Ledipasvir and sofosbuvir

Name: Ledipasvir and sofosbuvir

Ledipasvir and sofosbuvir missed dose
Ledipasvir and sofosbuvir dosage
Ledipasvir and sofosbuvir drug
Ledipasvir and sofosbuvir adverse effects
Ledipasvir and sofosbuvir 40 mg
Ledipasvir and sofosbuvir therapeutic effect
Ledipasvir and sofosbuvir effects of ledipasvir and sofosbuvir
Ledipasvir and sofosbuvir the effects of ledipasvir and sofosbuvir
Ledipasvir and sofosbuvir how to take
Ledipasvir and sofosbuvir side effects
Ledipasvir and sofosbuvir uses
Ledipasvir and sofosbuvir names

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Cautions for Ledipasvir and Sofosbuvir

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

If ledipasvir/sofosbuvir used in conjunction with ribavirin, the contraindications to ribavirin also apply.1 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Rash, sometimes with blisters or angioedema-like swelling, reported during postmarketing experience.1

Cardiovascular Effects

Postmarketing reports of symptomatic bradycardia, including cases requiring pacemaker intervention, in patients receiving amiodarone concomitantly with ledipasvir/sofosbuvir.1 23 Fatal cardiac arrest reported in one patient.1

In most reported cases, bradycardia occurred within hours to days after HCV treatment initiated in patients receiving amiodarone (also has been observed up to 2 weeks after initiation of HCV treatment) and resolved after HCV treatment discontinued.1 Mechanism for this adverse cardiovascular effect unknown.1

Patients who may be at increased risk for symptomatic bradycardia if amiodarone used concomitantly with ledipasvir/sofosbuvir include those also receiving a β-adrenergic blocking agent, those with underlying cardiac comorbidities, and/or those with advanced liver disease.1

Concomitant use of amiodarone with ledipasvir/sofosbuvir not recommended.1

If there are no alternative HCV treatment options and regimen of ledipasvir/sofosbuvir must be used in a patient receiving amiodarone, advise patient about the risk of serious bradycardia before initiating HCV treatment.1 Perform cardiac monitoring in an inpatient setting during first 48 hours of concomitant use of amiodarone and ledipasvir/sofosbuvir;1 heart rate monitoring should then be performed daily (outpatient or self-monitoring) through at least the first 2 weeks of concomitant use.1 Similar cardiac monitoring recommended in patients who discontinued amiodarone just prior to initiation of ledipasvir/sofosbuvir or if there are no other treatment options and amiodarone must be initiated in a patient already receiving ledipasvir/sofosbuvir.1

Advise patients receiving amiodarone concomitantly with ledipasvir/sofosbuvir to immediately contact a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) develop.1

Interactions

Concomitant use of ledipasvir/sofosbuvir and inducers of the P-glycoprotein (P-gp) transport system (e.g., rifampin, St. John's wort) not recommended.1 (See Interactions.)

Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens

Consider cautions, precautions, contraindications, and drug interactions associated with both drugs in the fixed combination.1 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for both ledipasvir and sofosbuvir.1

Do not use ledipasvir/sofosbuvir concomitantly with any other preparation containing sofosbuvir.1

When used in conjunction with ribavirin, consider that ribavirin may cause fetal toxicity and/or death.349 377 Extreme care must be taken to avoid pregnancy in female patients and female partners of male patients receiving a ribavirin-containing regimen.349 377 Obtain a negative pregnancy test for female patients of childbearing potential immediately prior to initiating ribavirin;349 377 perform pregnancy tests monthly during and for 6 months after ribavirin treatment is completed.349 377 Women of childbearing potential (and their male partners) and male patients (and their female partners) must use at least 2 forms of effective contraception during and for 6 months after ribavirin treatment is completed.349 377

Specific Populations

Pregnancy

Adequate data regarding use of ledipasvir/sofosbuvir in pregnant women not available.1 In animal studies, neither ledipasvir nor sofosbuvir affected fetal development at dosages tested.1

When used in conjunction with ribavirin, consider that ribavirin is contraindicated in pregnant women and male partners of pregnant women.1 349 377 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

Lactation

Not known whether ledipasvir/sofosbuvir and metabolites distributed into human milk.1

Predominant metabolite of sofosbuvir (GS-331007) distributed into milk in rats;1 ledipasvir detected in plasma of suckling rat pups.1 No apparent effects on the nursing pups.1

Consider benefits of breast-feeding and importance of the drug to the woman;1 also consider potential adverse effects on the breast-fed child from the drug or underlying maternal condition.1

When used in conjunction with ribavirin,1 consider potential for adverse reactions to ribavirin in nursing infants and discontinue nursing or the ribavirin-containing regimen.349 377 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

No overall differences in safety and efficacy in patients ≥65 years of age compared with younger adults,1 but increased sensitivity in some older individuals cannot be ruled out.1

Hepatic Impairment

Severe hepatic impairment (Child-Pugh class C) without HCV infection: Ledipasvir exposure similar to exposure in individuals similar to exposure in individuals with normal hepatic function.1

HCV-infected individuals with moderate or severe hepatic impairment (Child-Pugh class B or C): Increased sofosbuvir and GS-331007 exposures compared with exposures in individuals with normal hepatic function.1

When ledipasvir/sofosbuvir is used in conjunction with ribavirin in patients with decompensated cirrhosis (Child-Pugh class B or C), clinical and hepatic laboratory monitoring is recommended as clinically indicated.1

Renal Impairment

Severe renal impairment (estimated GFR <30 mL/minute per 1.73 m2) or ESRD requiring hemodialysis: Safety and efficacy not established.1

Severe renal impairment without HCV infection: Ledipasvir exposure similar to exposure in healthy individuals;1 substantially increased sofosbuvir and GS-331007 exposures compared with exposures in individuals with normal renal function.1

HCV-infected with HIV Coinfection

Safety profile of ledipasvir/sofosbuvir in individuals with HCV genotype 1 or genotype 4 infection and HIV-1 coinfection generally comparable to that reported in HCV-infected individuals without HIV-1 coinfection.1

Common Adverse Effects

Ledipasvir/sofosbuvir: Fatigue,1 2 3 4 9 10 headache,1 2 3 4 9 10 nausea,1 2 3 4 9 diarrhea,1 2 3 4 9 10 abdominal pain,10 insomnia or sleep disorder,1 2 3 4 9 irritability,1 2 9 rash,2 4 pruritus,2 dry skin,9 arthralgia,3 4 9 10 myalgia,1 9 10 back pain,9 asthenia,2 9 10 cough,1 2 4 9 10 upper respiratory tract infection,4 9 10 dizziness.1 4 10

Ledipasvir/sofosbuvir in conjunction with ribavirin: Fatigue,9 headache,1 9 nausea,9 diarrhea,9 insomnia,9 asthenia,1 9 cough,1 9 bronchitis,9 dyspnea,1 irritability,1 9 pruritus,9 dry skin,9 myalgia,9 decreased hemoglobin.1

Interactions for Ledipasvir and Sofosbuvir

Ledipasvir inhibits P-gp transport system.1 Ledipasvir and sofosbuvir are substrates of P-gp.1

Ledipasvir inhibits breast cancer resistance protein (BCRP).1 Ledipasvir and sofosbuvir are substrates of BCRP.1

At concentrations exceeding those achieved in clinical settings, ledipasvir inhibits organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and the bile salt export pump (BSEP).1

The following drug interactions are based on studies using ledipasvir/sofosbuvir, ledipasvir alone, or sofosbuvir alone.1 When ledipasvir/sofosbuvir used, consider interactions associated with both drugs in the fixed combination.1

Drugs Affecting or Affected by P-glycoprotein Transport System

P-gp substrates: Concomitant use of ledipasvir and P-gp substrates may increase intestinal absorption of such drugs.1

P-gp inducers: Possible decreased ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect.1 Concomitant use not recommended.1

Drugs Affecting or Affected by Breast Cancer Resistance Protein

BCRP substrates: Concomitant use of ledipasvir and BCRP substrates may increase intestinal absorption of such drugs.1

Inhibitors of BCRP: Possible increased plasma concentrations of ledipasvir and sofosbuvir without increase in plasma concentrations of GS-331007.1

Specific Drugs

Drug	Interaction	Comments
Abacavir	Abacavir: Clinically important pharmacokinetic interactions not expected1 Fixed combination of abacavir and lamivudine (abacavir/lamivudine): No clinically important effects on pharmacokinetics of abacavir, lamivudine, ledipasvir, or sofosbuvir8
Antacids (aluminum, magnesium hydroxide)	Decreased ledipasvir concentrations expected;1 increased gastric pH decreases ledipasvir solubility1	Take antacids 4 hours before or after ledipasvir/sofosbuvir1
Antiarrhythmic agents (amiodarone)	Amiodarone: Concomitant use with ledipasvir/sofosbuvir may result in serious symptomatic bradycardia1 23 (mechanism unknown);1 effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown1	Amiodarone: Concomitant use with ledipasvir/sofosbuvir not recommended;1 if concomitant use required, patient counseling and cardiac monitoring required1 (see Cardiovascular Effects under Cautions)
Anticonvulsants (carbamazepine, oxcarbazepine, phenytoin, phenobarbital)	Carbamazepine, oxcarbazepine, phenytoin, phenobarbital: Decreased ledipasvir and sofosbuvir concentrations expected;1 may lead to reduced therapeutic effect1	Carbamazepine, oxcarbazepine, phenytoin, phenobarbital: Concomitant use with ledipasvir/sofosbuvir not recommended1
Antimycobacterial agents (rifabutin, rifampin, rifapentine)	Rifabutin, rifampin, rifapentine: Decreased ledipasvir and sofosbuvir concentrations expected;1 may lead to reduced therapeutic effect1	Rifabutin, rifampin, rifapentine: Concomitant use with ledipasvir/sofosbuvir not recommended1
Atazanavir	Ritonavir-boosted atazanavir: Increased atazanavir and ledipasvir AUCs; no clinically important effects on pharmacokinetics of sofosbuvir1 200 Fixed combination of atazanavir and cobicistat (atazanavir/cobicistat): Clinically important pharmacokinetic interactions not expected200 HIV antiretroviral regimens that include tenofovir disoproxil fumarate (tenofovir DF) and ritonavir-boosted atazanavir or atazanavir/cobicistat: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;1 200 safety of increased tenofovir concentrations not established1	Ritonavir-boosted atazanavir: Dosage adjustments not needed200 Atazanavir/cobicistat: Dosage adjustments not needed200 HIV antiretroviral regimens that include tenofovir DF and ritonavir-boosted atazanavir or atazanavir/cobicistat: Consider alternative HCV treatment or alternative antiretroviral therapy;1 200 if concomitant use necessary, monitor for tenofovir-associated adverse effects1 200
Darunavir	Ritonavir-boosted darunavir: No clinically important effects on pharmacokinetics of darunavir, ritonavir, ledipasvir, or sofosbuvir1 200 Fixed combination of darunavir and cobicistat (darunavir/cobicistat): Clinically important pharmacokinetic interactions not expected200 HIV antiretroviral regimens that include tenofovir DF and ritonavir-boosted darunavir or darunavir/cobicistat: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;1 200 safety of increased tenofovir concentrations not established1	Ritonavir-boosted darunavir: Dosage adjustments not needed200 Darunavir/cobicistat: Dosage adjustments not needed200 HIV antiretroviral regimens that include tenofovir DF and ritonavir-boosted darunavir or darunavir/cobicistat: Consider alternative HCV treatment or alternative antiretroviral therapy;1 200 if concomitant use necessary, monitor for tenofovir-associated adverse effects1 200
Digoxin	Possible increased digoxin concentrations1	Therapeutic concentration monitoring of digoxin recommended1
Dolutegravir	Dolutegravir: Clinically important pharmacokinetic interactions not expected1 HIV antiretroviral regimen of dolutegravir in conjunction with fixed combination of emtricitabine and tenofovir DF (emtricitabine/tenofovir DF): Increased tenofovir concentrations and AUC expected1
Efavirenz	Efavirenz: Possible decreased concentrations and AUC of ledipasvir;200 no clinically important effects on sofosbuvir or efavirenz pharmacokinetics1 200 Fixed combination of efavirenz, emtricitabine, and tenofovir DF (efavirenz/emtricitabine/tenofovir DF): Decreased ledipasvir concentrations and AUC and increased tenofovir concentrations and AUC;1 200 no clinically important effects on pharmacokinetics of efavirenz or sofosbuvir1 200	Efavirenz: Dosage adjustments not needed if efavirenz and ledipasvir/sofosbuvir used concomitantly200 HIV antiretroviral regimen that includes efavirenz in conjunction with emtricitabine and tenofovir DF: Monitor for tenofovir-associated adverse effects200
Elvitegravir	Elvitegravir with cobicistat (cobicistat-boosted elvitegravir): Increased concentrations and AUC of ledipasvir and cobicistat;8 no clinically important effects on pharmacokinetics of elvitegravir or sofosbuvir8 Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir DF (EFV/c/FTC/TDF): Increased tenofovir and ledipasvir concentrations expected;1 200 safety of increased tenofovir concentrations not established1 Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (EFV/c/FTC/TAF): No clinically important effects on any of the drugs1 Single-entity elvitegravir used in conjunction with a ritonavir-boosted HIV PI: Clinically important effect on elvitegravir concentrations not expected200	EVG/c/FTC/TDF: Concomitant use with ledipasvir/sofosbuvir not recommended1 200 Single-entity elvitegravir used in conjunction with a ritonavir-boosted HIV PI: Refer to dosage recommendations for the HIV PI200
Emtricitabine	Clinically important pharmacokinetic interactions not expected1
Estrogens/progestins	Oral contraceptive containing ethinyl estradiol and norgestimate: No clinically important effects on pharmacokinetics of ethinyl estradiol or norgestimate and its active metabolites (norelgestromin, norgestrel) when used concomitantly with ledipasvir or sofosbuvir;1 7 efficacy of the oral contraceptive not expected to be affected7
Etravirine	Clinically important interactions not expected200	Dosage adjustments not needed if etravirine and ledipasvir/sofosbuvir used concomitantly200
Fosamprenavir	HIV antiretroviral regimens that include ritonavir-boosted fosamprenavir and tenofovir DF: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;200 safety of increased tenofovir concentrations not established1	HIV antiretroviral regimens that include ritonavir-boosted fosamprenavir and tenofovir DF: Consider alternative HCV treatment or alternative antiretroviral therapy;200 if concomitant use necessary, monitor for tenofovir-associated adverse effects200
Histamine H2-receptor antagonists	Decreased ledipasvir concentrations expected;1 increased gastric pH decreases ledipasvir solubility1	Administer H2-antagonists concomitantly with or 12 hours apart from ledipasvir/sofosbuvir;1 do not exceed H2-antagonist dosages comparable to famotidine 40 mg twice daily1
HMG-CoA reductase inhibitors (statins)	Pravastatin: Clinically important interactions not expected1 Rosuvastatin: Possible increased rosuvastatin concentrations and increased risk of myopathy and rhabdomyolysis1	Rosuvastatin: Concomitant use with ledipasvir/sofosbuvir not recommended1
Immunosuppressants (cyclosporine, tacrolimus)	Cyclosporine: Pharmacokinetics of cyclosporine not affected by ledipasvir or sofosbuvir;1 clinically important interactions not expected if used with ledipasvir/sofosbuvir1 Tacrolimus: Clinically important interactions not expected1
Lamivudine	Lamivudine: Clinically important pharmacokinetic interactions not expected1 Abacavir/lamivudine: No clinically important effects on pharmacokinetics of abacavir, lamivudine, ledipasvir, or sofosbuvir8
Lopinavir	HIV antiretroviral regimens that include fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) and tenofovir DF: Possible increased tenofovir concentrations if used concomitantly with ledipasvir/sofosbuvir;1 200 safety of increased tenofovir concentrations not established1	HIV antiretroviral regimens that include lopinavir/ritonavir and tenofovir DF: Consider alternative HCV treatment or alternative antiretroviral therapy;1 200 if concomitant use necessary, monitor for tenofovir-associated adverse effects1 200
Maraviroc	Clinically important effect on maraviroc pharmacokinetics not expected200	Some experts recommend maraviroc 300 mg twice daily in those receiving ledipasvir/sofosbuvir200
Methadone	Methadone pharmacokinetics not affected by ledipasvir or sofosbuvir;1 clinically important interactions not expected if used with ledipasvir/sofosbuvir1
Nevirapine	Clinically important drug interactions not expected200	Dosage adjustments not needed if nevirapine and ledipasvir/sofosbuvir used concomitantly200
Proton-pump inhibitors	Decreased ledipasvir concentrations expected;1 increased gastric pH decreases ledipasvir solubility1	Administer proton-pump inhibitors concomitantly with ledipasvir/sofosbuvir under fasting conditions;1 do not exceed proton-pump inhibitor dosages comparable to 20 mg of omeprazole once daily1
Raltegravir	No clinically important effects on pharmacokinetics of raltegravir, ledipasvir, or sofosbuvir1
Rilpivirine	Rilpivirine: No clinically important effects on pharmacokinetics of rilpivirine, ledipasvir, or sofosbuvir1 Fixed combination of emtricitabine, rilpivirine, and tenofovir DF (emtricitabine/rilpivirine/tenofovir DF): Increased tenofovir concentrations and AUC1 200	Rilpivirine: Dosage adjustments not needed if rilpivirine and ledipasvir/sofosbuvir used concomitantly200 HIV antiretroviral regimens that include emtricitabine/rilpivirine/tenofovir DF: Monitor for tenofovir-associated adverse effects200
Saquinavir	HIV antiretroviral regimens that include ritonavir-boosted saquinavir and tenofovir DF: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;200 safety of increased tenofovir concentrations not established1	HIV antiretroviral regimens that include ritonavir-boosted saquinavir and tenofovir DF: Consider alternative HCV treatment or alternative antiretroviral therapy;200 if concomitant use necessary, monitor for tenofovir-associated adverse effects200
Simeprevir	Increased ledipasvir and simeprevir concentrations1	Concomitant use of ledipasvir/sofosbuvir and simeprevir not recommended1
Sofosbuvir		Do not use ledipasvir/sofosbuvir with any other preparation containing sofosbuvir1
St. John's wort (Hypericum perforatum)	Decreased ledipasvir and sofosbuvir concentrations;1 may result in loss of therapeutic effect of ledipasvir/sofosbuvir1	Concomitant use with ledipasvir/sofosbuvir not recommended1
Tenofovir	EVG/c/FTC/TDF: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;1 safety of increased tenofovir concentrations not established1 HIV antiretroviral regimens that include tenofovir DF and a ritonavir-boosted HIV PI, atazanavir/cobicistat, or darunavir/cobicistat: Possible increased tenofovir concentrations if used with ledipasvir/sofosbuvir;1 200 safety of increased tenofovir concentrations not established1	EVG/c/FTC/TDF: Concomitant use with ledipasvir/sofosbuvir not recommended1 200 HIV antiretroviral regimens that include tenofovir DF and a ritonavir-boosted HIV PI, atazanavir/cobicistat, or darunavir/cobicistat: Consider alternative HCV treatment or alternative antiretroviral therapy;1 200 if concomitant use necessary, monitor for tenofovir-associated adverse effects1 200 HIV antiretroviral regimens that include tenofovir DF without a ritonavir-boosted HIV PI or cobicistat: Monitor for tenofovir-associated adverse effects1 200
Tipranavir	Ritonavir-boosted tipranavir: Decreased concentrations of ledipasvir and sofosbuvir expected;1 may lead to reduced therapeutic effect of ledipasvir/sofosbuvir1	Ritonavir-boosted tipranavir: Concomitant use with ledipasvir/sofosbuvir not recommended1 200
Verapamil	Clinically important interactions not expected1

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Advise patients to take ledipasvir/sofosbuvir once daily (with or without food) on a regular dosing schedule.1
Importance of taking recommended dosage of ledipasvir/sofosbuvir for the recommended duration of treatment;1 importance of not missing or skipping doses.1
If ledipasvir/sofosbuvir is used in a patient receiving amiodarone, advise patient about the risk of serious symptomatic bradycardia and importance of immediately contacting clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness, lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) occur.1 (See Cardiovascular Effects under Cautions.)
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 If ledipasvir/sofosbuvir is used in conjunction with ribavirin, advise men and women of importance of using 2 forms of effective contraception during and for 6 months after ribavirin therapy.349 377 (See Precautions Related to Fixed Combinations and Multiple-drug Treatment Regimens under Cautions.)
Importance of informing patients of other important precautionary information.1 (See Cautions.)

Before Using ledipasvir and sofosbuvir

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For ledipasvir and sofosbuvir, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to ledipasvir and sofosbuvir or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of ledipasvir and sofosbuvir combination in children younger than 12 years of age and weighing less than 35 kg. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ledipasvir and sofosbuvir combination in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking ledipasvir and sofosbuvir, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using ledipasvir and sofosbuvir with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Aluminum Carbonate, Basic
Aluminum Hydroxide
Aluminum Phosphate
Amiodarone
Calcium Carbonate
Carbamazepine
Cimetidine
Dexlansoprazole
Digoxin
Dihydroxyaluminum Aminoacetate
Dihydroxyaluminum Sodium Carbonate
Esomeprazole
Famotidine
Fosphenytoin
Lansoprazole
Magaldrate
Magnesium Carbonate
Magnesium Hydroxide
Magnesium Oxide
Magnesium Trisilicate
Nizatidine
Omeprazole
Oxcarbazepine
Pantoprazole
Phenobarbital
Phenytoin
Rabeprazole
Ranitidine
Rifabutin
Rifampin
Rifapentine
Rosuvastatin
Simeprevir
Sodium Bicarbonate
St John's Wort
Tenofovir Disoproxil Fumarate
Tipranavir
Topotecan

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

How is this medicine (Ledipasvir and Sofosbuvir) best taken?

Use ledipasvir and sofosbuvir as ordered by your doctor. Read all information given to you. Follow all instructions closely.

Take with or without food.
Do not take antacids within 4 hours of this medicine.
If you take cimetidine, dexlansoprazole, esomeprazole, famotidine, lansoprazole, nizatidine, omeprazole, pantoprazole, rabeprazole, or ranitidine, ask your doctor or pharmacist how to take it with ledipasvir and sofosbuvir.
Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
It is important that you do not miss or skip a dose of ledipasvir and sofosbuvir during treatment.

What do I do if I miss a dose?

Take a missed dose as soon as you think about it.
If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
Do not take 2 doses at the same time or extra doses.
If you are not sure what to do if you miss a dose, call your doctor.

What are some side effects that I need to call my doctor about right away?

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.
Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

If your symptoms or health problems do not get better or if they become worse, call your doctor.
Do not share your drugs with others and do not take anyone else's drugs.
Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take ledipasvir and sofosbuvir or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to ledipasvir and sofosbuvir. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Brand Names U.S.

Harvoni

Dosing Geriatric

Refer to adult dosing.

Dosing Renal Impairment

eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling. However, sofosbuvir and metabolite accumulate in patients with severely impaired renal function.

End-stage renal disease (ESRD) , including those requiring intermittent hemodialysis (IHD): There are no dosage adjustments provided in the manufacturer's labeling However, sofosbuvir and metabolite accumulate in patients with severely impaired renal function. In a 4-hour dialysis session, 18% of sofosbuvir dose was removed.

Monitoring Parameters

Manufacturer’s labeling:

Bilirubin, liver enzymes, and serum creatinine at baseline and periodically when clinically indicated. If used in combination with amiodarone (or in patients who discontinued amiodarone just prior to initiating ledipasvir/sofosbuvir), inpatient cardiac monitoring for the first 48 hours of coadministration, then outpatient or self-monitoring of heart rate daily through at least the first 2 weeks of treatment.

Serum HCV-RNA at baseline, during treatment, at the end of treatment, during treatment follow-up, and when clinically indicated.

Hepatitis B surface antigen (HBsAg) 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.

Alternate recommendations (AASLD/IDSA 2015):

Baseline (within 12 weeks prior to starting antiviral therapy): CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), calculated GFR

Baseline (at any time prior to starting antiviral therapy): HCV genotype and subtype, quantitative HCV viral load

During therapy: CBC, serum creatinine, 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).