ombitasvir, paritaprevir, ritonavir, and dasabuvir

Action and Spectrum

Actions and Spectrum: 

ombitasvir, paritaprevir, ritonavir, and dasabuvir are antiviral drugs used to the treat chronic hepatitis C virus infections.  

• ombitasvir: ombitasvir is a direct-acting antiviral (DAA) drug in the class of NS5A inhibitors. It works by targeting the NS5A protein, which is important for the replication of the hepatitis C virus. By inhibiting this protein, ombitasvir blocks the virus’s ability to reproduce, helping to reduce the viral load in the body. 
• paritaprevir: paritaprevir is another direct-acting antiviral drug, a protease inhibitor. It inhibits the NS3/4A protease enzyme, which is important for the hepatitis C virus to replicate. By blocking this enzyme, paritaprevir helps to interrupt the virus’s life cycle and suppress its replication. 
• ritonavir: ritonavir is a pharmacokinetic enhancer or booster drug. It does not have direct antiviral activity against HCV but is included in the combination to enhance paritaprevir’s levels and duration of action. ritonavir achieves this by inhibiting certain liver enzymes responsible for metabolizing paritaprevir. As a result, paritaprevir remains in the bloodstream for a longer time, allowing for better treatment efficacy. 
• dasabuvir: dasabuvir is a non-nucleoside polymerase inhibitor. It targets the NS5B RNA-dependent RNA polymerase enzyme of the hepatitis C virus. By inhibiting this enzyme, dasabuvir interferes with the virus’s ability to replicate its genetic material, slowing down viral replication and reducing the viral load. 

Combining these four drugs into a single therapy creates a potent and effective treatment for chronic hepatitis C. The medications have different mechanisms of action, which complement each other and help prevent the development of drug resistance. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Abdominal/stomach pain 

Bloating of the abdomen or stomach 

Yellow eyes or skin 

Nausea and vomiting 

Red skin lesions 

Chills 

Itching 

Diarrhea 

Joint or muscle pain 

Sore throat 

Cough 

Light-colored stools 

Red, irritated eyes 

Blistering, peeling/loosening of the skin 

Dark urine 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity or Allergy: Individuals who have a known hypersensitivity or allergy to any of the components of ombitasvir, paritaprevir, ritonavir, or dasabuvir should not take this medication. 
• Severe Hepatic Impairment: Viekira Pak is not recommended in individuals with severe liver impairment (Child-Pugh Class C). The combination contains paritaprevir, and this drug’s metabolism may be affected in individuals with severe liver dysfunction. 
• Moderate Hepatic Impairment: Viekira Pak should be used cautiously in patients with moderate liver impairment (Child-Pugh Class B). The use of ritonavir, one of the components of the combination, may further affect liver function in these individuals. 
• Concomitant Use with Certain Medications: Viekira Pak may interact with other medications, leading to potentially harmful effects or decreased efficacy.  
• Pregnancy and Breastfeeding: The safety of Viekira Pak during pregnancy and breastfeeding has not been established. It is generally not recommended during pregnancy, and breastfeeding should be avoided while on this treatment. 
• Certain Medical Conditions: Viekira Pak may not be suitable for individuals with specific medical conditions, such as severe kidney impairment or heart conditions.  
• Pediatric Use: Safety and efficacy not established 

Caution 

• Drug Interactions: Viekira Pak can interact with other medications, including prescription, over-the-counter, and herbal products. These interactions may lead to reduced efficacy, increased side effects, or potential harm.  
• Liver Function: As Viekira Pak is primarily metabolized in the liver, it is essential to monitor liver function regularly, especially in individuals with pre-existing liver disease or impaired liver function. In some cases, dose adjustments may be necessary. 
• Renal Impairment: Although Viekira Pak is generally safe and well-tolerated in individuals with mild to moderate kidney impairment, caution should be exercised in individuals with severe renal dysfunction, as data on using this combination in such patients may be limited. 
• Risk of Hepatitis B Reactivation: Some individuals with current/prior hepatitis B virus (HBV) infection may experience reactivation of HBV while undergoing HCV treatment. Before starting Viekira Pak, patients should be tested for HBV infection. Those co-infected with HCV and HBV require close monitoring and appropriate management to prevent hepatitis B reactivation. 
• Risk of Symptomatic Bradycardia: ritonavir, one of the components of Viekira Pak, can prolong the QT interval and may cause bradycardia (slow heart rate) in susceptible individuals. Patients with a history of heart problems or those taking drugs that typically prolong the QT interval should be closely monitored during treatment. 
• Pregnancy and Breastfeeding: Viekira Pak during pregnancy is generally not recommended. Women of childbearing potential have to generally use effective contraception during treatment and for a specific period after completing therapy. Breastfeeding should be avoided while on this medication. 
• Resistance: Non-adherence to the prescribed dosing regimen or inadequate treatment duration can lead to developing drug-resistant HCV variants. It is crucial to take Viekira Pak precisely as prescribed and for the recommended treatment duration to maximize its effectiveness. 
• Pediatric Use: The safety and efficacy of Viekira Pak have not been established in children, so it is not typically prescribed for pediatric patients. 
• Allergic Reactions: Although uncommon, allergic reactions to any of the components of Viekira Pak may occur.

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Yes (ritonavir), Not known (dasabuvir, ombitasvir, paritaprevir),  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

ombitasvir, paritaprevir, ritonavir, and dasabuvir are direct-acting antiviral medications for chronic hepatitis C (HCV) infections. ombitasvir is an NS5A inhibitor that blocks viral replication by targeting the NS5A protein, while paritaprevir is a protease inhibitor that inhibits the NS3/4A protease enzyme essential for viral replication. ritonavir acts as a pharmacokinetic enhancer, increasing the plasma levels and duration of action of paritaprevir by inhibiting certain liver enzymes responsible for its metabolism.

dasabuvir is a non-nucleoside polymerase inhibitor that targets the NS5B RNA-dependent RNA polymerase enzyme, disrupting viral RNA synthesis. Together, this combination interferes with different stages of the HCV life cycle, resulting in reduced viral load and increased rates of sustained virologic response in patients with HCV genotype one infection. 

Pharmacodynamics: 

Mechanism of action: Each drug in the combination has a specific mechanism of action, and together, they target different stages of the HCV life cycle, leading to a more potent and effective treatment.  

• ombitasvir: ombitasvir is a direct-acting antiviral (DAA) drug in the class of NS5A inhibitors. It targets a specific protein called NS5A, essential for HCV replication and assembly. By inhibiting NS5A, ombitasvir interferes with forming new virus particles and halts the viral replication process. 
• paritaprevir: paritaprevir is another DAA drug and falls into the class of protease inhibitors. It specifically targets the NS3/4A protease enzyme of the hepatitis C virus. This enzyme is crucial for the virus to cleave viral polyproteins, a process necessary for viral replication. By inhibiting the NS3/4A protease, paritaprevir prevents the virus from producing functional proteins and disrupts its life cycle. 
• ritonavir: ritonavir is used in this combination as a pharmacokinetic enhancer or booster. It does not have direct antiviral activity against HCV. Instead, ritonavir inhibits certain liver enzymes called cytochrome P450 3A4 (CYP3A4). As a result, ritonavir increases plasma levels and extends the action of paritaprevir, which CYP3A4 also metabolizes. This enhancement allows for more sustained exposure to paritaprevir, improving its antiviral effectiveness. 
• dasabuvir: dasabuvir is a non-nucleoside polymerase inhibitor targeting the NS5B RNA-dependent RNA polymerase enzyme of the hepatitis C virus. This enzyme is essential for the replication of the viral RNA genome. By inhibiting the NS5B polymerase, dasabuvir interferes with the synthesis of new viral RNA, preventing the virus from replicating its genetic material and further spreading in the body. 

The combination of ombitasvir, ritonavir, paritaprevir, and dasabuvir is a potent antiviral treatment for chronic hepatitis C. The drugs work synergistically, targeting multiple stages of the HCV life cycle to inhibit viral replication and reduce the viral load.  

Pharmacokinetics: 

Absorption 

ombitasvir is taken orally, and it is well-absorbed from the gastrointestinal tract. 

paritaprevir is taken orally and is well-absorbed from the gastrointestinal tract. 

ritonavir is taken orally and is rapidly absorbed from the gastrointestinal tract. 

dasabuvir is taken orally and is well-absorbed from the gastrointestinal tract. 

Distribution 

ombitasvir has a high protein-binding capacity (greater than 99%), which limits its distribution in the bloodstream. 

Like ombitasvir, paritaprevir also has high protein-binding properties. 

ritonavir also has high protein-binding properties. 

dasabuvir has moderate protein-binding properties (over 99.5% of human plasma proteins). 

Metabolism 

ombitasvir is metabolized in the liver via cytochrome P450 (CYP) enzymes, mainly CYP3A4. 

paritaprevir is extensively metabolized in the liver via CYP3A4, and it is a substrate and inhibitor of this enzyme. 

ritonavir is extensively metabolized in the liver via CYP3A4. 

dasabuvir undergoes extensive metabolism in the liver, mainly via glucuronidation and oxidation. 

Elimination and Excretion 

The main route of elimination for ombitasvir is through the feces, primarily as metabolites. A smaller portion is excreted in the urine. The primary route of elimination for paritaprevir is through the feces, mainly as metabolites, while a smaller portion is excreted in the urine. 

Most ritonavir is metabolized, and the metabolites are eliminated in the feces and urine. The primary route of elimination for dasabuvir and its metabolites is through the feces, while a minor amount is excreted in the urine. 

Adminstartion

Administration: 

Oral administration 

ombitasvir, paritaprevir, ritonavir, and dasabuvir are usually available in a fixed-dose combination tablet. The specific brand name may vary depending on the country, but commonly, it is known as Viekira Pak or Viekira XR. It is generally used to treat chronic hepatitis C virus (HCV) infection. 

• Dosage: The recommended dosage might vary depending on the specific formulation and the patient’s characteristics, such as HCV genotype, liver function, and medical history. Always follow the prescribed dosage provided by your healthcare provider. 
• Administration: The combination tablet is typically taken orally, with or without food. Swallow the tablet whole; do not crush, break, or chew it. 
• Treatment Duration: The duration of treatment with Viekira Pak can vary based on factors like HCV genotype and whether the patient has received prior HCV treatment. Some patients may require a shorter treatment course, while others may need a longer one. The usual treatment duration can range from 12 to 24 weeks. 
• Co-administration with Ribavirin: Sometimes, Viekira Pak may be prescribed ribavirin, another antiviral medication, to enhance treatment efficacy.  
• Compliance: It is crucial to take the medication exactly as your healthcare provider prescribes. Missing doses or not completing the entire treatment course can lead to reduced effectiveness and the development of drug resistance. 
• Drug Interactions: As mentioned earlier, Viekira Pak can interact with other medications, including over-the-counter products and herbal supplements.  
• Regular Follow-up: During the treatment course, your healthcare provider will monitor your progress through regular check-ups and laboratory tests to assess treatment response and manage any side effects or complications. 
• Pregnancy and Breastfeeding: As mentioned earlier, Viekira Pak is not recommended during pregnancy, and breastfeeding should be avoided while on this medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ombitasvir, paritaprevir, ritonavir, and dasabuvir 

Pronounced: [ da-SA-bue-vir, om-BIT-as-vir, par-i-TA-pre-vir, rit-OH-na-vir ] 

Why do we use ombitasvir, paritaprevir, ritonavir, and dasabuvir? 

ombitasvir, paritaprevir, ritonavir, and dasabuvir are antiviral medications used to treat the chronic hepatitis C virus (HCV) infections in adults. This fixed-dose combination is known by the brand name Viekira Pak or Viekira XR.  

• Treatment of Chronic Hepatitis C: The primary use of ombitasvir, paritaprevir, ritonavir, and dasabuvir is for treating chronic hepatitis C infection. They are particularly effective against HCV genotypes 1a and 1b, common genotypes in many regions. The combination acts directly on the hepatitis C virus at different stages of its life cycle, inhibiting viral replication and reducing the viral load in the body. 
• Treatment-naive Patients: The combination is used in individuals with chronic hepatitis C who have not received any previous treatment for their HCV infection. It is an option for those newly diagnosed with hepatitis C and seeking treatment. 
• Treatment-Experienced Patients: Viekira Pak can also be prescribed for individuals who have previously received treatment for hepatitis C but did not achieve a sustained virologic response (SVR) or experienced viral relapse. These patients may be candidates for retreatment with this combination therapy. 
• Cirrhotic Patients: Combining ombitasvir, paritaprevir, ritonavir, and dasabuvir can treat chronic HCV infection in patients with compensated liver cirrhosis (liver scarring without liver failure). However, it may not be suitable for patients with severe liver impairment (Child-Pugh Class C). 
• HCV Genotype 1a with NS5A Resistance: Viekira Pak is approved for use in patients with HCV Genotype 1a who have specific mutations associated with NS5A resistance. The combination’s components, especially ombitasvir, are designed to target and overcome these resistant mutations. 
• Ribavirin Combination: Sometimes, Viekira Pak may be combined with another antiviral medication. Ribavirin may be considered for certain patients to enhance treatment efficacy, especially in difficult-to-treat patients or those with specific medical conditions.