Health Canada has reviewed the potential risk of severe cutaneous adverse reactions (SCAR) with the use of sofosbuvir-containing products and concluded that there may be a link between the use of sofosbuvir-containing products and the risk of Stevens Johnson syndrome (SJS), but did not confirm a link with the risk of other types of SCAR (eg, erythema multiforme, toxic epidermal necrolysis). Health Canada will work with manufacturers to update the Canadian product safety information for sofosbuvir-containing products to include the risk of SJS.
Further information may be found at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00256.
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with sofosbuvir. HBV reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Note: Prior to initiating therapy, test patient for evidence of hepatitis B infection (current or prior).
Chronic hepatitis C infection (monoinfection or coinfected with HIV-1); treatment-naive or treatment-experienced without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Note: Use in combination with ribavirin. Treatment-experienced refers to patients who have failed prior treatment with an interferon-based regimen with or without ribavirin. Sofosbuvir dosage reduction is not recommended; however, other hepatitis C treatments (eg, ribavirin) may require dosage adjustments for toxicity. If other hepatitis C treatments require discontinuation due to toxicity, then discontinue sofosbuvir as well.
Children ≥3 years and Adolescents:
Patient weight:
<17 kg: Pellets: Oral: 150 mg once daily.
17 to <35 kg: Pellets, tablets: Oral: 200 mg once daily.
≥35 kg: Pellets, tablets: Oral: 400 mg once daily.
Treatment duration based on genotype:
Genotype 2: 12 weeks.
Genotype 3: 24 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥3 years and Adolescents:
eGFR ≥30 mL/minute: No dosage adjustment necessary.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling. Predominant metabolite accumulates (up to 20-fold) in impaired renal function.
End stage renal disease, including hemodialysis patients: There are no dosage adjustments provided in the manufacturer's labeling. Predominant metabolite accumulates (up to 20-fold) in impaired renal function.
Dialysis: During a 4-hour dialysis session, 18% of sofosbuvir dose was removed.
Children ≥3 years and Adolescents: Mild, moderate, or severe impairment: No dosage adjustment necessary.
(For additional information see "Sofosbuvir: Drug information")
Chronic hepatitis C (CHC):
Genotype 3, peginterferon + ribavirin treatment–experienced patients with compensated cirrhosis (Child-Pugh class A) (alternative agent): Oral: 400 mg once daily with concomitant elbasvir/grazoprevir for 12 weeks (Ref).
All genotypes, patients with prior glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir treatment failure, without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Oral: 400 mg once daily in combination with ribavirin and glecaprevir/pibrentasvir for 16 weeks (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Estimated glomerular filtration rate (eGFR) ≥30 mL/minute: No dosage adjustment necessary.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Predominant metabolite accumulates in impaired renal function.
End stage renal disease (ESRD), including hemodialysis patients: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Predominant metabolite accumulates in impaired renal function.
Mild, moderate, or severe impairment (Child-Pugh class A, B, or C): No dosage adjustment necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with combination therapy.
>10%:
Dermatologic: Pruritus (11% to 27%), skin rash (8% to 18%)
Gastrointestinal: Decreased appetite (18%), diarrhea (9% to 12%), nausea (22% to 34%)
Hematologic & oncologic: Anemia (6% to 21%), neutropenia (<1% [interferon-free regimen] to 17% [interferon-containing regimen])
Nervous system: Chills (2% to 17%), fatigue (30% to 59%), headache (24% to 36%), insomnia (15% to 25%), irritability (10% to 13%)
Neuromuscular & skeletal: Asthenia (5% to 21%), myalgia (6% to 14%)
Respiratory: Flu-like symptoms (6% to 16%)
Miscellaneous: Fever (4% to 18%)
1% to 10%:
Gastrointestinal: Increased serum lipase (>3 times ULN: ≤2%)
Hematologic & oncologic: Thrombocytopenia (≤1%)
Hepatic: Increased serum bilirubin (>2.5 times ULN: 3%)
Renal: Increased creatine phosphokinase in blood specimen (≥10 times ULN: 1% to 2%)
<1%:
Hematologic & oncologic: Pancytopenia
Nervous system: Severe depression, suicidal ideation
Postmarketing:
Cardiovascular: Bradycardia
Dermatologic: Stevens-Johnson syndrome (Verma 2017)
Endocrine & metabolic: Lactic acidosis (Smith 2019)
Hypersensitivity: Angioedema
Infection: Reactivation of HBV
There are no contraindications listed in the manufacturer's labeling. When administered with ribavirin and peginterferon alfa, the contraindications to ribavirin and peginterferon alfa also apply. See Ribavirin and Peginterferon Alfa monographs.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to sofosbuvir or any component of the formulation; males whose female partners may become pregnant
Disease-related concerns:
• Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic therapy may be necessary (Ciancio 2018; Dawood 2017; Hum 2017).
• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV co-infected patients who were receiving or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy; some cases have resulted in fulminant hepatitis, hepatic failure, and death. Test all patients for evidence of current or prior HBV infection prior to initiation of sofosbuvir; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.
Concurrent drug therapy issues:
• Amiodarone: Symptomatic bradycardia (some requiring pacemaker intervention) has occurred in patients receiving amiodarone and a sofosbuvir-containing regimen. Fatal cardiac arrest occurred in a patient taking amiodarone and the ledipasvir/sofosbuvir combination product. Bradycardia generally occurred within hours to days following coadministration, however some cases have occurred 2 weeks following the initiation of sofosbuvir. The risk of bradycardia may be increased in patients taking beta blockers or patients with underlying cardiac comorbidities and/or advanced liver disease. Bradycardia generally resolves following discontinuation of HCV treatment. Coadministration of amiodarone and sofosbuvir in combination with another DAA is not recommended. However, if patients have no treatment alternatives, patients should have inpatient cardiac monitoring for the first 48 hours, followed by daily outpatient or self-monitoring of heart rate for at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, cardiac monitoring (as described) is also recommended if amiodarone was discontinued just prior to beginning treatment with sofosbuvir. Patients should seek medical attention immediately if they experience fainting or near-fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pains, confusion or memory problems.
Special populations:
• Hepatic impairment: Safety and efficacy have not been established in patients with decompensated cirrhosis.
Other warnings/precautions:
• Appropriate use: Do not use as monotherapy; use only as part of a multiple drug regimen for treatment of HCV; consult current HCV treatment guidelines for guidance (AASLD/IDSA 2021).
Sovaldi oral pellets: FDA approved August 2019; anticipated availability is currently unknown. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Sovaldi: 150 mg (28 ea); 200 mg (28 ea)
Tablet, Oral:
Sovaldi: 200 mg, 400 mg
No
Pack (Sovaldi Oral)
150 mg (per each): $1,200.00
200 mg (per each): $1,200.00
Tablets (Sovaldi Oral)
200 mg (per each): $1,200.00
400 mg (per each): $1,200.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sovaldi: 400 mg
Oral:
Pellets: Administer with or without food. May be sprinkled on 1 or more spoonfuls of non-acidic soft foods (eg, pudding, chocolate syrup, mashed potatoes, ice cream) at or below room temperature; gently mix. Swallow entire contents within 30 minutes of mixing; to avoid bitter aftertaste, do not chew.
Tablets: Administer with or without food.
Oral:
Tablets: Administer with or without food.
Pellets: Administer with or without food. If administered without food, pour packet contents directly in the mouth and swallow without chewing to avoid bitter aftertaste; follow with water if needed. If administered with food, sprinkle packet contents on ≥1 spoonfuls of non-acidic soft foods (eg, pudding, chocolate syrup, mashed potatoes, ice cream) at or below room temperature; gently mix. Swallow entire contents within 30 minutes of mixing; do not chew to avoid bitter aftertaste.
Tablets and pellets: Store below 30°C (86°F). Dispense only in original packaging.
Treatment of genotype 2 or 3 chronic hepatitis C virus (HCV) infection, in combination with ribavirin, in patients without cirrhosis or with compensated cirrhosis (FDA approved in pediatric patients ≥3 years); treatment of genotype 1, 2, 3, or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen (FDA approved in adults).
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amiodarone: Sofosbuvir may enhance the bradycardic effect of Amiodarone. Management: Use alternative to a sofosbuvir-containing combo or to amiodarone when possible. If alternatives not possible, monitor in inpatient setting for first 48 hours of coadministration with daily outpatient monitoring for at least 2 weeks. Risk D: Consider therapy modification
Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Atorvastatin: Sofosbuvir may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapy
Modafinil: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
OXcarbazepine: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Rifabutin: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Tacrolimus (Systemic): Direct Acting Antiviral Agents (HCV) may decrease the serum concentration of Tacrolimus (Systemic). Direct Acting Antiviral Agents (HCV) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Patients with hepatitis C virus (HCV) infection should be treated before considering pregnancy to optimize maternal health and reduce the risk of HCV transmission (AASLD/IDSA 2021).
Sofosbuvir is not used as monotherapy; if used in combination with ribavirin or peginterferon, all warnings related to the use of ribavirin or peginterferon and contraception should be followed. Refer to the ribavirin and peginterferon monographs for additional information.
Based on a placental perfusion study, GS-331007 (the main metabolite of sofosbuvir) is expected to cross the placenta (Freriksen 2020).
Sofosbuvir is not used as monotherapy; combination therapy with ribavirin is contraindicated in pregnant patients and males whose partners are pregnant. If used in combination with ribavirin or peginterferon, all warnings related to the use of ribavirin or peginterferon and pregnancy should be followed. Refer to the ribavirin and peginterferon monographs for additional information.
Outcome data following maternal use of sofosbuvir and other direct-acting antiviral (DAA) medications during pregnancy are limited. Use of a DAA is not currently recommended for the purpose of reducing mother to child transmission of hepatitis C virus due to a lack of safety and efficacy data. The decision to continue treatment in a patient who becomes pregnant while taking a DAA should be individualized after considering the potential benefits and risks of therapy. DAA medications should not be initiated during pregnancy outside of clinical trials until safety and efficacy data are available (AASLD/IDSA 2021; AbdAllah 2021; Mandimika 2019; SMFM [Dotters-Katz 2021]).
Management of hepatitis C virus (HCV) infection requires extensive monitoring; refer to current guidelines for additional guidance including response to abnormal laboratory parameters (AASLD/IDSA 2018).
Baseline (within 12 weeks prior to starting antiviral therapy): CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), SCr, calculated GFR. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) prior to initiation; in patients with serologic evidence of hepatitis B virus (HBV) infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during post-treatment follow-up. HCV genotype and subtype, quantitative HCV viral load (at any time prior to starting antiviral therapy) (AASLD/IDSA 2018).
During therapy: CBC, SCr, calculated GFR, hepatic function panel (after 4 weeks of therapy and as clinically indicated); quantitative HCV viral load testing (after 4 weeks of therapy and at 12 weeks after completion of therapy). If quantitative HCV viral load is detectable at treatment week 4, repeat testing is recommended after 2 additional weeks of treatment (treatment week 6) (AASLD/IDSA 2018). If used in combination with amiodarone (or in patients who discontinued amiodarone just prior to initiating sofosbuvir), inpatient cardiac monitoring for the first 48 hours of coadministration, then daily outpatient or self-monitoring of heart rate through at least the first 2 weeks of treatment.
Sofosbuvir, a direct-acting antiviral agent against the hepatitis C virus, is a prodrug converted to its pharmacologically active form (GS-461203) via intracellular metabolism. It inhibits HCV NS5B RNA-dependent RNA polymerase, essential for viral replication, and acts as a chain terminator.
Note: The pharmacokinetic profile in pediatric patients ≥3 years of age is similar to adult patients.
Protein binding: ~61% to 65%
Metabolism: Hepatic; forms pharmacologically active nucleoside (uridine) analog triphosphate GS-461203; dephosphorylation results in the formation of nucleoside inactive metabolite GS-331007
Half-life elimination: 0.4 hours
Time to peak: ~0.5 to 2 hours
Excretion: Urine (80%; primarily as metabolite); feces (14%)
Altered kidney function: AUC0-∞ was higher in mild (eGFR ≥50 and <80 mL/minute/1.73 m2), moderate (eGFR ≥30 and <50 mL/minute/1.73 m2), and severe (eGFR <30 mL/minute/1.73 m2) renal impairment.
Hepatic function impairment: AUC0-24 was higher in moderate and severe hepatic impairment.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟