Technivie

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Ombitasvir, paritaprevir, and ritonavir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• rash
• reddening of the skin
• hives
• itching
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• weakness
• confusion

Ombitasvir, paritaprevir, and ritonavir may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Ombitasvir, paritaprevir, and ritonavir are antiviral medicines that prevent hepatitis C virus (HCV) from multiplying in your body.

Ombitasvir, paritaprevir, and ritonavir (Technivie) is a combination medicine used to treat genotype 4 chronic hepatitis C in adults without cirrhosis. This medicine is sometimes given together with another drug called ribavirin.

Ombitasvir, paritaprevir, and ritonavir may also be used for purposes not listed in this medication guide.

Do not use this medicine together with ribavirin if you are pregnant, or if you are a man and your sexual partner is pregnant.

Before you start taking Technivie, you must stop using certain birth control pills or hormone replacement medicines. Ask your doctor about using non-hormonal birth control to prevent pregnancy.

You should not use Technivie if you are allergic to ombitasvir, paritaprevir, or ritonavir, or if you have:

• moderate to severe liver disease (including cirrhosis); or
• if you have ever had a severe skin rash after taking ritonavir (Norvir).

If you take Technivie with ribavirin: There may be other reasons you should not take this combination treatment. Tell your doctor about all your medical conditions.

Some medicines can interact with Technivie and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

• alfuzosin;
• colchicine;
• efavirenz;
• pimozide;
• rifampin;
• sildenafil (Revatio), when taken for pulmonary artery hypertension (PAH);
• St. John's wort;
• oral midazolam (Versed), or triazolam;
• birth control pills or patches--Lo Loestrin FE, Norinyl, Ortho Tri-Cyclen Lo, Ortho Evra, and others;
• hormone replacement therapy such as Fem HRT;
• a vaginal ring such as NuvaRing;
• cholesterol-lowering medicine--gemfibrozil, lovastatin, simvastatin (Zocor, Vytorin, Simcor);
• ergot medicine--dihydroergotamine, ergotamine, ergonovine, methylergonovine; or
• seizure medicine--carbamazepine, phenytoin, phenobarbital.

Before you start taking Technivie, you must stop using medicine that contains ethinyl estradiol. This includes certain birth control pills or hormone replacement medicines. Ask your doctor about using non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy while taking Technivie and for 2 weeks after your treatment ends.

To make sure Technivie is safe for you, tell your doctor if you have:

• liver problems other than hepatitis C;
• HIV (human immunodeficiency virus); or
• if you have received a liver transplant.

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

However, if you also take ribavirin, you may need to have a negative pregnancy test before your treatment starts. Ribavirin is known to cause birth defects or death in an unborn baby.

While you are taking Technivie with ribavirin: Use birth control to prevent pregnancy whether you are a man or a woman. Ribavirin use by either parent may cause birth defects. Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking ribavirin.

It is not known whether Technivie passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Technivie is not approved for use by anyone younger than 18 years old.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Technivie falls into category B. There are no well-done studies that have been done in humans with Technivie. In animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication. It is not known if Technivie will harm your unborn baby. Technivie should not be given to pregnant women or in men whose female partners are pregnant. 

If you take too much Technivie call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

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. 

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;

• headache, mood changes;

• muscle or joint pain;

• dizziness, feeling weak or tired;

• sleep problems (insomnia); or

• itching.

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.

Paritaprevir and ritonavir metabolized principally by CYP3A.1 Ritonavir inhibits CYP3A4.1

Paritaprevir and ritonavir inhibit P-glycoprotein (P-gp) transport;1 ombitasvir, paritaprevir, and ritonavir are substrates of P-gp.1

Paritaprevir and ritonavir inhibit breast cancer resistance protein (BCRP);1 paritaprevir is a substrate of BCRP.1

Paritaprevir is a substrate and inhibitor of organic anion transporting polypeptide (OATP) 1B1 and 1B3.1

Ombitasvir, paritaprevir, and ritonavir do not inhibit organic anion transporter (OAT) 1 and not expected to inhibit OAT3, organic cation transporter (OCT) 2, or multidrug and toxin extrusion protein (MATE) 1 or MATE2K at clinically important concentrations.1 Ombitasvir, paritaprevir, and ritonavir are neither inhibitors or substrates of OCT1.1

The following interactions are based on studies using ombitasvir/paritaprevir/ritonavir or studies using ombitasvir/paritaprevir/ritonavir given with dasabuvir.1 When ombitasvir/paritaprevir/ritonavir used, consider interactions associated with each drug in the fixed combination.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potent CYP3A inhibitors: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir (increased paritaprevir and ritonavir concentrations).1

CYP3A4 substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir (increased concentrations of CYP3A4 substrate).1

Drugs Affecting or Affected by P-glycoprotein Transport

P-gp substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir (increased concentrations of P-gp substrate).1

P-gp inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir).1

Drugs Affecting or Affected by Breast Cancer Resistance Protein

BCRP substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir (increased concentrations of BCRP substrate).1

BCRP inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir).1

Drugs Affecting or Affected by Organic Anion Transport Polypeptides

OATP1B1 or OATP1B3 substrates: Possible pharmacokinetic interactions with ombitasvir/paritaprevir/ritonavir (increased concentrations of OATP1B1 or OATP1B3 substrate).1

OATP1B1 or OATP1B3 inhibitors: Possible pharmacokinetic interactions (increased concentrations of various components of ombitasvir/paritaprevir/ritonavir).1

Specific Drugs

• Ombitasvir/paritaprevir/ritonavir provides fixed combination containing 2 direct-acting antivirals (DAAs) with activity against HCV.1

• Ombitasvir and paritaprevir have different mechanisms of action against HCV and non-overlapping resistance profiles.1 No in vitro evidence of antagonistic anti-HCV effects between ombitasvir and paritaprevir in HCV replicon studies.180

• Ritonavir, a potent CYP3A inhibitor, is included in the fixed combination to increase paritaprevir plasma concentrations and AUC;1 does not have activity against HCV.1

• Ombitasvir is an HCV NS5A replication complex inhibitor (NS5A inhibitor).1 9 10 11 Exact role of NS5A has not been fully elucidated,9 10 11 but is essential for viral replication and virion assembly.1 9 10 11 In vitro studies using cell-based replicon assays indicate that ombitasvir is active against HCV genotype 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a.1 9 10 11 Certain amino acid substitutions in NS5A of HCV genotype 4a (e.g., L28V) and genotype 4d (e.g., L28V, T58S) selected in cell culture and associated with reduced in vitro susceptibility to ombitasvir.1 3

• Paritaprevir is an HCV NS3/4A protease inhibitor.1 Inhibits HCV NS3/4A protease, thereby blocking enzyme activity and formation of proteins essential for viral replication (i.e., NS3, NS4A, NS4B, NS5A, NS5B).1 Based on biochemical assays, paritaprevir active against HCV genotypes 4a;1 in vitro studies using cell-based replicon assays indicate that paritaprevir is active against genotypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, and 6a.1 Certain amino acid substitutions in NS3 of HCV genotype 4a (e.g., R155C, A156T/V, D168H/V) and genotype 4d (e.g., Y56H, D168V) have been selected in cell culture and have been associated with reduced in vitro susceptibility.1 In HCV genotype 4d replicons, combination of Y56H and D168V substitutions reduced paritaprevir activity relative to single Y56H or D168V substitutions.1 3

• Cross-resistance expected within each HCV antiviral class (e.g., NS5A inhibitors, NS3/4A protease inhibitors).1

• Impact of prior treatment with ombitasvir or paritaprevir on efficacy of other NS5A inhibitors or NS3/4A protease inhibitors not evaluated.1 Efficacy of ombitasvir/paritaprevir/ritonavir not evaluated in patients in whom previous treatment with a regimen that contained an NS5A inhibitor, NS3/4A protease inhibitor, or NS5B polymerase inhibitor failed.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Feeling very tired or weak.
• Very bad and sometimes deadly liver problems have happened with this medicine. Some people have needed a liver transplant. These problems most often happened within 1 to 4 weeks of starting treatment. Most people who have had them already had liver problems before starting Technivie. Tell your doctor right away if you have signs of liver problems like dark urine, feeling tired or weak, change in thinking clearly and with logic, not hungry, upset stomach or stomach pain, stomach swelling, light-colored stools, throwing up, or yellow skin or eyes.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Technivie is indicated in combination with ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis [see Clinical Studies (14)].

Before you start treatment with Technivie, your doctor may perform tests to make sure you do not have conditions that would prevent you from safely using this medicine.

Technivie is usually taken for 12 weeks. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

The monthly Technivie carton contains enough tablets for you to take this medicine for 4 weeks (28 days in a row). Each of the 4 weekly cartons contains 7 daily dose packs.

Take 2 tablets at the same time every morning with food.

You will need frequent blood tests to check your liver function.

Hepatitis C is often treated with a combination of drugs. Use all medications as directed by your doctor. Read all patient information, medication guides, and instruction sheets provided to you. Do not change your doses or medication schedule without your doctor's advice. Every person with chronic hepatitis C should remain under the care of a doctor.

You should not stop using this medicine suddenly. Stopping suddenly could make your condition harder to treat with hepatitis C antiviral medicine.

If you have ever had hepatitis B, Technivie can cause this condition to come back or get worse. You will need liver function tests during treatment and for several months after you stop using this medicine.

Store the Technivie at room temperature away from moisture and heat. Do not remove the tablets from a daily dose package until you are ready to take the medicine.

Usual Adult Dose for Chronic Hepatitis C:

2 tablets orally once a day (in the morning)

Recommended Regimen and Duration of Therapy:
-Genotype 4, without cirrhosis: Ombitasvir/paritaprevir/ritonavir and ribavirin for 12 weeks

Comments:
-Before starting this drug, baseline hepatic laboratory and clinical parameters should be assessed.
-The manufacturer product information should be consulted for ribavirin dosing recommendations, including dose adjustments.
-Use of this drug without ribavirin may be considered for therapy-naive patients who cannot take or tolerate ribavirin.

Use: In combination with ribavirin, for the treatment of patients with genotype 4 chronic HCV infection without cirrhosis

Taking Technivie will not prevent you from passing hepatitis C to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HCV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Get emergency medical help if you have signs of an allergic reaction to Technivie: 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 Technivie side effects may include:

• nausea;

• headache, mood changes;

• muscle or joint pain;

• dizziness, feeling weak or tired;

• sleep problems (insomnia); or

• itching.

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.

When you start or stop taking Technivie, your doctor may need to adjust the doses of any other medicines you take on a regular basis.

Many drugs can interact with ombitasvir, paritaprevir or ritonavir. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Technivie, especially:

• metformin;

• quetiapine;

• heart or blood pressure medicine;

• medicine to treat HIV or AIDS;

• narcotic pain medicine;

• antifungal medicine - ketoconazole, voriconazole;

• asthma or allergy medicine - including Flonase, Veramyst, Flovent, Advair, Arnuity Ellipta, Serevent Diskus, and others; or

• medicine to prevent organ transplant rejection - cyclosporine, tacrolimus.

Many drugs can interact with ombitasvir, paritaprevir or ritonavir, and some drugs should not be used together. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Technivie. Give a list of all your medicines to any healthcare provider who treats you.