Brand Name: Daclavirocyrl 60 mg Tablet
Active Ingredient: Daclatasvir
When is Daclavirocyrl tablet prescribed for?
Daclavirocyrl is indicated in combination with other medicinal products for the treatment of chronic hepatitis C virus (HCV) infection in adults.
For HCV genotype specific activity, see Insert leaflet.
How should you take Daclavirocyrl tablet?
Treatment with Daclavirocyrl should be initiated and monitored by a physician experienced in the management of chronic hepatitis C.
The recommended dose of Daclavirocyrl is 60mg once daily, to be taken orally with or without meals. Daclavirocyrl must be administered in combination with other medicinal products.
The Summary of Product Characteristics for the other medicinal products in the regimen should also be consulted before initiation of therapy with Daclavirocyrl.
When you should not take Daclavirocyrl tablet?
- Hypersensitivity to the active substance or to any of the excipients.
- Coadministration with medicinal products that strongly induce cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transporter (P-gp) and thus may lead to lower exposure and loss of efficacy of Daclavirocyrl. These active substances include but are not limited to phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St John's wort (Hypericum perforatum).
Special warning and precautions on using Daclavirocyrl tablet:
Daclavirocyrl must not be administered as monotherapy. Daclavirocyrl must be administered in combination with other medicinal products for the treatment of chronic HCV infection.
Severe bradycardia and heart block
Cases of severe bradycardia and heart block have been observed when Daclavirocyrl is used in combination with sofosbuvir and concomitant amiodarone with or without other drugs that lower heart rate.
The mechanism is not established.
The concomitant use of amiodarone was limited through the clinical development of sofosbuvir plus direct-acting antivirals (DAAs). Cases are potentially life threatening, therefore amiodarone should only be used in patients on Daclavirocyrl and sofosbuvir when other alternative antiarrhythmic treatments are not tolerated or are contraindicated.
Should concomitant use of amiodarone be considered necessary it is recommended that patients are closely monitored when initiating Daclavirocyrl in combination with sofosbuvir.
Patients who are identified as being at high risk of bradyarrhythmia should be continuously monitored for 48 hours in an appropriate clinical setting.
Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated on Daclavirocyrl in combination with sofosbuvir.
All patients receiving Daclavirocyrl and sofosbuvir in combination with amiodarone with or without other drugs that lower heart rate should also be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.
Concerning recommended regimens with different HCV genotypes and genotype-specific virological and clinical activity, see insert leaflet
Decompensated liver disease
The safety and efficacy of Daclavirocyrl in the treatment of HCV infection in patients with decompensated liver disease have not been established.
Retreatment with daclatasvir
The efficacy of Daclavirocyrl as part of a retreatment regimen in patients with prior exposure to a NS5A inhibitor has not been established.
Pregnancy and contraception requirements
Daclavirocyrl should not be used during pregnancy or in women of childbearing potential not using contraception.
When Daclavirocyrl is used in combination with ribavirin, the contraindications and warnings for that medicinal product are applicable. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin; therefore, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients (see the Summary of Product Characteristics for ribavirin).
Organ transplant patients
The safety and efficacy of Daclavirocyrl in the treatment of HCV infection in patients who are pre-, peri-, or post-liver transplant or other organ transplant patients have not been established.
HCV/HIV (human immunodeficiency virus) co-infection
The safety and efficacy of Daclavirocyrl in the treatment of HCV infection in patients who are co-infected with HIV have not been established.
HCV/HBV (hepatitis B virus) co-infection
The safety and efficacy of Daclavirocyrl in the treatment of HCV infection in patients who are co-infected with HBV have not been investigated.
Clinical data in patients aged ≥65 years are limited. In clinical studies of Daclavirocyrl in combination with sofosbuvir or with peginterferon alfa and ribavirin, no differences in responses were observed between elderly and younger patients.
Daclavirocyrl is not recommended for use in children and adolescents aged below 18 years because the safety and efficacy have not been established in this population.
Important information about some of the ingredients in Daclavirocyrl
Daclavirocyrl contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Possible Drug interaction with Daclavirocyrl tablet:
Contraindications of concomitant use
Daclavirocyrl is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St John's wort (Hypericum perforatum), and thus may lead to lower exposure and loss of efficacy of Daclavirocyrl.
Potential for interaction with other medicinal products
Daclatasvir is a substrate of CYP3A4 and P-gp. Strong or moderate inducers of CYP3A4 and P-gp may decrease the plasma levels and therapeutic effect of daclatasvir. Coadministration with strong inducers of CYP3A4 and P-gp is contraindicated while dose adjustment of Daclavirocyrl is recommended when coadministered with moderate inducers of CYP3A4 and P-gp.
Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of Daclavirocyrl is recommended when coadministered with strong inhibitors of CYP3A4. Coadministration of medicines that inhibit P-gp activity is likely to a have limited effect on daclatasvir exposure.
Daclatasvir is an inhibitor of P-gp, organic anion transporting polypeptide (OATP) 1B1, organic cation transporter (OCT)1 and breast cancer resistance protein (BCRP). Administration of Daclavirocyrl may increase systemic exposure to medicinal products that are substrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong their therapeutic effect and adverse reactions. Caution should be used if the medicinal product has a narrow therapeutic range.
Daclatasvir is a very weak inducer of CYP3A4 and caused a 13% decrease in midazolam exposure. However, as this is a limited effect, dose adjustment of concomitantly administered CYP3A4 substrates is not necessary.
Refer to the respective Summary of Product Characteristics for drug interaction information for other medicinal products in the regimen.
Special information if you are pregnant or breastfeeding
There are no data from the use of daclatasvir in pregnant women.
Studies of daclatasvir in animals have shown embryotoxic and teratogenic effects. The potential risk for humans is unknown.
Daclavirocyrl should not be used during pregnancy or in women of childbearing potential not using contraception. Use of highly effective contraception should be continued for 5 weeks after completion of Daclavirocyrl therapy. Since Daclavirocyrl is used in combination with other agents, the contraindications and warnings for those medicinal products are applicable.
For detailed recommendations regarding pregnancy and contraception, refer to the Summary of Product Characteristics for ribavirin and peginterferon alfa.
It is not known whether daclatasvir is excreted in human milk. Available pharmacokinetic and toxicological data in animals have shown excretion of daclatasvir and metabolites in milk. A risk to the newborn/infant cannot be excluded. Mothers should be instructed not to breastfeed if they are taking Daclavirocyrl.
Possible Side effects of Daclavirocyrl tablet
- Daclavirocyrl in combination with sofosbuvir
The most frequently reported adverse reactions were fatigue, headache, and nausea. No Grade 3 or 4 adverse reactions were reported.
Two patients discontinued for adverse events, which were considered unrelated to study therapy.
- Daclavirocyrl in combination with peginterferon alfa and ribavirin
The most frequently reported adverse reactions were fatigue, headache, pruritus, insomnia, influenza-like illness, dry skin, nausea, decreased appetite, alopecia, rash, asthenia, irritability, myalgia, anaemia, pyrexia, cough, dyspnoea, neutropenia, diarrhoea and arthralgia. The most frequently reported adverse reactions of at least Grade 3 severity (frequency of 1% or greater) were neutropenia, anaemia and lymphopenia. The safety profile of daclatasvir in combination with peginterferon alfa and ribavirin was similar to that seen with peginterferon alfa and ribavirin alone, including among patients with cirrhosis.
For more information about the undesirable effects, see insert leaflet.