Daclatasvir Warning - Interactions CYP3A4

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16 September 2015 at 7:46 am #1296
Dr James
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@fixhepc
For those of you embarking on a journey with Daclatasvir please be aware that this medication is metabolised by an enzyme called CYP3A4.

There are some other medications that inhibit this enzyme (resulting in higher Daclatasvir levels) and other medications that induce (increase) this enzyme (resulting in lower Daclatasvir levels).

Dose reduction (to 30 mg) is suggested for people who are taking medications that are strong inhibitors of CYP3A4. Don’t worry if dose reduction is suggested, because the Daclatasvir is not metabolised as well you will probably still have higher than normal levels.

Inhibitors of CYP3A4 include (please note this is not an exhaustive list):
- Aminodarone
- Anastrozole
- Azithromzcin
- Cannabinoids
- Cimetidine
- Clarithromycin
- Clotrimazole
- Cyclosporine
- Danazol
- Delavirdine
- Dexamethasone
- Diethyldithiocarbamate
- Diltiazem
- Dirithyromycin
- Disulfiram
- Entacapone (high dose)
- Erythromycin
- Ethinyl estradiol
- Fluconazole
- Fluoxetine
- Fluvoaxamine
- Gestodene
- Grapefruit juice
- Indinavir
- Isoniazid
- Ketoconazole
- Metronidazole
- Mibefradil
- Miconazole
- Nefazodone
- Nelfinavir
- Nevirapine
- Norfloxacin
- Norfluoxetine
- Omeprazole
- Oxiconazole
- Paroxetine (weak)
- Propoxyphene
- Quinidine
- Quinine
- Quinupristine and dalfopristin
- Ranitidine
- Ritonavir
- Saquinavir
- Sertindole
- Sertraline
- Troglitazone
- Troleandomycin
- Valproic acid
This list includes common antidepressants, ingredients in the contraceptive pill and even Grapefruit Juice.

Here is the FDA overview on CYP3A4 – Check table 5 (in vivo)* – and note than a strong inhibitor is of course more of a worry than a weak one.

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm

* Studies that are in vivo (Latin for “within the living”) are those in which the effects of various biological entities are tested on whole, living organisms usually animals including humans, and plants as opposed to a partial or dead organism, or those done in vitro (“within the glass”)

YMMV
29 April 2016 at 7:30 am #16332
kimko57
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@kimko57
Cannabinoids are on the list,…… Drop the pipe boys and girls!!
29 April 2016 at 2:12 pm #16352
beaches
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@beaches
Thank you, Doctor James

So I guess I need to stay away from the GSE (grapefruit seed extract)

One question if I may; some medications are applied to the skin,for example Clotrimazole which is an anti fungal. Should treatments applied to the skin be avoided too?

Thank you

Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
29 April 2016 at 3:35 pm #16354
Dr James
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@fixhepc
Should treatments applied to the skin be avoided too?

No, there is typically very little absorption of topicals.

Yes estrogen patches and nicotine patches and fentanyl patches all prove this generalisation wrong!

YMMV
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