Pronunciation:

le-DIP-as-vir, soe-FOS-bue-vir

Brand Names:

• Harvoni

Dosage Forms:

• Packet
• Tablet

Warnings:

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ledipasvir/sofosbuvir. HBV reactivation has been reported in HCV/HBV coinfected 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 coinfected 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 .

Classifications:

Therapeutic—

Antiviral

Pharmacologic—

Hepatitis C Virus NS5A Inhibitor

Uses of This Medicine:

Ledipasvir and sofosbuvir combination is used with or without ribavirin to treat chronic hepatitis C infection in adults and children 3 years of age and older (including liver transplant patients, with or without cirrhosis).

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of ledipasvir and sofosbuvir combination in children younger than 3 years of age. Safety and efficacy have not been established.

Older adults—

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.

Other 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 this medicine, 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 this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rifampin

Using this medicine 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.

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

Other interactions—

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.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease or
• Liver disease, advanced—May increase risk for bradycardia (slow heartbeat).

• Hepatitis B infection, history of—Use with caution. May cause this disease to become active again.

• Kidney disease, severe—It is not known if this medicine will work in patients with this condition.

• Liver problems or
• Liver transplant, history of—Use with caution. May make these conditions worse.

Proper Use of This Medicine:

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a patient information leaflet. Read and follow the information carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

If you are using the oral pellets:

• Do not open the packet until ready to use. Do not use a packet if the seal is broken or damaged.
• Hold the packet with the cut line on top and shake it gently to settle the pellets.
• Tear or cut the packet along the cut line.
• Swallow the oral pellets with water. Do not crush or chew them.
• If the oral pellets are taken with food, sprinkle the pellets on 1 or more spoonfuls of non-acidic soft food (eg, pudding, chocolate syrup, mashed potato, and ice cream) at or below room temperature.
• Swallow the mixture right away (within 30 minutes). Do not save any of the mixture to use later.

To help clear up your infection completely, ledipasvir and sofosbuvir combination must be taken for the full time of treatment, even if you begin to feel better after a few days. Also, it is important to keep the amount of medicine in your body at a steady level. To help keep the amount constant, this medicine must be used on a regular schedule.

If you are taking an antacid containing aluminum or magnesium hydroxide, take it 4 hours before or after taking ledipasvir and sofosbuvir combination.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (pellets or tablets):
  • For hepatitis C virus infection:
    • Adults—1 tablet once a day, taken for 12 or 24 weeks. Each tablet contains ledipasvir 90 milligrams (mg) and sofosbuvir 400 mg.
    • Children 3 years of age and older weighing at least 35 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. The dose is usually 1 tablet (containing ledipasvir 90 mg and sofosbuvir 400 mg) once a day, or two tablets (containing ledipasvir 45 mg and 200 mg sofosbuvir) once a day, or two packets of pellets (containing ledipasvir 45 mg and 200 mg sofosbuvir) once a day, taken for 12 or 24 weeks.
    • Children 3 years of age and older weighing 17 to less than 35 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually one tablet (containing ledipasvir 45 mg and 200 mg sofosbuvir) once a day, or one packet of pellets (containing ledipasvir 45 mg and 200 mg sofosbuvir) once a day, taken for 12 or 24 weeks.
    • Children 3 years of age and older weighing less than 17 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually one packet of pellets (containing ledipasvir 33.75 mg and 150 mg sofosbuvir) once a day, taken for 12 or 24 weeks.
    • Children younger than 3 years of age—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the medicine in the original container.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine together with ribavirin while you are pregnant can harm your unborn baby. These medicines may also cause birth defects if the father is using it when his sexual partner becomes pregnant. If a pregnancy occurs while you are using these medicines and for 6 months after your treatment ends, tell your doctor right away.

Using this medicine with amiodarone may cause bradycardia. Check with your doctor right away if you have chest pain or discomfort, lightheadedness, dizziness, or fainting, shortness of breath, slow or uneven heartbeat, or unusual tiredness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

Chest pain or discomfort

lightheadedness, dizziness, or fainting

slow or irregular heartbeat

trouble breathing

unusual tiredness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Cough

diarrhea

headache

irritability

lack or loss of strength

muscle pain

nausea

trouble sleeping

Less common

Discouragement

dizziness

feeling sad or empty

lack of appetite

loss of interest or pleasure

trouble concentrating

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.