victrelis with methadone

hello there,
as i posted already i will start soon my triple therapy with victrelis.
as my insurance only covers the victrelis i wonder about how does methadone interact with vic.
if i  have to in or decrease my metadone dose i dont care,but im worried a little that methadone
can make the vic less effective with the possibillity of ressistance.
i  know that telaprevir was tested with some methadone patients and it had no effect on methadone or contrary.
on the victrlis site the also only say no affect to victrelis from methadone,but maybe on methadone from vic.
ive seen that they are doing the same now in trial with vic,but wonder if anyone did vic with methadone so far.

i would be thankfull for some opinions

[HectorSF]

You may find this info helpful regarding how treatment tends to increase methadone levels.

This is from 46th European Association for the Study of the Liver (EASL) annual meeting Thursday, March 31, 2011

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About the HCV RESPOND-2 and HCV SPRINT-2 Studies

The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:

*   Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated
*   patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
*   48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).

In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).

7 DRUG INTERACTIONS

7.2 Methadone

PegIntron may increase methadone concentrations [see Clinical Pharmacology (12.3)]. The clinical significance of this finding is unknown; however, patients should be monitored for the signs and symptoms of increased narcotic effect.
------------------------------------------------------------------------------------------------------
12.3 Pharmacokinetics
Methadone

The pharmacokinetics of concomitant administration of methadone and PegIntron were evaluated in 18 PegIntron-naïve chronic hepatitis C subjects receiving 1.5 mcg/kg PegIntron subcutaneously weekly. All subjects were on stable methadone maintenance therapy receiving ≥40 mg/day prior to initiating PegIntron. Mean methadone AUC was approximately 16% higher after 4 weeks of PegIntron treatment as compared to baseline. In 2 subjects, methadone AUC was approximately double after 4 weeks of PegIntron treatment as compared to baseline [see Drug Interactions (7.2)].

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Your healthcare provider may need to monitor your therapy more closely if you take VICTRELIS with the following medicines. Talk to your doctor if you are taking or starting to take these medicines:
methadone (DOLOPHINE®)
-------------------------------------------------------------------------------------------------------
http://www.medicines.org.uk/emc/medicine/24768/SPC/victrelis%20200%20mg%20hard%20capsules/

Methadone - was not studied
Therapeutic monitoring is recommended when administering Victrelis with CYP3A4/5 substrates that have a narrow therapeutic window. Individual patients may require additional titration of their methadone dosage when Victrelis is started or stopped to ensure clinically effective blood levels.

Good luck with your treatment.!
Hector

[HectorSF]

You may find this info helpful regarding how treatment tends to increase methadone levels.

This is from 46th European Association for the Study of the Liver (EASL) annual meeting Thursday, March 31, 2011

----------------------------------------------------------------------------------------------------
About the HCV RESPOND-2 and HCV SPRINT-2 Studies

The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:

*   Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated
*   patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
*   48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).

In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).

7 DRUG INTERACTIONS

7.2 Methadone

PegIntron may increase methadone concentrations [see Clinical Pharmacology (12.3)]. The clinical significance of this finding is unknown; however, patients should be monitored for the signs and symptoms of increased narcotic effect.
------------------------------------------------------------------------------------------------------
12.3 Pharmacokinetics
Methadone

The pharmacokinetics of concomitant administration of methadone and PegIntron were evaluated in 18 PegIntron-naïve chronic hepatitis C subjects receiving 1.5 mcg/kg PegIntron subcutaneously weekly. All subjects were on stable methadone maintenance therapy receiving ≥40 mg/day prior to initiating PegIntron. Mean methadone AUC was approximately 16% higher after 4 weeks of PegIntron treatment as compared to baseline. In 2 subjects, methadone AUC was approximately double after 4 weeks of PegIntron treatment as compared to baseline [see Drug Interactions (7.2)].

-------------------------------------------------------------------------------------------------------
Your healthcare provider may need to monitor your therapy more closely if you take VICTRELIS with the following medicines. Talk to your doctor if you are taking or starting to take these medicines:
methadone (DOLOPHINE®)
-------------------------------------------------------------------------------------------------------
http://www.medicines.org.uk/emc/medicine/24768/SPC/victrelis%20200%20mg%20hard%20capsules/

Methadone - was not studied
Therapeutic monitoring is recommended when administering Victrelis with CYP3A4/5 substrates that have a narrow therapeutic window. Individual patients may require additional titration of their methadone dosage when Victrelis is started or stopped to ensure clinically effective blood levels.

Good luck with your treatment.!
Hector

[rexx73]

thanks a lot.
so i think i not have to worry to much about that.maybe i have to adjust my methadone dosage,but thats what i anyway expected.

[rexx73]

id like to bump this topic up.
does anyone know some poeple on methadone who doing the victrelis therapy?
i cant find some infos about less effectiness of victrelis when using methadone.
but do you poeple here think that it is a risk going for victrelis insteat of incivek.

[willbb]

Methadone will have no effect on the concentration of either Vic or Inci..so this factor should not influence your desicion

Hector has pointed out that Methadone concentration is somewhat increased with Vic.however  according to the Inci labeling it has a reduction of concentration effect.

.http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf

Concentration of methadone was reduced when co-administered with Incivek. No adjustment of methadone dose is required when initiating co-administration of Incivek.However clinical monitoring is recommended as the dose of methadone during maintenance therapy may be needed to be adjusted.

Good luck with whichever you choose..
Will

[rexx73]

thanks for your opinion on this.

i think i go with vic because i cant eat the fatty food with incivek.

here in europe the only say you have to eat some food with incivek(here we say incivo)but nothing about fat,so iam curious about this.
is the fat really important when using incivek?