Daclavir Dosage/Direction for Use

Treatment with Daclavir should be initiated and monitored by a physician experienced in the management of chronic hepatitis C.
Posology: The recommended dose of Daclavir is 60 mg once daily, to be taken orally with or without meals.
Daclavir must be administered in combination with other medicinal products. The Product Information for the other medicinal products in the regimen should also be consulted before initiation of therapy with Daclavir.
Table 10 provides the recommended Daclavir-containing treatment regimens and duration based on HCV genotype and patient population. For specific dosage recommendations for sofosbuvir, refer to the prescribing information. The optimal duration of Daclavir and sofosbuvir with or without ribavirin has not been established for HCV genotype 3 patients with cirrhosis of for HCV genotype 1 patients with Child-Pugh C cirrhosis (see Pharmacology: Pharmacodynamics under Actions). (See Table 10.)

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Daclavir + peginterferon alfa + ribavirin: The recommended regimen for patients with genotype 4 infection, without cirrhosis or with compensated cirrhosis is Daclavir given for 24 weeks, in combination with 24-48 weeks of peginterferon alfa and ribavirin: If HCV RNA is undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks.
If undetectable HCV RNA is achieved, but not at both treatment weeks 4 and 12, Daclavir should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
Ribavirin Dosing Guidelines: The dose of ribavirin, when combined with Daclavir, is weight-based (1,000 or 1,200 mg in patients <75 kg or ≥75 kg, respectively). Refer to the Product Information of ribavirin.
For patients with Child-Pugh A, B, or C cirrhosis or recurrence of HCV infection after liver transplantation, the recommended initial dose of ribavirin is 600 mg daily with food. If the starting dose is well-tolerated, the dose can be titrated up to a maximum of 1,000-1,200 mg daily (breakpoint 75 kg). If the starting dose is not well-tolerated, the dose should be reduced as clinically indicated, based on haemoglobin and creatinine clearance measurements (see Table 11).

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Dose modification, interruption and discontinuation: Dose modification of Daclavir to manage adverse reactions is not recommended. If treatment interruption of components in the regimen is necessary because of adverse reactions, Daclavir must not be given as monotherapy.
There are no virologic treatment stopping rules that apply to the combination of Daclavir with sofosbuvir.
Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with Daclavir, peginterferon alfa and ribavirin: It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR); therefore discontinuation of treatment is recommended in these patients. The HCV RNA thresholds that trigger discontinuation of treatment (i.e. treatment stopping rules) are presented in Table 12. (See Table 12.)

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Dose recommendation for concomitant medicines: Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4): The dose of Daclavir should be reduced to 30 mg once daily when coadministered with strong inhibitors of CYP3A4.
Moderate inducers of CYP3A4: The dose of Daclavir should be increased to 90 mg once daily when coadministered with moderate inducers of CYP3A4. See Interactions.
Missed doses: Patients should be instructed that, if patients miss a dose of Daclavir, the dose should be taken as soon as possible if remembered within 20 hours of the scheduled dose time. However, if the missed dose is remembered more than 20 hours after the scheduled dose, the dose should be skipped and the next dose taken at the appropriate time.
Special populations: Elderly: No dose adjustment of Daclavir is required for patients aged ≥65 years (see Pharmacology: Pharmacokinetics under Actions).
Renal impairment: No dose adjustment of Daclavir is required for patients with any degree of renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No dose adjustment of Daclavir is required for patients with mild (Child-Pugh A, score 5-6), moderate (Child-Pugh B, score 7-9) or severe (Child-Pugh C, score ≥10) hepatic impairment (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Daclavir in children and adolescents aged below 18 years have not yet been established. No data are available.
Method of administration: Daclavir is to be taken orally with or without meals. Patients should be instructed to swallow the tablet whole. The film-coated tablet should not be chewed or crushed due to the unpleasant taste of the active substance.