Risk Of Developing Liver Cancer After HCV Treatment

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Sunday, October 2, 2011

How Do I Take Incivek-telaprevir ?


On November 4-12 the AASLD Annual Meeting will bring us new data on INCIVEK™
and VICTRELIS™.

Including updated information from a Phase 2 study evaluating the INCIVEK combination in people co-infected with HCV/HIV- genotype 1:all participants were not previously treated.

Bristol-Myers Squibb will be presenting the much anticipated data on their Interferon free combination -"Dual Oral Combination Therapy with the NS5A Inhibitor BMS-790052 and the NS3 Protease Inhibitor BMS-650032.


  • The first results of a Phase IIa study of the dual DAA regimen of BMS-790052 and the NS3 protease inhibitor BMS-650032 in HCV genotype 1b-infected patients who have not responded to prior alfa/RBV therapy (null responders), evaluating sustained virologic response 12 weeks post-treatment (SVR12)
You can view updates on the meeting here.

However, today its all about Incivek-telaprevir for the many people who may be starting therapy. Included in the information will be the dosing regimen for Incivek in combination with pegIFN/RBV, and a list of drugs that could cause drug interactions if used while taking Incivek. For instance in the medication guide, St. John's wort or products containing St. John’s wort can decrease the effectiveness of Incivek.

This information will include a comprehensive list of drugs that can lead to interactions with telaprevir, but lets start with a few drugs that you might be familiar with.

Antibiotics and Antidepressants

Antibiotics
Erythromycin which is used to treat certain infections caused by bacteria.
Telithromvcin-(Ketek®) used to treat certain types of pneumonia that is caused by bacteria.
Clarithromycin used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia, skin and skin structure infections. In addition, it is sometimes used to treat Legionellosis, Helicobacter pylori, and lyme disease.
Clarithromycin is available under several brand names, for example Crixan, Clarac, Biaxin, Klaricid, Klacid, Klaram, Klabax, Klacid, Claripen, Clarem, Claridar, Fromilid, Clacid, Clacee, Vikrol, Infex and Clariwin, Resclar.

A couple antidepressants also known as Benzodiazepine
Defined-The benzodiazepine family of depressants is used therapeutically to produce sedation, induce sleep, relieve anxiety and muscle spasms, and to prevent seizures.

Alprazolam-(Xanax®)
Midazolam- (Versed®)
Zolpidem - (Ambien®, Ambien CR®, Edluar™, Zolpimist®)

Take note that even grapefruit juice was mentioned. Please make sure that you discuss all your medications with your physician and pharmacist, do not rely solely on the list provided here today. Please take time to read the PDF provided by Vertex with the prescribing information.
*The PDF will explain all the drug interactions in detail.
The information compiled here is available @ CCO ,PDF-Prescribing information. and MedTV.

Telaprevir Dosing Guidelines for Hepatitis C

The recommended dosage for treating genotype 1 chronic hepatitis C is 750 mg-(Two 375mg tablets) three times a day. Telaprevir dose must not be reduced or interrupted. Doses should be given seven to nine hours apart. Telaprevir works best if it is taken at the same time each day.

Missing A Dose

If you miss a dose and remember the missed dose within 4 hours of the time you were scheduled to take it, take the missed dose with a snack or meal right away. However, if it is more than 4 hours since you were to take the dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. Call your doctor.

OVERDOSAGE
The highest documented dose administered is 1875 mg every 8 hours for 4 days in healthy subjects with INCIVEK alone. In that study, the following common adverse events were reported more frequently with the 1875 mg q8h regimen compared to the 750 mg q8h regimen: nausea, headache, diarrhea, decreased appetite, dysgeusia, and vomiting.

No specific antidote is available for overdose with INCIVEK. Treatment of overdose with INCIVEK consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. In the event of an overdose, it is reasonable to employ the standard supportive measures, such as, removing unabsorbed material from the gastrointestinal tract, employing clinical monitoring (including obtaining an electrocardiogram), and instituting supportive therapy if required.

Packaged

INCIVEKTM (telaprevir) is supplied as purple film-coated capsule-shaped tablets containing 375 mg of telaprevir. Each tablet is debossed with the characters “V 375” on one side and is packaged as follows:
28-day packer contains 4 weekly cartons of 7 blister strips each (6 tablets per blister strip)

Storage

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). After a bottle of telaprevir is first opened, the medication must be used within 28 days. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

The Rash
Serious Skin Reactions/Rash

Patients should be informed that INCIVEK combination treatment may cause rash. The rash can be severe and may be accompanied by fever and skin breakdown. Patients should promptly report any skin changes or itching to their healthcare provider. Patients should not stop INCIVEK due to rash unless instructed by their healthcare provider.

The rash is often mild and not serious in most cases. The advisory committee members were concerned about the three cases of Stevens Johnson Syndrome (SJS) which appeared during the telaprevir clinical trials. Keep in mind that there were approximately 2,200 trial participants. The serious skin reactions included a drug rash with eosinophilia and systemic symptoms known as (DRESS) and Stevens Johnson Syndrome (SJS). In the telaprevir trial the serious adverse reactions were reported in less then 1% , that is compared to none in the trial participants who received peginterferon alfa and ribavirin alone.

SCAR- Severe Cutaneous Adverse Reactions

Cutaneous drug reactions occur when your skin has a reaction to a drug.
DRESS is one of several terms that has been used to describe a severe idiosyncratic reaction to a drug that is characterized by a long latency of onset after exposure to the offending medication, a rash, involvement of internal organs, hematologic abnormalities and systemic illness.

Read more on the side effects during Telaprevir triple therapy- here" and all HCV therapy here.

If you haven't seen these yet, check out the two videos provided by Texas Medical Center discussing the side effects of standard therapy and a Patient video; Covering The New hepatitis C Drugs and Resistance .

Important Medication Information
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Take Telaprevir With Food

Telaprevir should be taken with a meal or snack that contains about 20 grams of fat. Do not take telaprevir without food. Examples of foods that contain about 20 grams of fat include:

  • A bagel with cream cheese

  • One half cup of nuts or trail mix

  • Three tablespoons of peanut butter

  • Two ounces of cheddar cheese.
First lets learn the lingo:

Defined; Response-Guided Therapy-Adjusting duration of therapy based on response.
Defined-Naive patients-never treated HCV before.
Defined-Relapsers: People whose viral load-(HCV RNA) drops to an undetectable level with treatment but rises again after treatment ends.
Defined- Partial response: At least a 2-log10 (100-times) drop in viral load-(HCV RNA), but inability to fully remove the virus from the blood by week 24.
Defined-Null responders: People who failed to reduce viral load-HCV RNA by at least a 2 log drop after 12 weeks of prior treatment, which is the currently recommended Food and Drug Administration (FDA) definition for clinical trials of investigational hepatitis C treatments.
Defined-Breakthrough :After dropping to undetectable levels, viral load-HCV RNA is detected again in blood during treatment.

What Is A 2 Log Drop?

Example: 2 log drop = 15,000,000 IU/Ml to 150,000 IU/mL; a viral load that starts at 15,000,000 IU/mL and does not decrease to 150,000 IU/mL or lower.

We begin with the treatment regimen for naive patients and relapsers, using response guided therapy. This includes people with compensated cirrhosis folks.

Treatment-naive patients and relapsers both RGT-response-guided therapy
*Response-Guided Therapy (RGT; Includes Compensated Cirrhotics)

Patients who have never treated before and relapsers with an undetectable viral load-HCV RNA at 4 and 12 weeks will be treated for a total of 24 weeks.
As Follows;
First 12 weeks with triple therapy- Telaprevir + pegIFN/RBV-
Additional 12 weeks with dual therapy - pegIFN/RBV alone
Total treatment time is 24 weeks

However:
For patients who have a detectable viral load lower then 1000 IU/mL at week 4 and12 total treatment time is @ 48 weeks
As Follows;
First 12 weeks with triple therapy- Telaprevir + pegIFN/RBV-
Additional dual therapy - pegIFN/RBV alone for 36 weeks
Total Treatment time 48 weeks.

*Treatment-naive patients with cirrhosis who have undetectable viral load-HCV RNA at Weeks 4 and 12 of telaprevir + pegIFN/RBV may benefit from an additional 36 weeks of pegIFN/RBV (48 wks total).

Next up Previous Partial or Null responders

As for previous partial or null responders treatment is as follows;
Treatment will begin with triple therapy-( Telaprevir + pegIFN/RBV) for 12 weeks
Dual therapy -pegIFN/RBV alone for an additional 36 weeks.
Total treatment time 48 weeks.

Now for the stopping rules-Or when your physician will discontinue therapy

If at week 4 and 12 your viral load-HCV RNA is more then 1000-IU/mL all treatment will be stopped.

If at week 24 you have a detectable viral load-HCV RNA pegIFN/RBV is discontinued.

At any time, for any reason pegIFN/RBV is stopped, then Telaprevir must be discontinued.

*In previously treatment-naive patients who responded well but still have detectable virus, some experts would continue pegIFN/RBV with HCV RNA monitoring.

Related Links;
Updated guidelines from the AASLD
DAAs promise great hope, but AASLD has expedited the writing and review of its practice guideline because those drugs do require a level of expertise for practitioners if optimum outcomes can be reached. In addition, treatment schedules will be complex and different for each DAA. The newly approved treatment schedules have more side effects than pegylated interferon and ribavirin, and should be managed carefully. The drugs are intended for use only in combination with pegylated interferon and ribavirin, and if not used in combination with those drugs, treatment will be ineffective and will cause emergence of antiviral-resistant mutants that could be difficult to treat subsequently.

Source; CCO pocket guide for using telaprevir or boceprevir.

Drug Interactions With Telaprevir

This list can be found @ MedTV

The following sections explain in detail the potentially negative reactions that can occur when telaprevir is combined with any of the drugs listed below.


Arrhythmia Medications

Telaprevir may increase blood levels of antiarrhythmic medications, potentially increasing your risk for serious side effects. Your healthcare provider will monitor you closely if you take these medications together.

Bosentan
Telaprevir can increase blood levels of bosentan, possibly increasing the risk for side effects. Your healthcare provider may choose to monitor you more closely if you take these medications together.

Calcium Channel Blockers
Telaprevir may increase blood levels of calcium channel blockers, possibly increasing your risk for side effects. Your healthcare provider may choose to monitor you more closely if you take these medicines together, and adjust your calcium blocker dosage if needed.

Certain Antibiotics
When telaprevir is taken with certain antibiotics, it can increase the blood levels of the antibiotics and telaprevir. Your healthcare provider will closely monitor you for potential side effects if you take these medications together.

Certain Antifungal Medications
Telaprevir may increase blood levels of certain antifungal medications, potentially increasing your risk for serious side effects. In addition, the antifungals listed above can increase blood levels of telaprevir. High ketoconazole and itraconazole doses should not be given to people who are taking telaprevir. Because of unpredictable effects on voriconazole blood levels, it should not be used at all in people taking telaprevir, unless absolutely necessary.

Certain Anti-Seizure Medications
Taking telaprevir with certain anti-seizure medications can affect the blood levels of telaprevir and of the seizure medicines. Telaprevir may increase blood levels of carbamazepine, and could increase or decrease blood levels of phenytoin and phenobarbital. In addition, any of those seizure medications may decrease telaprevir blood levels, potentially making it less effective. Talk to your healthcare provider before taking these medications together.

Certain Benzodiazepines
Telaprevir can increase blood levels of alprazolam and midazolam, potentially increasing your risk for side effects. It can also decrease blood levels of zolpidem.

Talk to your healthcare provider before taking telaprevir with one of these medicines. He or she may need to adjust the dose of your benzodiazepine or sedative. Oral midazolam and telaprevir should not be taken together. Injectable midazolam should only be given with telaprevir in a healthcare setting, where appropriate monitoring is possible.

Certain Immunosuppressants

Telaprevir can increase blood levels of cyclosporine, tacrolimus, and sirolimus, possibly increasing the risk for side effects. If you take these medications together, your healthcare provider will need to monitor you more closely for potential side effects. He or she will check your blood levels of your immunosuppressant, and decrease your dose as necessary.

Colchicine
Combining telaprevir with colchicine could increase the levels of colchicine in your body, increasing your risk for potentially serious side effects. People with kidney and liver disease (other than hepatitis C) should not take these medicines together. If they are taken together, a lower colchicine dose should be used.

Corticosteroids
Combining telaprevir with corticosteroids could result in increased levels of corticosteroids in the bloodstream, which could increase your risk for potentially serious side effects. INVICEK should not be used with oral, inhaled, or nasal corticosteroid medicines unless absolutely necessary.

CYP 3A4 Inhibitor Medications
The liver breaks down telaprevir using enzymes known as CYP 3A4 enzymes. Medications known as CYP 3A4 inhibitors can decrease the activity of these enzymes. Combining telaprevir with one of these CYP 3A4 inhibitors may increase the level of telaprevir in your bloodstream, increasing your risk for side effects. Talk to your healthcare provider before taking telaprevir with a CYP 3A4 inhibitor.

Digoxin
Telaprevir may increase levels of digoxin in the bloodstream. Your healthcare provider may decide to monitor your digoxin levels using a simple blood test, especially when you first start or stop taking telaprevir.

Desipramine
Taking telaprevir with desipramine could increase the level of desipramine in your bloodstream, potentially increasing your risk for side effects, such as nausea, dizziness, and low blood pressure. Your healthcare provider may need to give you a lower desipramine dose during telaprevir treatment.

Escitalopram
Telaprevir can decrease blood levels of escitalopram, potentially making it less effective. Although this is not considered a serious interaction, your healthcare provider may choose to monitor you more closely during telaprevir treatment and increase your escitalopram dose if needed.

Hormonal Birth Control
Telaprevir has been shown to decrease blood levels of ethinyl estradiol, which could make birth control pills that contain estrogen less effective. Women taking telaprevir should use two forms of birth control, other than hormonal birth control.


Methadone
Taking telaprevir with methadone could decrease levels of methadone in your bloodstream, potentially making it less effective. Your healthcare provider may choose to monitor your response to methadone, and adjust your dose if needed.

Non-Nucleoside Reverse Transcriptase Inhibitors
Combining telaprevir with efavirenz may result in lower blood levels of both efavirenz and telaprevir, possibly decreasing the effectiveness of the medications. Combining telaprevir with tenofovir may cause increased levels of tenofovir in the bloodstream, which could increase the risk for tenofovir side effects. Your healthcare provider will need to monitor you more closely if you take these medications together.

P-Glycoprotein (Pgp) Inhibitors
P-glycoprotein is a protein found in the body. One of its roles is to help remove substances, such as medications, out of the tissues so they can be excreted through the urine or feces. Pgp helps remove telaprevir from the body. Certain other medications (known as Pgp inhibitors) decrease the activity of Pgp.

Taking telaprevir with one of these Pgp inhibitors causes telaprevir to be removed more slowly, potentially increasing the amount of telaprevir in your bloodstream and increasing your risk for serious side effects. Your healthcare provider may choose to monitor you more closely for side effects if you take telaprevir with a Pgp inhibitor.

Phosphodiesterase Type-5 (PDE5) InhibitorsTaking telaprevir with a PDE5 inhibitor may increase the level of the PDE5 inhibitor in your bloodstream, potentially increasing your risk for side effects. Talk to your healthcare provider before taking these medications together.

Protease Inhibitors
Combining telaprevir with other protease inhibitors can decrease blood levels of telaprevir, while having varying effects on blood levels of the other protease inhibitors. For this reason, it is recommended that these medicines not be used together.

RifabutinRifabutin can decrease levels of telaprevir in your bloodstream, potentially making it less effective. Telaprevir may increase blood levels of rifabutin, potentially increasing your risk for side effects. It is recommended that these medicines not be used together.

Salmeterol
Telaprevir may increase blood levels of salmeterol, possibly increasing your risk for potentially serious side effects, including heart rhythm problems. You should not take salmeterol with telaprevir.

Trazodone
Taking telaprevir with trazodone could increase the level of trazodone in your bloodstream, potentially increasing your risk for side effects, such as nausea, dizziness, and low blood pressure. Your healthcare provider may need to give you a lower trazodone dose during telaprevir treatment.

Warfarin
Telaprevir can alter blood levels of warfarin. Your healthcare provider should monitor you more closely (by checking your INR) if you take warfarin with telaprevir.

Final Thoughts
I is possible that not all telaprevir drug interactions were discussed in this article. Therefore, you should talk with your pharmacist or healthcare provider about the specific interactions that may apply to you.

The List;

Telaprevir (INCIVEK™) may react with a number of other medications.
Some of the drugs that can lead to interactions with telaprevir include but are not limited to:
  • Arrhythmia medications, such as:
Amiodarone (Cordarone®, Pacerone®)

    • Flecainide (Tambocor™)

    • Lidocaine

    • Propafenone (Rythmol®, Rythmol® SR)

    • Quinidine



  • Certain antibiotics, such as:


  • Certain antifungal medications, such as:

    • Itraconazole (Sporanox®)

    • Ketoconazole (Nizoral®)

    • Posaconazole (Noxafil®)

    • Voriconazole (VFEND®)

  • Certain anti-seizure medications, such as:


  • Certain benzodiazepines and sedatives, such as:


  • Certain immunosuppresants, such as:



    • Betamethasone (Celestone®)

    • Cortisone

    • Dexamethasone (Decadron®)

    • Fludrocortisone (Florinef®)

    • Hydrocortisone (Cortef®)

    • Methylprednisolone (Depo-Medrol®, Medrol®)

    • Prednisolone (Ovapred®, Pediapred®)

    • Prednisone

    • Triamcinolone (Kenalog®, Aristospan®)
CYP 3A4 inducer medications, such as:


  • CYP 3A4 inhibitor medications, such as:



    • Delavirdine (Rescriptor®)

    • Efavirenz (Sustiva®)

    • Nevirapine (Viramune®)

    • Tenofovir (Viread®)

  • -glycoprotein inhibitors, such as:

    • Amiodarone (Cordarone®, Pacerone®)

    • Atorvastatin (Lipitor®, also found in Caduet®)

    • Carvedilol (Coreg®, Coreg CR®)

    • Clarithromycin (Biaxin®)

    • Cyclosporine (Gengraf®, Neoral®, Sandimmune®)

    • Darunavir (Prezista®)

    • Dipyridamole (Persantine®, also found in Aggrenox®)

    • Dronedarone (Multaq®)

    • Erythromycin

    • Grapefruit juice

    • Itraconazole (Sporanox®)

    • Ketoconazole (Nizoral®)

    • Lapatinib (Tykerb®)

    • Lopinavir and ritonavir (Kaletra®)

    • Mefloquine (Lariam®)

    • Nelfinavir (Viracept®)

    • Nicardipine (Cardene®)

    • Nilotinib (Tasigna®)

    • Progesterone

    • Propranolol (Inderal®, Inderal LA®, InnoPran XL®, also found in Inderide®)

    • Quinidine

    • Ranolazine (Ranexa®)

    • Reserpine

    • Ritonavir (Norvir®, also found in Kaletra®)

    • Saquinavir (Invirase®)

    • Sunitinib (Sutent®)

    • Tacrolimus (Prograf®, Protopic®)

    • Tamoxifen (Nolvadex®)

    • Verapamil (Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®)
    • Phosphodiesterase type-5 (PDE5) inhibitors, such as:

  • Protease inhibitors, such as:

    • Atazanavir (Reyataz®)

    • Darunavir (Prezista®)

    • Fosamprenavir (Lexiva®)

    • Lopinavir and ritonavir (Kaletra®)

    • Ritonavir (Norvir®)


In closing I would like to add that HCV advocate and their newsletters provide easy to understand clinical data and treatment information.
When I was diagnosed over a decade ago, these newsletters were my window into understanding HCV, may you find them as beneficial as I did.

Remember this, call the doc whenever you feel something isn't right, do not hesitate. You know your mind and body better then anyone.

Wishing you all a safe and successful journey.

Tina
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