Ledipasvir with sofosbuvir oral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of ledipasvir with sofosbuvir.
Drugs List
Therapeutic Indications
Uses
Hepatitis C - chronic
Dosage
Dependent on the hepatitis C virus (HCV) genotype and level of hepatic disease, combination with ribavirin may be required.
The monograph for ribavirin should also be consulted as additional dose modifications may be required in some patient populations.
Adults
90mg ledipasvir and 400mg sofosbuvir, taken once daily.
In adults, ribavirin should be prescribed in line with current manufacturer recommendations (consult product information for details).
Treatment regimen and duration:
Chronic hepatitis C: HCV genotype 1, 4, 5, or 6
Patients without cirrhosis:
Ledipasvir with sofosbuvir (without ribavirin) for 12 weeks. 8 weeks may be considered in patients with previously untreated HCV genotype 1.
Patients with compensated cirrhosis:
Ledipasvir with sofosbuvir combined with ribavirin for 12 weeks or ledipasvir with sofosbuvir (without ribavirin) for 24 weeks.
Ledipasvir with sofosbuvir (without ribavirin) for 12 weeks may be considered for patients at low risk for clinical disease progression with subsequent re-treatment options.
Patients who are post-liver transplant without cirrhosis:
Ledipasvir with sofosbuvir combined with ribavirin for 12 weeks.
Ledipasvir with sofosbuvir (without ribavirin) for 12 weeks may be considered in patients ineligible for or intolerant to ribavirin.
Patients who are post-liver transplant with compensated cirrhosis:
Ledipasvir with sofosbuvir combined with ribavirin for 12 weeks.
Ledipasvir with sofosbuvir (without ribavirin) for 24 weeks may be considered in patients ineligible for or intolerant to ribavirin.
Patients with decompensated cirrhosis (irrespective of transplant status):
Ledipasvir with sofosbuvir combined with ribavirin for 12 weeks.
Ledipasvir with sofosbuvir (without ribavirin) for 24 weeks may be considered in patients ineligible for or intolerant to ribavirin.
Dose modifications for ribavirin apply in this patient group (see Dosage; Hepatic Impairment).
Chronic hepatitis C: HCV genotype 3
Patients with compensated cirrhosis and/or prior treatment failure:
Ledipasvir with sofosbuvir combined with ribavirin for 24 weeks.
Children
Children aged 3 to 18 years:
When used in children, recommended doses of ribavirin are based on the medicinal product that it is combined with. Consult the product information for ledipasvir with sofosbuvir for standard recommended doses.
Body weight greater than or equal to 35kg
90mg ledipasvir and 400mg sofosbuvir, taken once daily.
The recommended treatment regimen and duration should follow adult guidelines (see Dosage; Adult).
Body weight between 17kg and 35kg
45mg ledipasvir and 200mg sofosbuvir, taken once daily.
The recommended treatment regimen and duration should follow adult guidelines (see Dosage; Adult).
Body weight lower than 17kg
33.75mg ledipasvir and 150mg sofosbuvir, taken once daily.
The recommended treatment regimen and duration should follow adult guidelines (see Dosage; Adult).
Patients with Hepatic Impairment
Dose modifications due to hepatic impairment are not required for ledipasvir with sofosbuvir.
When used in patients with decompensated cirrhosis, dose modifications are recommended for ribavirin. Modifications are based on the medicinal product that ribavirin is combined with. Consult the product information for ledipasvir with sofosbuvir for recommended modifications of ribavirin in this patient group.
Additional Dosage Information
Missed dose
If a dose is missed within 18 hours of the normal time of taking, the patient should take the missed dose as soon as possible, and resume their normal dose regimen. If a dose is missed after 18 hours then the patient should wait and take the next dose at the usual time. The patient should not take a double dose.
If vomiting occurs within 5 hours of dosing, an additional dose should be taken. If vomiting occurs more than 5 hours after taking, no further dose is needed.
Administration
Tablets
Patients that weigh less than 17kg are not recommended to take tablets.
Oral granules formulation
Ledipasvir with sofosbuvir granules can be taken with or without food. Patients should be instructed that the granules can be taken directly into the mouth and swallowed. Patients should be instructed to swallow the entire contents without chewing. To help with swallowing the patient may use food or water.
Taking with food.
Patients should be instructed to sprinkle the granules on one or more spoonfuls of non-acidic soft food (chocolate syrup, mashed potato, ice cream) at or below room temperature. Patients should be instructed to take the granules within 30 minutes of mixing with food and to swallow the entire contents without chewing to avoid a bitter taste.
Taking with water.
Patients should be instructed that the granules can be taken directly into the mouth and swallowed with water.
Contraindications
Children under 3 years
Breastfeeding
Galactosaemia
Pregnancy
Precautions and Warnings
Decompensated liver disease
Diabetes mellitus
End stage renal disease
Glucose-galactose malabsorption syndrome
Hepatitis B
Lactose intolerance
Renal impairment - eGFR below 30ml/minute/1.73m sq
Monitor HBV levels during and after treatment in patients with co-infection
Before initiating screen all patients for hepatitis B infection
Not all formulations are suitable for all age groups/body weights
Treatment should be started by a doctor experienced in hepatitis management
Contains lactose
Contains sunset yellow (E110) - may cause allergic reaction
Advise patient on concurrent use of proton pump inhibitors
Diabetic control may need adjustment
Monitor blood glucose closely in patients with diabetes mellitus
Reactivation of hepatitis B may occur in chronic carriers
Advise patient not to take St John's wort concurrently
Avoid antacids within 4 hours of dose
Advise patients with diabetes of the increased risk of hypoglycaemia
Take another dose if vomiting occurs within 5 hours
There are no data to support re-treatment with a subsequent regime that contains a NS5A inhibitor in patients where treatment with ledipasvir with sofosbuvir has failed. Similarly, patients who have failed therapy with a NS3/4A protease inhibitor, there are no data to support re-treatment with NS3/4A protease inhibitors. In this instance, such patients may therefore be dependant on other drug classes for clearance of hepatitis C virus infection. Consideration should be given to longer treatment for patients with uncertain subsequent re-treatment options.
Patients with diabetes may experience improved glucose control and symptomatic hypoglycaemia following treatment initiation. Monitor blood glucose levels closely, particularly within the first 3 months, and adjust diabetic medication as necessary. Inform specialist in charge of diabetic care of treatment initiation.
Pregnancy and Lactation
Pregnancy
Ledipasvir with sofosbuvir is contraindicated during pregnancy.
The manufacturer suggests as a precautionary measure, it is preferable to avoid the use of ledipasvir with sofosbuvir during pregnancy. At the time of writing, there are limited data from the use of ledipasvir or sofosbuvir during pregnancy.
Animal studies have shown no effects on foetal development. However, it had not been possible to achieve equivalent sofosbuvir levels in rats relative to the clinical dose in humans.
Concurrent therapies should be considered.
Lactation
Ledipasvir with sofosbuvir is contraindicated during breastfeeding.
The manufacturer does not recommend the use of ledipasvir with sofosbuvir during breastfeeding, as the risk to the infant cannot be excluded. It is unknown if ledipasvir and sofosbuvir is excreted into breast milk. Effects on exposed infants are unknown.
LactMed (2021) indicates that if ledipasvir alone or in combination with sofosbuvir is required by the mother, it is not a reason to stop breastfeeding. Some sources recommend against breastfeeding if this drug combination is used with ribavirin.
Side Effects
Angioedema
Bradycardia
Decrease in haemoglobin
Fatigue
Headache
Heart block
Rash
Stevens-Johnson syndrome
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2020
Reference Sources
Summary of Product Characteristics: Harvoni 33.75mg/150mg coated granules in sachet. Gilead Sciences Ltd. Revised October 2021.
Summary of Product Characteristics: Harvoni 45mg/200mg coated granules in sachet. Gilead Sciences Ltd. Revised October 2021.
Summary of Product Characteristics: Harvoni 45mg/200mg film-coated tablets. Gilead Sciences Ltd. Revised January 2021.
Summary of Product Characteristics: Harvoni 90mg/400mg film-coated tablets. Gilead Sciences Ltd. Revised January 2021.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Ledipasvir Last revised: 19 July 2021
Last accessed: 17 December 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Sofosbuvir Last revised: 19 July 2021
Last accessed: 17 December 2021
PRAC warns of risk of hepatitis B re-activation with direct-acting antivirals for hepatitis C. Available at: https://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2016/12/WC500217496.pdf
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