Triple therapy and simvastatin

Does anyone know if these are okay together?
My doc says its okay but I am reading differently.
Thanks so much.

[pooh55811]

You did not state which PI you will be using. Here is what I found for Incivek or Victrelis in combo with Pegasys, Ribavirin and Simvastatin. Both PIs are contraindicated. See below:


Incivek (teleprevir), Pegasys, Ribavirin, Simvastatin:

simvastatin ↔ telaprevir
Applies to: simvastatin, Incivek (telaprevir)

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 including telaprevir may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors and their pharmacologically active metabolites that are primarily metabolized by the isoenzyme. In 19 study subjects, administration of a single 20 mg dose of atorvastatin following pretreatment with telaprevir 750 mg every eight hours for 7 days increased the atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 10.6- and 7.9-fold , respectively, compared to administration alone. The interaction has also been reported in patients receiving atorvastatin, lovastatin, or simvastatin with other potent CYP450 3A4 inhibitors such as azole antifungal agents, macrolide antibiotics, HIV protease inhibitors, and nefazodone. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Due to the potential for severe interaction, concomitant use of atorvastatin, lovastatin, or simvastatin with telaprevir is considered contraindicated. Red yeast rice, which contains lovastatin, should also be avoided during treatment with telaprevir. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.


simvastatin ↔ peginterferon alfa-2a
Applies to: simvastatin, Pegasys (peginterferon alfa-2a)

MONITOR: The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

MANAGEMENT: Caution is advised during concomitant use of agents with neurotoxic effects. Patients should be monitored closely for symptoms of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Since the development of peripheral neuropathy may be dose-related for many drugs, the recommended dosages should generally not be exceeded. Consideration should be given to dosage reductions or immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If necessary, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, reduced dosages may be required.

http://www.drugs.com/interactions-check.php?drug_list=2009-0,2067-0,3328-15346,1806-1159



Victrelis, Pegasys, Ribavirin, Simvastatin:

simvastatin ↔ boceprevir

Applies to: simvastatin, Victrelis (boceprevir)

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 including boceprevir may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors and their pharmacologically active metabolites that are primarily metabolized by the isoenzyme. The interaction has been reported in patients receiving lovastatin or simvastatin with other potent CYP450 3A4 inhibitors such as azole antifungal agents, macrolide antibiotics, HIV protease inhibitors, and nefazodone. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: Due to the potential for severe interaction, concomitant use of lovastatin or simvastatin with boceprevir is considered contraindicated. Red yeast rice, which contains lovastatin, should also be avoided during treatment with boceprevir. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.


simvastatin ↔ peginterferon alfa-2a

Applies to: simvastatin, Pegasys (peginterferon alfa-2a)

MONITOR: The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

MANAGEMENT: Caution is advised during concomitant use of agents with neurotoxic effects. Patients should be monitored closely for symptoms of neuropathy such as burning, tingling, pain, or numbness in the hands and feet. Since the development of peripheral neuropathy may be dose-related for many drugs, the recommended dosages should generally not be exceeded. Consideration should be given to dosage reductions or immediate discontinuation of these medications in patients who develop peripheral neuropathy to limit further damage. If necessary, therapy should generally be reinstituted only after resolution of neuropathy symptoms or return of symptoms to baseline status. In some cases, reduced dosages may be required.

http://www.drugs.com/interactions-check.php?drug_list=2009-0,2067-0,1806-1159,3323-15313

[pooh55811]

To clarify:

Simvastatin is contraindicated with the use of Incivek or Victrelis.

[KathHall]

Thanks for the info. I will show my doc. Don't know which one yet waiting on biopsy in 2 weeks. Do I have any options  I was hoping for early unddest to only do 24 weeks with these meds. Thanks again.

[sandysf]

I like this site, you have to register, but it is free and easy to look up drugs and see if there are contraindications

https://online.epocrates.com/noFrame/

[rockymoe]

Call your pharmacist, they know more than docs. My yongest daughter and her husband are Pharnacist. She keeps an eye on me. It amazes me that we can put all these drugs in our body and it doesn't hurt our livers!

[his3707]

my doc  took me off simvastatin  and changed me to the lowest dose of crestor 5 mg.   I  am sticking with crestor but doing 10 mg now that I am off off incivek

[flcyclist]

I just came across the following reference regarding simvastatin and the PI's.

Cholesterol-lowering medication is also contraindicated. “If you are unaware that a patient is on simvastatin and you give either boceprevir or telaprevir, the simvastatin level in the blood can go high and patients can develop muscle breakdown,” said Dr. Jensen.

http://www.idse.net//ViewArticle.aspx?ses=ogst&d=Hepatitis&d_id=213&i=ISSUE%3a+August+2011&i_id=753&a_id=18862