Boceprevir

What is Boceprevir?

• Boceprevir (Victrelis) is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection.

Boceprevir

Boceprevir Structural Formula V.1

What are the uses of this medicine?

• Boceprevir (Victrelis) is used for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (≥18 years of age) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

• Boceprevir must not be used as a monotherapy.

Hepatitis C virus infection:

• The hepatitis C virus is a small RNA virus that is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in the United States as well as worldwide.
• Various approaches to antiviral therapy of chronic hepatitis C have been developed, starting in the 1980s with interferon alfa which was replaced in the 1990s by long acting forms of interferon (peginterferon) to which was added the oral nucleoside analogue, ribavirin.
• Between 2010 and 2015, several potent oral, direct acting anti-HCV agents were developed and combinations of these found to have marked activity against the virus, allowing for highly effective therapy without use of interferon with treatment courses of 12 to 24 weeks only.
• These direct acting agents included HCV protease (NS3/4) inhibitors, structural replication complex (NS5A) inhibitors and the HCV RNA polymerase (NS5B) inhibitors.
• The HCV protease inhibitors block the activity of the viral encoded protease that is essential in the posttranslational modification of the viral polypeptide, cleaving it into a series of structural and nonstructural (NS: enzyme) regions.
• The HCV proteases that have been developed are polypeptide-like molecules, modified amino acids that that resemble the specific amino acid sequence that the protease cleaves and act as competitive inhibitors of the protease enzyme.
• At least four HCV protease inhibitors (all having the suffix: -previrs) have been approved for use in the United States: boceprevir [2012], telaprevir [2012], simeprevir [2013], and paritaprevir [2014].

How does this medicine work?

• Boceprevir (boe se' pre vir) was one of the first direct acting agents developed as therapy of hepatitis C.
• Like other HCV protease inhibitors, boceprevir blocks the activity of the viral encoded protease (HCV nonstructural [NS] region 3/4) that is essential in the posttranslational modification of the viral polypeptide, that is cleaved into a series of structural and nonstructural (enzyme) regions.
• When used by itself, it results in rapid inhibition of HCV RNA levels, but resistance develops rapidly in a high proportion of patients.
• When combined with peginterferon and ribavirin, it was shown to provide a sustained inhibition of HCV RNA with a low rate of antiviral resistance.
• Triple therapy with boceprevir, peginterferon and ribavirin, when given for 44 to 48 weeks, increased the sustained virological response (SVR) rate from 40% to 50% (peginterferon and ribavirin alone) to 65% to 75% in patients with genotype 1.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• in pregnant women and in men whose female partners are pregnant
• with drugs that are highly dependent on CYP3A4/5 for clearance
• Potent CYP3A4/5 inducers

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Be sure to mention the following:

• alprazolam (Niravam, Xanax)
• anticoagulants ('blood thinners') such as warfarin (Coumadin)
• antifungal medications such as itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and voriconazole (Vfend)
• atorvastatin (Lipitor, in Caduet)
• bosentan (Tracleer)
• budesonide (Pulmicort, Rhinocort, Symbicort)
• buprenorphine (Buprenex, Butrans, Subutex, Suboxone)
• calcium channel blockers such as felodipine (Plendil), nicardipine (Cardene), and nifedipine (Adalat, Afeditab, Procardia)
• clarithromycin (Biaxin)
• colchicine (Colcrys, in Col-Probenecid)
• cyclosporine (Gengraf, Neoral, Sandimmune)
• desipramine (Norpramin)
• dexamethasone
• certain medications for erectile dysfunction such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra, Staxyn)
• certain medications for HIV such as atazanavir taken with ritonavir, darunavir taken with ritonavir, efavirenz (Sustiva, in Atripla), lopinavir taken with ritonavir, and ritonavir (Norvir, in Kaletra)
• certain medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone), digoxin (Lanoxin), flecainide (Tambocor), propafenone (Rythmol), and quinidine
• methadone (Dolophine, Methadose)
• midazolam given intravenously (into a vein)
• rifabutin (Mycobutin)
• salmeterol (Serevent, in Advair)
• sirolimus (Rapamune)
• tacrolimus (Prograf)
• trazodone
• alfuzosin (Uroxatral)
• ergot medications such as dihydroergotamine (D.H.E. 45, Migranal), ergonovine, ergotamine (Ergomar, in Cafergot, in Migergot) or methylergonovine
• cisapride (Propulsid) (not available in the U.S.)
• drospirenone (in some oral contraceptives such as Beyaz, Gianvi, Ocella, Safyral, Yasmin, Yaz, and Zarah)
• lovastatin (Altoprev, Mevacor)
• certain medications for seizures such as carbamazepine (Carbatrol, Equetro, Tegretol), phenobarbital, or phenytoin (Dilantin)
• midazolam taken by mouth
• pimozide (Orap)
• rifampin (Rifadin, Rimactane, in IsonaRif, in Rifamate, in Rifater)
• sildenafil (only Revatio brand used for lung disease)
• simvastatin (Simcor, in Vytorin)
• tadalafil (only Adcirca brand used for lung disease)
• St. John's wort
• triazolam (Halcion)

Is this medicine FDA approved?

• It was approved by the FDA in May 2011.
• In January 2015, Merck announced that they would be voluntarily withdrawing Victrelis from the market due to the overwhelming superiority of newer direct-acting antiviral agents, such as ledipasvir/sofosbuvir.

How should this medicine be used?

Recommended dosage:

• 800 mg administered orally three times daily (every 7 - 9 hours) with food (a meal or light snack).
• Victrelis must be administered in combination with peginterferon alfa and ribavirin.

Administration:

• Boceprevir comes as a capsule to take by mouth.
• It is usually taken with a meal or light snack three times a day (every 7 to 9 hours).
• Take boceprevir at around the same times every day.
• You will take peginterferon alfa and ribavirin for 4 weeks before you begin treatment with boceprevir.
• Then you will take all three medications for 12 to 44 weeks.
• After this time, you will stop taking boceprevir, but you may continue to take peginterferon alfa and ribavirin for an additional number of weeks.
• The length of your treatment depends on your condition, how well you respond to the medication, and whether you experience severe side effects.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 200 mg

This medicine is available in fallowing brand namesː

• Victrelis

What side effects can this medication cause?

The most common side effects of this medicine include:

• fatigue
• anemia
• nausea
• headache
• dysgeusia
• rash
• neutropenia

Victrelis may cause some serious side effects which may include:

• shortness of breath
• dizziness
• fainting
• weakness
• sore throat, fever, chills, and other signs of infection

What special precautions should I follow?

• Use of Victrelis with Ribavirin and Peginterferon alfa may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; use two or more forms of contraception, and have monthly pregnancy tests.
• Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of Victrelis to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. If hemoglobin is less than 10 g/dL, a decrease in dosage or interruption of ribavirin is recommended; and if hemoglobin is less than
• 8.5 g/dL, discontinuation of ribavirin is recommended.
• The addition of Victrelis to peginterferon alfa and ribavirin may result in worsening of neutropenia associated with peginterferon alfa and ribavirin therapy alone. Decreases in neutrophil counts may require dose reduction or discontinuation of peginterferon alfa and ribavirin.
• Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to initiating Victrelis combination therapy. Complete blood counts should be obtained at Treatment
• Weeks 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate.
• It is not known whether Victrelis is excreted into human breast milk. Because of the potential for adverse reactions from the drug in nursing infants, a decision must be made whether to discontinue nursing or discontinue treatment with
• Victrelis, taking into account the importance of the therapy to the mother.
• Boceprevir has not been linked to instances of acute liver injury during therapy but, when combined with peginterferon and ribavirin, has been associated with cases of hepatic decompensation in patients with preexisting cirrhosis.
• Patients should be advised that Victrelis must not be used alone due to the high probability of resistance without combination anti-HCV therapies.
• If a patient misses a dose and it is less than 2 hours before the next dose is due, the missed dose should be skipped. If a patient misses a dose and it is 2 or more hours before the next dose is due, the
• patient should take the missed dose with food and resume the normal dosing schedule.
• Patients should be informed that the effect of treatment of hepatitis C infection on transmission is not known, and that appropriate precautions to prevent transmission of the hepatitis C virus should be taken.

What to do in case of emergency/overdose?

Management of overdosage:

• There is no specific antidote for overdose with Victrelis.
• Treatment of overdosage with Victrelis should consist of general supportive measures, including monitoring of vital signs, and observation of the
• patient’s clinical status.

Can this medicine be used in pregnancy?

• Pregnancy Category X.
• Victrelis must be administered in combination with peginterferon alfa and ribavirin.
• Ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant.

Can this medicine be used in children?

• The safety, efficacy, and pharmacokinetic profile of Victrelis in pediatric patients have not been studied.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• boceprevir

Inactive ingredients:

• sodium lauryl sulfate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, pre-gelatinized starch, and magnesium stearate. The red capsule cap consists of gelatin, titanium dioxide, D&C Yellow #10, FD&C
• Blue #1, and FD&C Red #40. The yellow capsule body contains gelatin, titanium dioxide, D&C Yellow #10, FD&C Red #40, and FD&C Yellow #6. The capsule is printed with red and yellow ink. The red ink
• contains shellac and red iron oxide, while the yellow ink consists of shellac, titanium dioxide, povidone and D&C Yellow #10 Aluminum Lake.

Who manufactures and distributes this medicine?

• Schering Corporation, a subsidiary of MERCK & CO., INC., Whitehouse Station, NJ, USA

What should I know about storage and disposal of this medication?

• Victrelis Capsules should be refrigerated at 2-8°C (36-46°F) until dispensed.
• Avoid exposure to excessive heat.
• For patient use, refrigerated capsules of Victrelis can remain stable until the expiration date printed on the label. Victrelis can also be stored at room temperature up to 25°C (77°F) for 3 months.
• Keep container tightly closed.

The following are drugs for Hepatitis C:

Interferon Based Therapies

• Alpha Interferon and Peginterferon, Ribavirin

HCV NS5A Inhibitors

• Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir

HCV NS5B (Polymerase) Inhibitors

• Dasabuvir, Sofosbuvir

HCV Protease Inhibitors

• Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir

Combination Therapies

• Epclusa, Harvoni, Mavyret, Technive, Viekira Pak, Vosevi, Zepatier

• Dailymed label info on Boceprevir
• FDA Boceprevir

Boceprevir Resources
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