Ombitasvir/paritaprevir/ritonavir

Dosage Forms & Strengths

ombitasvir/paritaprevir/ritonavir

tablet

• 12.5mg/75mg/50mg

Chronic Hepatitis C

Indicated in combination with ribavirin for genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis

2 tablets PO qAM for 12 wk with a meal, without regard to fat or calorie content

Recommended to be used in combination with ribavirin, although may be considered for treatment-naïve patients without cirrhosis who cannot take or tolerate ribavirin

Dosage Modifications

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment required
• Moderate or severe (Child-Pugh B, Child-Push C): Contraindicated

Renal impairment

• CrCl >15 mL/min: No dosage adjustment necessary
• DEnd-stage renal disease: Not studied
• For patients that require ribavirin, refer to the ribavirin prescribing information for information regarding use with renal impairment

Dosing Considerations

Prior to initiation, assess hepatic laboratory and clinical evidence of hepatic decompensation

Prior to initiation of ribavirin, assess for underlying cardiac disease

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

<18 years: Safety and efficacy not established

Chronic Hepatitis C (Orphan)

Orphan designation for treatment of pediatric patients with chronic HCV infection

Sponsor

• AbbVie Inc; 1 North Waukegan Road; North Chicago, Illinois 60064

Mechanism of Action

Ombitasvir: Inhibits HCV NS5A protein, which is required for viral replication

Paritaprevir: NS3/4A serine protease inhibitor; NS3/4A protease is needed for proteolytic cleavage of the HCV encoded polyprotein into mature forms

Ritonavir: Protease inhibitor that is used as a "boosting agent" to increase paritaprevir serum levels

Absorption

Peak plasma time: 4-5 hr

Steady-state achieved: ~12 days

Absolute bioavailability (when administered with ritonavir): 48.1% (ombitasvir); 52.6% (paritaprevir)

AUC

• Ombitasvir: 1239 ng•hr/mL
• Paritaprevir: 2276 ng•hr/mL
• Ritonavir: 6072 ng•hr/mL

Peak plasma concentration

• Ombitasvir: 62 ng/mL
• Paritaprevir: 194 ng/mL
• Ritonavir: 543 ng/mL

Distribution

Protein bound

• Ombitasvir: 99.9%
• Paritaprevir: 98.6%
• Ritonavir: >99%

Vd

• Ombitasvir: 173 L
• Paritaprevir: 103 L
• Ritonavir: 21.5 L

Metabolism

Ombitasvir: Predominantly metabolized by amide hydrolysis followed by oxidative metabolism

Paritaprevir: Predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5

Ritonavir: Predominantly metabolized by CYP3A, and to a lesser extent, by CYP2D6

Elimination

Half-life

• Ombitasvir: 21-25 hr
• Paritaprevir: 5.5 hr
• Ritonavir: 4 hr

Excretion

• Ombitasvir: 90.2% feces; 1.91% urine
• Paritaprevir: 88% feces; 8.8% urine
• Ritonavir: 86.4% feces; 11.3% urine

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• liver problems--upper stomach pain or swelling, confusion, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• nausea;
• sleep problems (insomnia); or
• feeling weak or tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ombitasvir/paritaprevir/ritonavir is a prescription medication used to treat genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. It is given in combination with ribavirin for 12 weeks. 

It is a single product containing 3 ingredients: ombitasvir, paritaprevir and ritonavir.

Ombitasvir belongs to a group of drugs called NS5A inhibitors. Paritaprevir belongs to a group of drugs called NS3/4A protease inhibitor. Ritonavir is in a class of medications called protease inhibitors. Together these help to stop the virus that causes hepatitis C from spreading inside the body.

This medication comes in tablet form and is taken once a day, with a meal without regard to fat or calorie content. 

Common side effects of ombitasvir/paritaprevir/ritonavir include feeling weak, tiredness, nausea, and sleep problems. Do not drive or operate heavy machinery until you know how this medication affects you. 

Ombitasvir & Paritaprevir & Ritonavir may be found in some form under the following brand names:

• Technivie

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• alfuzosin hydrochloride (Uroxatral)
• carbamazepine (Carbatrol, Epitol, Equetro, Tegretol)
• efavirenz (Atripla, Sustiva)
• ergot containing medicines including: ergotamine tartrate (Cafergot, Ergomar, Ergostat, Medihaler, Migergot, Wigraine, Wigrettes), dihydroergotamine mesylate (D.H.E. 45, Migranal), and methylergonovine (Ergotrate, Methergine)
• ethinyl estradiol-containing medicines: combination birth control pills or patches (such as Lo Loestrin FE, Norinyl, Ortho TriCyclen Lo, and Ortho Evra), hormonal vaginal rings (such as NuvaRing), and the hormone replacement therapy medicine, Fem HRT 
• cholesterol lowering medications such as lovastatin (Advicor, Altoprev, Mevacor) and simvastatin (Simcor, Vytorin, Zocor)
• midazolam, when taken by mouth
• triazolam (Halcion) when taken by mouth
• phenytoin, (Dilantin, Phenytek)
• phenobarbital (Luminal)
• pimozide (Orap)
• rifampin (Rifadin, Rifamate, Rifater, Rimactane)
• sildenafil citrate (Revatio), when taken for pulmonary artery hypertension (PAH)
• St. John’s wort (Hypericum perforatum) or a product that contains St. John’s wort

This is not a complete list of ombitasvir/paritaprevir/ritonavir drug interactions. Ask your doctor or pharmacist for more information. 

Serious side effects have been reported with ombitasvir/paritaprevir/ritonavir including the following:

• can cause increases in your liver function blood test results, especially if you use ethinyl estradiol-containing medicines (such as some birth control products).
  • You must stop using ethinyl estradiol-containing medicines before you start treatment with this medication.
  • If you use these medicines as a method of birth control, you must use another method of birth control during treatment with ombitasvir/paritaprevir/ritonavir, and for about 2 weeks after you finish treatment with this medication. Your healthcare provider will tell you when you may begin taking ethinyl estradiol containing medicines.
  • Your healthcare provider should do blood tests to check your liver function during the first 4 weeks and then as needed, during treatment with ombitasvir/paritaprevir/ritonavir.
• Serious liver injury. This may occur mostly in patients with underlying advanced liver disease. Your healthcare provider may tell you to stop taking this medication if you develop signs or symptoms of liver problems. Tell your healthcare provider right away if you develop any of the following symptoms, or if they worsen during treatment with this medication:
  • tiredness
  • weakness
  • loss of appetite
  • nausea and vomiting
  • yellowing of your skin or eyes
  • color changes in your stools
• Multiple Drug Interactions. Ombitasvir/paritaprevir/ritonavir can interact with many medications.
  • Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
  • Keep a list of your medicines to show your healthcare provider and pharmacist. 
  • Ask your healthcare provider or pharmacist for a list of medicines that interact with ombitasvir/paritaprevir/ritonavir.
  • Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take this medication with other medicines.
  • When you finish treatment with ombitasvir/paritaprevir/ritonavir:
    • If your doctor changed the dose of one of your usual medicines during treatment with ombitasvir/paritaprevir/ritonavir: Ask your healthcare provider about when you should change back to your original dose after you finish treatment with ombitasvir/paritaprevir/ritonavir.
    • If your doctor told you to stop taking one of your usual medicines during treatment with ombitasvir/paritaprevir/ritonavir: Ask your healthcare provider if you should start taking these medicines again after you finished treatment with ombitasvir/paritaprevir/ritonavir.

Do not take ombitasvir/paritaprevir/ritonavir if you:

• are allergic to ombitasvir/paritaprevir/ritonavir or any of its ingredients
• have had a severe skin rash after taking ritonavir (Norvir)
• have severe liver problems
• you take any of the medications listed in Drug Interactions. 

Your doctor will want to monitor your liver function closely and may discontinue this medication if your liver function worsens.  

Before taking ombitasvir/paritaprevir/ritonavir, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to ombitasvir/paritaprevir/ritonavir or any of its ingredients
• have had a severe skin rash after taking ritonavir (Norvir)
• if you have a history of hepatitis B infection
• have liver problems other than hepatitis C infection
• have had a liver transplant. If you take the medicines tacrolimus (Prograf) or cyclosporine (Gengraf, Neoral, Sandimmune) to help prevent rejection of your transplanted liver, the amount of these medicines in your blood may increase during treatment with ombitasvir/paritaprevir/ritonavir.
  • Your healthcare provider should check the level of tacrolimus or cyclosporine in your blood, and if needed may change your dose of these medicines or how often you take them. When you finish taking ombitasvir/paritaprevir/ritonavir or if you have to stop ombitasvir/paritaprevir/ritonavir for any reason, your healthcare provider should tell you what dose of tacrolimus or cyclosporine to take and how often you should take it.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed
• you take any of the listed medications in Drug Interactions Section

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

There is a risk of hepatitis B virus (HBV) becoming an active infection in those who have a current or previous infection with HBV and is treated with a certain antiviral medication (a direct-acting antiviral) to treat hepatitis C virus. Your healthcare provider will screen and monitor for HBV in those taking a direct-acting antiviral. Tell your healthcare provider if you have a history of hepatitis B infection or other liver problems before you are treated for hepatitis C.