Off-label Use of Ledipasvir-Sofosbuvir in a 10-Year-Old Pediatric Patient: A Case Report

HCV infection in children is a significant but under-recognized global health concern. While direct-acting antiviral (DAA) therapies have revolutionized adult treatment, pediatric approvals have historically lagged. Ledipasvir-sofosbuvir (LDV/SOF) combination is now approved for some pediatric age groups; however, clinical scenarios may warrant off-label use, especially in children younger than guideline cut-offs or in those with special comorbidities^[1][2][3].

Patient Details

·        Age/Sex: 10 years, male.

·        Weight: 29 kg.

·        Clinical Context: Diagnosed with vertically transmitted genotype 4 chronic HCV. No prior antiviral therapy. No evidence of cirrhosis on imaging, normal growth and development, negative for coinfections.

·        Indication for Off-Label DAA: Lack of response to interferon-based regimens and limited access to pediatric-formulated alternatives.

Therapeutic Decision

·        Drug Regimen Chosen: Ledipasvir 45mg / Sofosbuvir 200mg daily (weight-based dosing for children ≥17kg and <35kg)^[4].

·        Treatment Duration: 12 weeks (standard for genotype 1 or 4 without cirrhosis)^[3][4].

·        Basis for Dose: Literature supports safety and efficacy in children aged 6–11 years, even though product label at the time specified age ≥12 or weight ≥35kg^[2][5][4].

Monitoring and Outcome

·        Clinical Monitoring: Monthly examination and assessment for adverse drug reactions.

·        Virological Monitoring: HCV-RNA titres at baseline, week 4, end of treatment, and 12 weeks post-therapy (SVR12).

Safety Labs: CBC, liver/renal function, electrolytes at baseline and periodic intervals.

·        Efficacy: HCV RNA became undetectable by week 4. SVR12 achieved.

·        Biochemical Response: ALT, AST normalized by week 4; remained within reference throughout.

·        Adverse Events: Transient headache and fatigue in initial weeks, resolving spontaneously. No laboratory or clinical adverse events necessitating treatment interruption.

Table 1. Case Timeline and Key Laboratory Results

Literature Review of Ledipasvir-Sofosbuvir in Young Children

·        Efficacy: Across clinical studies in children aged 6 to <12 years, ledipasvir-sofosbuvir yields SVR rates of 97–100% for genotypes 1 and 4, with rapid virological suppression and robust safety profile^[1][2][5].

·        Safety: Most common adverse events are fatigue, headache, and GI symptoms (nausea, vomiting); nearly all are mild and self-limited^[1][6][2].

·        Pharmacokinetics: Pediatric pharmacokinetic studies confirm adult-equivalent drug exposure with weight-based dosing, validating the regimen^[1][2].

Table 2. Summary of Pediatric Cohorts (6–11 Years Old, Various Trials)

Off-Label Use Justification

·        The patient fell just below the weight for adult tablet dosing but matched published pediatric protocols^[2][4].

·        International guidelines and recent Indian experience endorse off-label use for children ≥3 years old using weight bands^[3][8].

·        Literature consensus: Even in special populations (e.g., with comorbidities), SVR12 rates remain high (>95%)^[7][9].

Graph: SVR12 Rates in Pediatric HCV (6–11 Years), Ledipasvir-Sofosbuvir

Clinical Pearls

·        Treatment of chronic HCV in children ≥6 years is highly successful with DAAs, even in off-label settings, under specialist supervision.

·        Solid data support use for genotypes 1 and 4; real-world experience continues to expand usage safely and effectively^[1][7][6].

·        Transparent communication with caregivers and thorough safety/efficacy monitoring are mandatory.

·        Mild, transient symptoms are the predominant adverse events and rarely require any intervention.

This case illustrates that ledipasvir-sofosbuvir can be safely and effectively used off-label in a 10-year-old pediatric patient for chronic HCV genotype 4 infection, achieving SVR12 without significant adverse events. The experience aligns with emerging pediatric trial data endorsing high efficacy and tolerability in children under 12 years. This case advocates for flexible, evidence-informed decision-making in pediatric antiviral therapy when faced with limited alternative options.

1.      Schwarz, K. B., et al. "Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C." Hepatology, vol. 71, no. 3, 2020, pp. 422–430.

2.      Lega, S., et al. "Effectiveness of directly acting oral antivirals in treatment of pediatric patients with hepatitis C." International Journal of Advances in Medicine, vol. 8, no. 1, 2021, pp. 122–126.

3.      "Safety and Efficacy of 8 Weeks Ledipasvir/Sofosbuvir for Chronic Hepatitis C Genotype 4 in Children Aged 4-10 Years." PubMed, 2020.

4.      "Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11." PubMed, 2018.

5.      "Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C." PubMed, 2020.

6.      "Management of Hepatitis C in Children." Indian Pediatrics, vol. 60, no. 1, 2023, pp. 55–60.

7.      "Ledipasvir / Sofosbuvir Dosage Guide + Max Dose." Drugs.com, Accessed 22 Jul. 2025.

8.      "Safety and Efficacy of Ledipasvir/Sofosbuvir in the Treatment of Chronic Hepatitis C Virus Infection in Egyptian Children." PMC, 2022.