associated with lamivudine-resistance) is the key resistance mutation for emtricitabine. However, studies show that when emtricitabine treatment fails, the M184V mutation is less likely to emerge than it is when lamivudine treatment fails.

Emtricitabine-resistant viruses were cross-resistant to lamivudine. However, they retained sensitivity to the other NRTIs (zidovudine, stavudine, tenofovir, abacavir, didanosine and zaicitabine). Emtricitabine also remained sensitive to all NNRTIs and all Pis.