Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

WHOPAR Part 4

December 2023

WHO-PQ RECOMMENDED
SUMMARY OF PRODUCT CHARACTERISTICS

This summary of product characteristics focuses on uses of the medicine covered by WHO’s Prequalification
Team - Medicines. The recommendations for use are based on WHO guidelines and on information fromstringent regulatory authorities.*
The medicine may be authorised for additional or different uses by national medicines regulatory
authorities.

*

https://extranet.who.int/prequal/sites/default/files/document_files/75%20SRA%20clarification_Feb2017_newtempl.pdf

Page 1 of 21

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

1.

WHOPAR Part 4

December 2023

NAME OF THE MEDICINAL PRODUCT[HP016 trade name]†

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Film coated tablet contains 60 mg daclatasvir (as dihydrochloride)
Excipients with potential clinical effect
Each tablet contains 116 mg anhydrous lactose
For a full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Film-coated tablets.
Green, capsule-shaped film-coated tablets. They are biconvex (rounded on top and bottom) with a bevelededge. The tablets have a break line on each side; one side has ‘D’ debossed (stamped into the tablet) to theleft of the break line and ‘T’ debossed (stamped into the tablet) to the right of the line. The other side has ‘6’
debossed (stamped into the tablet) on the left of the line and ‘0’ debossed (stamped into the tablet) on theright of the line.
The break line can be used to divide [HP016 trade name] into equal doses.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications[HP016 trade name] is indicated in combination with sofosbuvir for the treatment of chronic hepatitis C virus(HCV) infection in adults and children.
Treatment regimens should follow the most recent WHO treatment guidelines, supplemented by otherauthoritative guidelines.
4.2

Posology and method of administration

Treatment with [HP016 trade name] should be initiated and monitored by a health care provider experienced
in the management of chronic hepatitis C.
Posology[HP016 trade name] must be given together with sofosbuvir.
[HP016 trade name] is taken once a day by mouth, and the recommended dose depends on body weight, as
follows:
Body weight

Regimen and duration*

Daily dose of daclatasvir

All genotypes
14 kg to less than 26 kg

use alternative formulation

30 mg

26 kg or more
1 tablet per day for 12 weeks
60 mg* Treatment for 24 weeks is recommended in those who are treatment experienced or who have compensated cirrhosis.
It may also be considered in settings where genotype 3 is known to be highly prevalent (>10%).

[HP016 trade name] can be used in patients co-infected with human immunodeficiency virus (HIV).
†

Trade names are not prequalified by WHO. This is the national medicines regulatory agency’s responsibility.
Page 2 of 21

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

WHOPAR Part 4

December 2023

Dose recommendation for concomitant medicines
Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4)
An alternative product allowing administration of half the dose of daclatasvir (e.g. 30 mg once daily forpatients weighing 26 kg or more) should be used if co-administration with strong inhibitors of CYP3A4 isnecessary.
Moderate inducers of CYP3A4
An alternative product allowing administration of a higher dose daclatasvir (e.g. 90 mg once daily forpatients weighing 26 kg or more) should be used if co-administration with moderate inducers of CYP3A4 isnecessary.
Missed doses
Patients should be instructed that, if they miss a dose of [HP016 trade name], the dose should be taken assoon as possible if remembered within 20 hours of the scheduled dose time. However, if the missed dose isremembered more than 20 hours after the scheduled dose, the dose should be skipped, and the next dosetaken at the appropriate time.
Special populations
Elderly
No dose adjustment of [HP016 trade name] is required for patients aged ≥65 years (see section 5.2).
Renal impairment
No dose adjustment of [HP016 trade name] is required for patients with any degree of renal impairment (seesection 5.2).
Hepatic impairment
No dose adjustment of [HP016 trade name] is required for patients with any degree of hepatic impairment(see sections 4.4 and 5.2).
Method of administration[HP016 trade name] is to be taken orally with or without food. Patients should be instructed to swallow thetablet whole. The tablet should not be chewed or crushed due the unpleasant taste of the active substance.
4.3

Contraindications[HP016 trade name] should not be given to patients with hypersensitivity to the active substance or to any ofthe excipients listed in section 6.1.
[HP016 trade name] should not be co-administered with medicinal products that strongly induce cytochrome
P450 3A4 (CYP3A4) and/or P-glycoprotein transporter (P-gp) as these substances may lead to lower
exposure and loss of efficacy of [HP016 trade name]. These active substances include but are not limited tophenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic
dexamethasone, and the herbal product St John’s wort (Hypericum perforatum).
4.4

Special warnings and precautions for use[HP016 trade name] must be given with sofosbuvir (see sections 4.1 and 4.2).
Severe bradycardia and heart block
Cases of severe bradycardia and heart block have been observed when daclatasvir 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 directacting antivirals (DAAs). Cases are potentially life threatening, therefore amiodarone should only be used inPage 3 of 21

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

WHOPAR Part 4

December 2023

patients on daclatasvir and sofosbuvir when other alternative antiarrhythmic treatments are not tolerated orare contraindicated. Should concomitant use of amiodarone be considered necessary it is recommended thatpatients are closely monitored when initiating daclatasvir 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 daclatasvir in
combination with sofosbuvir.
All patients receiving daclatasvir and sofosbuvir in combination with amiodarone with or without otherdrugs 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.
HCV/HBV (hepatitis B virus) co-infection
Cases of hepatitis B virus (HBV) reactivation, some of them fatal, have been reported during or after
treatment with direct-acting antiviral agents. HBV screening should be performed in all patients before
initiation of treatment. HBV/HCV co-infected patients are at risk of HBV reactivation, and should therefore
be monitored and managed according to current clinical guidelines.
Retreatment with daclatasvir
The efficacy of [HP016 trade name] as part of a retreatment regimen in patients with prior exposure to a
NS5A inhibitor has not been established.
Pregnancy and contraception requirements[HP016 trade name] 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[HP016 trade name] therapy (see section 4.6).
Interactions with medicinal products[HP016 trade name] can alter the concentration of other medicinal products if given at the same time, andother medicinal products may alter the concentration of daclatasvir. See section 4.3 and section 4.5 forfurther information.
Use in patients with diabetes
Patients with diabetes may experience improved glucose control, potentially resulting in symptomatic
hypoglycaemia, after beginning HCV DAA treatment. Glucose levels of diabetic patients starting DAA
therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication
modified when necessary. The health care provider in charge of the diabetic care of the patient should be
informed when DAA therapy is started.
Excipients[HP016 trade name] contains lactose. Lactose is a source of glucose and galactose. The small amount oflactose in each dose is unlikely to cause symptoms of lactose intolerance in other patients. If, however, youhave one of the rare genetic disorders galactosaemia, glucose-galactose intolerance or congenital lactase
deficiency you must talk to your health care provider before taking this medicine.
It is important to consider the contribution of excipients from all the medicines that the patient is taking.
4.5

Interaction with other medicinal products and other forms of interaction

Potential for interaction with other medicinal products
Daclatasvir is a substrate of CYP3A4, P-gp and organic cation transporter (OCT) 1 and an inhibitor of P-gp,
organic anion transporting polypeptide (OATP) 1B1, OCT1 and breast cancer resistance protein (BCRP).

Page 4 of 21

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

WHOPAR Part 4

December 2023

Effects on daclatasvir
Strong or moderate inducers of CYP3A4 and P-gp may decrease the plasma levels and therapeutic effect of[HP016 trade name]. Co-administration with strong inducers of CYP3A4 and P-gp is contraindicated (seesection 4.3), while dose adjustment of [HP016 trade name] is recommended when co-administered withmoderate inducers of CYP3A4 and P-gp (see table below).
Strong inhibitors of CYP3A4 may increase the plasma levels of [HP016 trade name]. Dose adjustment of[HP016 trade name] is recommended when co-administered with strong inhibitors of CYP3A4 (see tablebelow).
Co-administration of medicines that inhibit P-gp or OCT1 activity is likely to have a limited effect on
daclatasvir exposure.
Effects on co-administered drugs
Administration of [HP016 trade name] may increase systemic exposure to medicinal products that aresubstrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong their therapeutic effect andadverse reactions. Caution should be used if the medicinal product has a narrow therapeutic range (see tablebelow).
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 othermedicinal products in the regimen.
Patients treated with vitamin K antagonists
As liver function may change during treatment with [HP016 trade name], a close monitoring of International
Normalized Ratio (INR) values is recommended.
Tabulated summary of interactions
The table below provides information from drug interaction studies with daclatasvir including clinicalrecommendations for established or potentially significant drug interactions. Clinically relevant increase inconcentration is indicated as “↑”, clinically relevant decrease as “↓”, no clinically relevant change as “↔”.
If available, ratios of geometric means are shown, with 90% confidence intervals (CI) in parentheses. The
studies presented in the table were conducted in healthy adult subjects unless otherwise noted. The table is
not all-inclusive.
Interactions and dose recommendations with other medicinal products
Medicinal products by
Recommendations concerning
Interaction
therapeutic areas
co-administration
ANTIVIRALS, HCV
Nucleotide analogue polymerase inhibitor
No dose adjustment of [HP016
Sofosbuvir 400 mg once daily↔ Daclatasvir*
trade name] or sofosbuvir is(daclatasvir 60 mg once daily)
AUC: 0.95 (0.82, 1.10)
required.
Cmax: 0.88 (0.78, 0.99)
Study conducted in patients with
Cmin: 0.91 (0.71, 1.16)
chronic HCV infection↔ GS-331007 (major
metabolite of sofosbuvir)
AUC: 1.0 (0.95, 1.08)
Cmax: 0.8 (0.77, 0.90)
Cmin: 1.4 (1.35, 1.53)

Page 5 of 21

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

WHOPAR Part 4

December 2023

Medicinal products by
therapeutic areas
Other HCV antivirals

Interaction

Recommendations concerning
co-administration

Peginterferon alfa 180 μg once
weekly and ribavirin 1000 mg
or 1200 mg/day in two divided
doses(daclatasvir 60 mg once daily)↔ Daclatasvir

No dose adjustment of [HP016
trade name], peginterferon alfa, or
ribavirin is required.

Study conducted in patients withchronic HCV infection

AUC: ↔*
Cmax: ↔*
Cmin: ↔*
↔ Peginterferon alfa
Cmin: ↔*↔ Ribavirin
AUC: 0.94 (0.80, 1.11)
Cmax: 0.94 (0.79, 1.11)
Cmin: 0.98 (0.82, 1.17)

ANTIVIRALS, HIV or HBVProtease inhibitors (PIs)
Atazanavir 300 mg/ritonavir
100 mg once daily

Atazanavir/cobicistat↑ Daclatasvir
AUC*: 2.10 (1.95, 2.26)
Cmax*: 1.35 (1.24, 1.47)
Cmin*: 3.65 (3.25, 4.11)
CYP3A4 inhibition byritonavir*results are dose-normalised
to 60 mg dose.
Interaction not studied.
Expected due to CYP3A4
inhibition byatazanavir/cobicistat:

The dose of daclatasvir should be
reduced when co-administeredwith atazanavir/ritonavir,
atazanavir/cobicistat or otherstrong inhibitors of CYP3A4 (seesection 4.2).

↑ Daclatasvir
Darunavir 800 mg/ritonavir
100 mg once daily(daclatasvir 30 mg once daily)

Darunavir/cobicistat↑ Daclatasvir
AUC: 1.41 (1.32, 1.50)
Cmax: 0.77 (0.70, 0.85)↔ Darunavir
AUC: 0.90 (0.73, 1.11)
Cmax: 0.97 (0.80, 1.17)
Cmin: 0.98 (0.67, 1.44)
Interaction not studied.
Expected:

The dose of daclatasvir should be
reduced when co-administeredwith darunavir/ritonavir, or otherstrong inhibitors of CYP3A4 (seesection 4.2). However, no dose
reduction is envisaged when
given with darunavir/cobicistat.
No dose adjustment of
darunavir/ritonavir or
darunavir/cobicistat is required.

↔ Daclatasvir
Lopinavir 400 mg/ritonavir 100
mg twice daily(daclatasvir 30 mg once daily)↔ Daclatasvir
AUC: 1.15 (1.07, 1.24)
Cmax: 0.67 (0.61, 0.74)↔ Lopinavir
AUC: 1.15 (0.77, 1.72)
Page 6 of 21

The dose of daclatasvir should be
reduced when co-administeredwith lopinavir/ritonavir, or otherstrong inhibitors of CYP3A4 (seesection 4.2). No dose adjustmentof lopinavir/ritonavir is required.

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas

WHOPAR Part 4

December 2023

Recommendations concerning
co-administration

Interaction

Cmax: 1.22 (1.06, 1.41)
Cmin: 1.54 (0.46, 5.07)
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
Tenofovir disoproxil 245 mg↔ Daclatasvir
once daily
AUC: 1.10 (1.01, 1.21)(daclatasvir 60 mg once daily)
Cmax: 1.06 (0.98, 1.15)
Cmin: 1.15 (1.02, 1.30)↔ Tenofovir
AUC: 1.10 (1.05, 1.15)
Cmax: 0.95 (0.89, 1.02)
Cmin: 1.17 (1.10, 1.24)
Interaction not studied.
Expected:

Lamivudine
Zidovudine
Emtricitabine↔ Daclatasvir
Abacavir↔ NRTI
Didanosine
Stavudine
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz 600 mg once daily↓ Daclatasvir(daclatasvir 60 mg once daily/)
AUC*: 0.68 (0.60, 0.78)
Cmax*: 0.83 (0.76, 0.92)
Cmin*: 0.41 (0.34, 0.50)
Moderate induction of
CYP3A4 by efavirenz*results are dose-normalised to

No dose adjustment of [HP016
trade name] or tenofovir
disoproxil is required.

No dose adjustment of [HP016
trade name] or the NRTI isrequired.

The dose of daclatasvir should be
increased when co-administeredwith efavirenz (see section 4.2).

60 mg dose.

Etravirine
Nevirapine

Rilpivirine↓ Daclatasvir
Moderate induction of
CYP3A4 by etravirine or
nevirapine
Interaction not studied.
Expected:↔ Daclatasvir

The dose of daclatasvir should be
increased when co-administeredwith etravirine or nevirapine (seesection 4.2).
No dose adjustment of [HP016
trade name] or rilpivirine isrequired.

↔ Rilpivirine
Integrase inhibitors
Dolutegravir 50 mg once daily(daclatasvir 60 mg once daily)↔ Daclatasvir
AUC: 0.98 (0.83, 1.15)
Cmax: 1.03 (0.84, 1.25)
Cmin: 1.06 (0.88, 1.29)↑ Dolutegravir
AUC: 1.33 (1.11, 1.59)
Cmax: 1.29 (1.07, 1.57)
Cmin: 1.45 (1.25, 1.68)
Inhibition of P-gp and BCRP
Page 7 of 21

No dose adjustment of [HP016
trade name] or dolutegravir isrequired.

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas
Raltegravir

WHOPAR Part 4

December 2023

Recommendations concerning
co-administration

Interaction
by daclatasvir.
Interaction not studied.
Expected:↔ Daclatasvir

No dose adjustment of [HP016
trade name] or raltegravir isrequired.

↔ Raltegravir
Elvitegravir, cobicistat,emtricitabine, tenofovir
disoproxil
Other cobicistat-containing
regimens (except
darunavir/cobicistat, see above)
Fusion inhibitor
Enfuvirtide↑ Daclatasvir
CYP3A4 inhibition bycobicistat

The dose of daclatasvir should be
reduced when co-administeredwith cobicistat or other strong
inhibitors of CYP3A4 (seesection 4.2)

Interaction not studied.
Expected:

No dose adjustment of [HP016
trade name] or enfuvirtide isrequired.

↔ Daclatasvir↔ Enfuvirtide
ACID REDUCING AGENTS
H2-receptor antagonists
Famotidine 40 mg single dose
(daclatasvir 60 mg single dose)

Proton pump inhibitors
Omeprazole 40 mg once daily(daclatasvir 60 mg single dose)

ANTIBACTERIALSClarithromycin
Telithromycin↔ Daclatasvir
AUC: 0.82 (0.70, 0.96)
Cmax: 0.56 (0.46, 0.67)
Cmin: 0.89 (0.75, 1.06)
Increase in gastric pH

No dose adjustment of [HP016
trade name] is required.

↔ Daclatasvir
AUC: 0.84 (0.73, 0.96)
Cmax: 0.64 (0.54, 0.77)
Cmin: 0.92 (0.80, 1.05)
Increase in gastric pH

No dose adjustment of [HP016
trade name] is required.

Interaction not studied.
Expected due to CYP3A4
inhibition by the
antibacterial:

The dose of daclatasvir should be
reduced when co-administeredwith clarithromycin,
telithromycin or other strong
inhibitors of CYP3A4 (seesection 4.2).
Administration of [HP016 tradename] with erythromycin may
result in increased concentrationsof daclatasvir. Caution is advised.

↑ Daclatasvir
Erythromycin

Interaction not studied.
Expected due to CYP3A4
inhibition by the
antibacterial:↑ Daclatasvir

Azithromycin
Ciprofloxacin

Interaction not studied.
Expected:
Page 8 of 21

No dose adjustment of [HP016
trade name] or azithromycin orDaclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas

WHOPAR Part 4Interaction↔ Daclatasvir

December 2023

Recommendations concerning
co-administration
ciprofloxacin is required.

↔ Azithromycin or
Ciprofloxacin
ANTICOAGULANTS
Dabigatran etexilate

Interaction not studied.
Expected due to inhibition of
P-gp by daclatasvir:↑ Dabigatran etexilate

Warfarin or other vitamin K
antagonists

Interaction not studied.
Expected:↔ Daclatasvir↔ Warfarin

ANTICONVULSANTS
Carbamazepine
Oxcarbazepine
Phenobarbital
Phenytoin

Interaction not studied.
Expected due to CYP3A4
induction by the
anticonvulsant:↓ Daclatasvir

ANTIDEPRESSANTS
Selective serotonin reuptake inhibitors
Escitalopram 10 mg once daily↔ Daclatasvir(daclatasvir 60 mg once daily)
AUC: 1.12 (1.01, 1.26)
Cmax: 1.14 (0.98, 1.32)
Cmin: 1.23 (1.09, 1.38)

Safety monitoring is advisedwhen initiating treatment with
[HP016 trade name] in patients
receiving dabigatran etexilate orother intestinal P-gp substrates
that have a narrow therapeutic
range.
No dose adjustment of [HP016
trade name] or warfarin isrequired. Close monitoring of
INR values is recommended withall vitamin K antagonists. This isdue to liver function that may
change during treatment with
[HP016 trade name].
Co-administration of [HP016
trade name] with carbamazepine,
oxcarbazepine, phenobarbital,
phenytoin or other strong
inducers of CYP3A4 iscontraindicated (see section 4.3).

No dose adjustment of [HP016
trade name] or escitalopram isrequired.

↔Escitalopram
AUC: 1.05 (1.02, 1.08)
Cmax: 1.00 (0.92, 1.08)
Cmin: 1.10 (1.04, 1.16)
ANTIFUNGALS
Ketoconazole 400 mg once daily(daclatasvir 10 mg single dose)

Itraconazole
Posaconazole
Voriconazole↑ Daclatasvir
AUC: 3.00 (2.62, 3.44)
Cmax: 1.57 (1.31, 1.88)
CYP3A4 inhibition by
ketoconazoleInteraction not studied.
Expected due to CYP3A4
inhibition by the antifungal:
Page 9 of 21

The dose of daclatasvir should be
reduced when co-administeredwith ketoconazole or other strong
inhibitors of CYP3A4 (seesection 4.2).

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas

WHOPAR Part 4Interaction

December 2023

Recommendations concerning
co-administration↑ Daclatasvir
FluconazoleInteraction not studied.
Expected due to CYP3A4
inhibition by the antifungal:↑ Daclatasvir↔ Fluconazole

ANTIMYCOBACTERIALS
Rifampicin 600 mg once daily(daclatasvir 60 mg single dose)

Rifabutin
Rifapentine↓ Daclatasvir
AUC: 0.21 (0.19, 0.23)
Cmax: 0.44 (0.40, 0.48)
CYP3A4 induction byrifampicin
Interaction not studied.
Expected due to CYP3A4
induction by the
antimycobacterial:

Modest increases inconcentrations of daclatasvir are
expected, but no dose adjustmentof [HP016 trade name] or
fluconazole is required.

Co-administration of [HP016
trade name] with rifampicin,
rifabutin, rifapentine or otherstrong inducers of CYP3A4 iscontraindicated (see section 4.3).

↓ Daclatasvir
CARDIOVASCULAR AGENTS
Antiarrhythmics
Digoxin 0.125 mg once daily↑ Digoxin(daclatasvir 60 mg once daily)
AUC: 1.27 (1.20, 1.34)
Cmax: 1.65 (1.52, 1.80)
Cmin: 1.18 (1.09, 1.28)
P-gp inhibition by daclatasvir

Amiodarone

Calcium channel blockers
Diltiazem
Nifedipine
Amlodipine

Interaction not studied.

Interaction not studied.
Expected due to CYP3A4
inhibition by the calcium
channel blocker:

Digoxin should be used withcaution when co-administeredwith [HP016 trade name]. The
lowest dose of digoxin should beinitially prescribed. The serum
digoxin concentrations should bemonitored and used for titrationof digoxin dose to obtain thedesired clinical effect.
Use only if no other alternative isavailable. Close monitoring is
recommended if this medicinal
product is administered with
[HP016 trade name] incombination with sofosbuvir (seesections 4.4 and 4.8).
Caution is advised if [HP016
trade name] is co-administeredwith calcium channel blockers.

↑ Daclatasvir
VerapamilInteraction not studied.
Expected due to CYP3A4 andP-gp inhibition by verapamil:↑ Daclatasvir
Page 10 of 21

Caution is advised if [HP016
trade name] is co-administeredwith calcium channel blockers.

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas
CORTICOSTEROIDS
Systemic dexamethasone

WHOPAR Part 4Interaction

Recommendations concerning
co-administration

Interaction not studied.
Expected due to CYP3A4
induction by dexamethasone:

Co-administration of [HP016
trade name] with systemic
dexamethasone or other strong
inducers of CYP3A4 iscontraindicated (see section 4.3).

↓ Daclatasvir
HERBAL SUPPLEMENTS
St. John’s wort (Hypericum
perforatum)

December 2023

Interaction not studied.
Expected due to CYP3A4
induction by St. John’s wort:↓ Daclatasvir

Co-administration of [HP016
trade name] with St. John’s wortor other strong inducers of
CYP3A4 is contraindicated (seesection 4.3).

HORMONAL CONTRACEPTIVES
Ethinylestradiol 35 μg once
daily for 21 days + norgestimate
0.180/0.215/0.250 mg once dailyfor 7/7/7 days
(daclatasvir 60 mg once daily)↔ Ethinylestradiol
AUC: 1.01 (0.95, 1.07)
Cmax: 1.11 (1.02, 1.20)↔ Norelgestromin
AUC: 1.12 (1.06, 1.17)
Cmax: 1.06 (0.99, 1.14)

If an oral contraceptive is needed
during treatment with [HP016
trade name], it should containethinylestradiol 35 g andnorgestimate 0.180/0.215/0.250
mg. Other oral contraceptives
have not been studied.

↔ Norgestrel
AUC: 1.12 (1.02, 1.23)
Cmax: 1.07 (0.99, 1.16)
IMMUNOSUPPRESSANTS
Cyclosporine 400 mg single
dose(daclatasvir 60 mg once daily)↔ Daclatasvir
AUC: 1.40 (1.29, 1.53)
Cmax: 1.04 (0.94, 1.15)
Cmin: 1.56 (1.41, 1.71)↔ Cyclosporine
AUC: 1.03 (0.97, 1.09)
Cmax: 0.96 (0.91, 1.02)

Tacrolimus 5 mg single dose
(daclatasvir 60 mg once daily)

Sirolimus
Mycophenolate mofetil↔ Daclatasvir
AUC: 1.05 (1.03, 1.07)
Cmax: 1.07 (1.02, 1.12)
Cmin: 1.10 (1.03, 1.19)↔ Tacrolimus
AUC: 1.00 (0.88, 1.13)
Cmax: 1.05 (0.90, 1.23)
Interaction not studied.
Expected:↔ Daclatasvir↔ ImmunosuppressantPage 11 of 21

No dose adjustment of either
medicinal product is required
when [HP016 trade name] is coadministered with cyclosporine,
tacrolimus, sirolimus or
mycophenolate mofetil.

Daclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas
LIPID LOWERING AGENTS
HMG-CoA reductase inhibitors
Rosuvastatin 10 mg single dose
(daclatasvir 60 mg once daily)

Atorvastatin
Fluvastatin
Simvastatin
Pitavastatin
Pravastatin
NARCOTIC ANALGESICS
Buprenorphine/naloxone, 8/2
mg to 24/6 mg once daily
individualized dose*(daclatasvir 60 mg once daily)* Evaluated in opioid-dependent
adults on stablebuprenorphine/naloxone
maintenance therapy.

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December 2023

Interaction

Recommendations concerning
co-administration↑ Rosuvastatin
AUC: 1.58 (1.44, 1.74)
Cmax: 2.04 (1.83, 2.26)
Inhibition of OATP 1B1 and
BCRP by daclatasvir
Interaction not studied.
Expected due to inhibition of
OATP 1B1 and/or BCRP by
daclatasvir:

Caution should be used when
[HP016 trade name] is coadministered with rosuvastatin orother substrates of OATP 1B1 or
BCRP.

↑ Concentration of statin↔ Daclatasvir
AUC: ↔*
Cmax: ↔*
Cmin: ↔*

No dose adjustment of [HP016
trade name] or buprenorphine
may be required, but it isrecommended that patients should
be monitored for signs of opiate
toxicity.

↑ Buprenorphine
AUC: 1.37 (1.24, 1.52)
Cmax: 1.30 (1.03, 1.64)
Cmin: 1.17 (1.03, 1.32)↑ Norbuprenorphine
AUC: 1.62 (1.30, 2.02)
Cmax: 1.65 (1.38, 1.99)
Cmin: 1.46 (1.12, 1.89)*Compared with historical data.

Methadone, 40-120 mg once
daily individualized dose*(daclatasvir 60 mg once daily)* Evaluated in opioid-dependent
adults on stable methadone
maintenance therapy.

↔ Daclatasvir
AUC: ↔*

No dose adjustment of [HP016
trade name] or methadone isrequired.

Cmax: ↔*
Cmin: ↔*
↔ R-methadone
AUC: 1.08 (0.94, 1.24)
Cmax: 1.07 (0.97, 1.18)
Cmin: 1.08 (0.93, 1.26)*Compared with historical data.

SEDATIVES
Benzodiazepines
Midazolam 5 mg single dose
(daclatasvir 60 mg once daily)↔ Midazolam
AUC: 0.87 (0.83, 0.92)
Cmax: 0.95 (0.88, 1.04)
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No dose adjustment of
midazolam, otherbenzodiazepines or otherDaclatasvir (dihydrochloride) 60mg
tablets (Mylan Laboratories), HP016

Medicinal products by
therapeutic areas
Triazolam
Alprazolam

WHOPAR Part 4Interaction
Interaction not studied.
Expected:↔ Triazolam

December 2023

Recommendations concerning
co-administration
CYP3A4 substrates is required
when co-administered with
[HP016 trade name].

↔ Alprazolam
No clinically relevant effects on the pharmacokinetics of either medicinal product are expected whendaclatasvir is co-administered with any of the following: PDE-5 inhibitors, medicinal products in the ACE
inhibitor class (e.g. enalapril), medicinal products in the angiotensin II receptor antagonist class (e.g.
losartan, irbesartan, olmesartan, candesartan, valsartan), disopyramide, propafenone, flecainide, mexilitine,quinidine or antacids.
Paediatric population
Interaction studies have only been performed in adults.
4.6

Fertility, pregnancy and breastfeeding

Women of childbearing potential
Pregnancy should be avoided in women treated with daclatasvir. Use of highly effective contraception
should be continued for 5 weeks after completion of therapy with [HP016 trade name] (see section 4.5 foradditional information on use with hormonal contraceptives).
Pregnancy
There are no data from the use of daclatasvir in pregnant women. Studies of daclatasvir in animals haveshown embryotoxic and teratogenic effects (see section 5.3).
The potential risk for humans is unknown.
[HP016 trade name] should not be used during pregnancy or in women of childbearing potential not using
contraception (see section 4.4). Use of highly effective contraception should be continued for 5 weeks after
completion of therapy with (see section 4.5).
Since [HP016 trade name] must be used in combination with sofosbuvir, the contraindications and warnings
for this medicinal product are applicable.
Breastfeeding
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 (see section 5.3). A risk to thenewborn/infant cannot be excluded. Mothers should be instructed not to breastfeed if they are taking [HP016
trade name].
Fertility
No human data on the effect of daclatasvir on fertility are available. In rats, no effect on mating or fertility
was seen (see section 5.3).
4.7

Effects on ability to drive and use machines

Dizziness and tiredness have been reported during treatment with daclatasvir in combination with otherhepatitis C medicines. If affected, patients should not drive or operate machinery.

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Undesirable effects

Summary of the safety profile
The most frequently reported adverse reactions with daclatasvir plus sofosbuvir are fatigue, headache andnausea, usually mild. Anaemia was also reported very commonly from studies where daclatasvir was given
with sofosbuvir with or without ribavirin.
Tabulated list of adverse reactions
Adverse reactions to [HP016 trade name] from controlled trials with daclatasvir in combination with
sofosbuvir (with or without ribavirin) or peginterferon alfa and ribavarin are presented in the table below.
Adverse drug reactions are listed by system organ class (SOC) and frequency. Frequency categories aredefined as follows: very common (at least 1 in 10), common (1 in 100 to 1 in 10) and uncommon (1 in 1000
to 1 in 100).
Blood and lymphatic system disorders
Very common

anaemia

Metabolism and nutrition disorders
Commondecreased appetite

Psychiatric disorders
Commoninsomnia, irritability

Nervous system disorders
Very common

headacheCommondizziness, migraine

Vascular disorders
Commonhot flush

Respiratory, thoracic and mediastinal disorders
Commondyspnoea, dyspnoea exertional, cough, nasal congestion

Gastrointestinal disorders
Very common

nauseaCommondiarrhoea, vomiting, abdominal pain, gastroesophageal reflux disease, constipation, drymouth, flatulence

Skin and subcutaneous tissue disorders
Commonrash, alopecia, pruritus, dry skinMusculoskeletal and connective tissue disorders
Commonarthralgia, myalgia

General disorders
Very common

fatigue

Laboratory abnormalities
In clinical studies of daclatasvir in combination with sofosbuvir with or without ribavirin, 2% of patients had
Grade 3 haemoglobin decreases; all of these patients received daclatasvir + sofosbuvir + ribavirin. Grade 3/4
increases in total bilirubin were observed in 5% of patients (all in patients with HIV coinfection who werereceiving concomitant atazanavir, with Child-Pugh A, B, or C cirrhosis, or who were post-liver transplant).

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Description of selected adverse reactions
Cardiac arrhythmias
Cases of severe bradycardia and heart block have been observed when daclatasvir is used in combination
with sofosbuvir and concomitant amiodarone and/or other drugs that lower the heart rate (see sections 4.4
and 4.5).
Reporting of suspected adverse reactions
Health care providers are asked to report adverse reactions that may be linked to a medicine, to the marketing
authorisation holder, or, if available, to the national reporting system. Reports of suspected adverse reactions
to a medicine are important for the monitoring of the medicine’s benefits and risks.For reporting of adverse
events and PV related queries please write to Email: ProductSafety@viatris.com
4.9

Overdose

Symptoms
There is limited experience of accidental overdose of daclatasvir in clinical studies. In phase 1 clinicalstudies, healthy subjects who received up to 100 mg once daily for up to 14 days or single doses up to
200 mg had no unexpected adverse reactions.
Treatment
There is no known antidote for overdose of daclatasvir. Treatment of overdose with daclatasvir should
consist of general supportive measures, including monitoring of vital signs, and observation of the patient’s
clinical status. Because daclatasvir is highly protein bound (99%) and has a molecular weight >500, dialysis
is unlikely to significantly reduce plasma concentrations of daclatasvir.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Direct-acting antiviral, ATC code: J05AP07
Mechanism of action
Daclatasvir is an inhibitor of non-structural protein 5A (NS5A), a multifunctional protein that is an essential
component of the HCV replication complex. Daclatasvir inhibits both viral RNA replication and virion
assembly.
Clinical efficacy and safety
A WHO-commissioned systematic review identified 142 clinical studies that evaluated the safety andefficacy of various FDA- and EMA-approved DAA regimens, including sofosbuvir/daclatasvir.
Sofosbuvir/daclatasvir in HCV infected adults without cirrhosis
In a combined analysis of treatment-naïve and treatment-experienced persons treated with
sofosbuvir/daclatasvir, the pooled SVR rates exceeded 92% for infection with genotypes 1, 2, 3 and 4. Data
from an observational study (MSF demonstration project) provided information on the less commonly
reported genotypes 5 and 6. A total of eight persons with genotype 5 and 123 persons with genotype 6
infection were treated with sofosbuvir/daclatasvir for 12 weeks. SVR rates were 88% and 94% for genotypes
5 and 6 respectively.
Sofosbuvir/daclatasvir in HCV infected adults with compensated cirrhosis
In a combined analysis of treatment-naive and treatment-experienced persons with compensated cirrhosis(Child Pugh A or B) treated with sofosbuvir/daclatasvir for 12 weeks, the pooled SVR rates exceeded 93%
for infection with genotypes 1 and 2. SVR rates for infection with genotype 3 were low, ranging from 79% to82%. However, after 24 weeks of treatment, SVR rates increased to 90%. Data from an observational study
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(MSF demonstration project) provided information on genotypes 5 and 6, and real-world data from Egypt
provided information on genotype 4. One cirrhotic person with genotype 5 infection treated with
sofosbuvir/daclatasvir for 12 weeks reached SVR. Among 185 cirrhotic persons with genotype 6 infection
treated with sofosbuvir/daclatasvir for 12 weeks, 92% reached SVR. Cirrhotic persons with genotype 4
infection had SVR rates that exceeded 98% after 12 weeks of treatment.
Sofosbuvir/daclatasvir in HCV infected adults with decompensated cirrhosis
There are currently insufficient data to provide definitive treatment guidelines for HCV infected adults withdecompensated cirrhosis (Child Pugh C). It is recommended that such individuals are treated with
sofosbuvir/daclatasvir for 24 weeks using the same regimen as used for individuals with compensatedcirrhosis.
HCV/HIV co-infection
HCV treatment outcomes with daclatasvir/sofosbuvir are comparable in persons with HIV/HCV coinfection
to those with HCV monoinfection. Because DAAs are safe and effective for people with HIV/HCV, there is
no longer any need to consider them as a special or difficult-to-treat population. However, there areimportant DDIs (drug-drug interactions) with pangenotypic HCV regimens and antiretroviral therapies forHIV. Therefore, checking for DDIs between HCV and HIV medications should be emphasized. The dose of
daclatasvir may need to be increased or decreased when used concomitantly with cytochrome P450 3A/4
inducers and inhibitors, respectively. See Section 4.5.
Safety of sofosbuvir/daclatasvir
Treatment discontinuation due to adverse events was very low in persons without and with cirrhosis (<1%).
Similar results were observed in treatment-naive and treatment-experienced persons.
Long term efficacy data
In a follow-up study of 258 patients who achieved SVR12 with daclatasvir and sofosbuvir with a median
duration of post-SVR12 follow-up of 38 months, no relapses occurred (with relapses defined as confirmed orlast available HCV RNA ≥ LLOQ).
Impact of baseline NS5A RAVs on cure rates
Baseline NS5A resistance-associated variants (RAVs) had no major impact on cure rates in patients treatedwith sofosbuvir + daclatasvir, with the exception of the Y93H RAV in genotype 3 infection (seen in 16/192[8%] of patients). The SVR12 rate in genotype-3 infected patients with this RAV is reduced (in practice as
relapse after end of treatment response), especially in patients with cirrhosis. The overall cure rate forgenotype-3 infected patients who were treated for 12 weeks with sofosbuvir + daclatasvir in the presence andabsence of the Y93H RAV was 7/13 (54%) and 134/145 (92%), respectively.
Paediatric population
A WHO-commissioned systematic review and meta-analysis of the efficacy and safety of key DAA
regimens was undertaken for adolescents (12–18 years), older children (6–11 years) and younger children(3–5 years) with chronic hepatitis C virus infection, based on the same age groupings used in the trials forregulatory approval. There were 49 studies (three RCTS, 28 non-RCTs and 18 observational studies).
Together, they reported treatment experience in 1891 adolescents (35 study arms), 472 older children (13study arms) and 167 younger children (7 study arms). There were no placebo-controlled RCTs, and findings
were based on summary estimates of SVR cure rates by regimen in the three age groups. However, thesewere considered informative because spontaneous clearance is rare in the absence of treatment. Data on
serious adverse events and treatment discontinuations were considered more informative than adverse events
alone because of the lack of a comparison group. The majority of participants were non-cirrhotic (1786,
70.6%), treatment-naïve (1825, 72.1%), and with non-GT3 infection (1453, 57.4%).
Overall, sustained virological response rates 12 weeks after the end of treatment (SVR12) were high (≥95%)in all age groups and for the key pangenotypic DAA regimens (sofosbuvir/daclatasvir, sofosbuvir/velpatasvir
and glecaprevir/pibrentasvir) as well as for sofosbuvir/ledipasvir. In particular, among the 183 adolescents
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(12 to 17 years) who received sofosbuvir/daclatasvir, SVR12 was 99% (96–100). Among the 34 older
children (6 to 11 years) who received sofosbuvir/daclatasvir, SVR12 was 100% (94–100). There were no
study data for sofosbuvir/daclatasvir in younger children (3 to 5 years).
The rate of any adverse event with pangenotypic DAA regimens was higher for children ages 3–5 years(72%) than for those ages 6–11 years (53%) or adolescents (50%), but serious adverse events and treatment
discontinuations were uncommon (<1%), except in young children (6.6%) because of the poor palatability ofthe oral formulation of sofosbuvir/velpatasvir in this group. Less than half of the studies (22/49 (44.9%))
reported information on comorbidities. There were 15 persons with cirrhosis across nine studies, 304 persons
who were treatment-experienced across 21 studies and 157 persons with GT3 infection across eight studies.
There were no studies of sofosbuvir/ daclatasvir in children or adolescents reported from sub-Saharan Africa,
where HCV genotype 4 non-a/d subtypes are endemic in some regions, as well as other genotypes (including
genotype 1 and 3) that frequently contain resistance-associated substitutions in the NS5A regions. This may
contribute to higher rates of treatment failure with sofosbuvir/daclatasvir.
5.2

Pharmacokinetic properties

The absorption characteristics of [HP016 trade name] have been determined after administration of one
tablet in healthy volunteers in the fasting state as follows:
Pharmacokinetic variable’

Mean value* (± standard deviation)
Daclatasvir (dihydrochloride)

Maximum concentration (Cmax)

2003 ± 492 µg/ml

Area under the curve (AUC0–∞), a
measure of the extent of absorption

21786 ± 6287 µg.h/ml

Time to attain maximum concentration(tmax)

1.28 ± 0.54 h* arithmetic mean
Pharmacokinetics of daclatasvir
Daclatasvir
GeneralThe pharmacokinetic properties of daclatasvir were evaluated in healthy
adult subjects and in patients with chronic HCV.
Absorption
Absolute bioavailability
Oral bioavailability

The absolute bioavailability of the tablet formulation is 67%.
At least 67%.

Food effect

AUC(0-∞)
With highfat mealWith lightmeal

Distribution
Volume of distribution(mean)

Cmax

Tmax

23%↓

28%↓

NA*

No change

No changeNA*

Approximately 47 L.
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Plasma protein binding
Tissue distribution
Metabolism

Active metabolite(s)Elimination
General note
Elimination half life
Mean systemic clearance(Cl/F)% of dose excreted in urine% of dose excreted in faeces
Pharmacokinetic linearity
Drug interactions (in vitro)
Transporters

Metabolizing enzymes

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December 2023

Approximately 99% (independent of dose between 1 mg to 100 mg)
Active and passive transport into hepatocytes.
Substrate of CYP3A with CYP3A4 being the major isoform responsible
for metabolism.
None.
Daclatasvir is mainly cleared by the liver.
12 to 15 h
4.24 L/h
6.6% (primarily as unchanged drug)
88% (53% as unchanged drug)
Daclatasvir Cmax, AUC and Cmin increase in a near dose-proportionalmannerNA*
In vitro and in vivo studies showed that daclatasvir is a substrate of P-gp.
Daclatasvir is an inhibitor of P-gp, OATP 1B1 and BCRP.
Active transport into hepatocytes by OCT1 and other unidentified uptake
transporters.
In vitro daclatasvir is an inhibitor of renal uptake transporters, OAT1 and
3, and OCT2, but is not expected to have a clinical effect on thepharmacokinetics of substrates of these transporters.
In vitro and in vivo studies demonstrate that daclatasvir is a substrate of
CYP3A, with CYP3A4 being the major CYP isoform responsible for the
metabolism. Daclatasvir in vitro did not inhibit CYP enzymes 1A2, 2B6,
2C8, 2C9, 2C19, or 2D6.

*Information not available

Pharmacokinetics in special clinical situations
Renal impairment
The pharmacokinetics of daclatasvir following a single 60 mg oral dose were studied in non-HCV infectedsubjects with renal impairment. Daclatasvir unbound AUC was estimated to be 18%, 39% and 51% higher
for subjects with creatinine clearance (CLcr) values of 60, 30 and 15 ml/min, respectively, relative tosubjects with normal renal function. Subjects with end-stage renal disease requiring haemodialysis had a
27% increase in daclatasvir AUC and a 20% increase in unbound AUC compared to subjects with normal
renal function.
Hepatic impairment
The pharmacokinetics of daclatasvir following a single 30 mg oral dose were studied in non-HCV infectedsubjects with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic
impairment compared with unimpaired subjects. The Cmax and AUC of total daclatasvir (free and proteinbound drug) were lower in subjects with hepatic impairment; however, hepatic impairment did not have aclinically significant effect on the free drug concentrations of daclatasvir.
Elderly
Population pharmacokinetic analysis of data from clinical studies indicated that age had no apparent effecton the pharmacokinetics of daclatasvir.

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GenderPopulation pharmacokinetic analysis identified gender as a statistically significant covariate on daclatasvir
apparent oral clearance (CL/F) with female subjects having slightly lower CL/F, but the magnitude of theeffect on daclatasvir exposure is not clinically important.
Race
Population pharmacokinetic analysis of data from clinical studies identified race (categories “other”[patients who are not white, black or Asian] and “black”) as a statistically significant covariate on
daclatasvir apparent oral clearance (CL/F) and apparent volume of distribution (Vc/F) resulting in slightly
higher exposures compared to white patients, but the magnitude of the effect on daclatasvir exposure is notclinically important.
5.3

Preclinical safety data

General toxicity
In repeat-dose toxicology studies in animals, hepatic effects (Kupffer-cell hypertrophy/ hyperplasia,
mononuclear cell infiltrates and bile duct hyperplasia) and adrenal gland effects (changes in cytoplasmic
vacuolation and adrenal cortical hypertrophy/hyperplasia) were observed at exposures similar or slightly
higher than the clinical AUC exposure. In dogs, bone marrow hypocellularity with correlating clinicalpathology changes were observed at exposures 9-fold the clinical AUC exposure. None of these effects havebeen observed in humans.
Mutagenicity/ Carcinogenicity
Daclatasvir was not carcinogenic in mice or in rats at exposures 8-fold or 4-fold, respectively, the clinical
AUC exposure. No evidence of mutagenic or clastogenic activity was observed in in vitro mutagenesis(Ames) tests, mammalian mutation assays in Chinese hamster ovary cells, or in an in vivo oral micronucleus
study in rats.
Reproductive toxicity
Daclatasvir is embryotoxic and teratogenic in rats and rabbits at exposures at or above 4-fold (rat) and 16fold (rabbit) the clinical AUC exposure. Developmental toxicity consisted of increased embryofoetal
lethality, reduced fetal body weights and increased incidence of fetal malformations and variations. In rats,
malformations mainly affected the brain, skull, eyes, ears, nose, lip, palate or limbs and in rabbits, the ribs
and cardiovascular area. Maternal toxicity including mortality, abortions, adverse clinical signs, decreases inbody weight and food consumption was noted in both species at exposures 25-fold (rat) and 72-fold (rabbit)
the clinical AUC exposure.
In a study of pre- and post-natal development in rats, there was neither maternal nor developmental toxicity
at doses up to 50 mg/kg/day, associated with AUC values 2-fold the clinical AUC exposure. At the highest
dose (100 mg/kg/day), maternal toxicity included mortality and dystocia; developmental toxicity included
slight reductions in offspring viability in the peri- and neonatal periods; and reductions in birth weight thatpersisted into adulthood. The AUC value associated with this dose is 4-fold the clinical AUC exposure.
Daclatasvir had no effects on fertility in female rats at any dose tested. The highest AUC value in unaffected
females was 18-fold the clinical AUC exposure. In male rats, effects on reproductive endpoints were limited
to reduced prostate/seminal vesicle weights, and minimally increased dysmorphic sperm at 200 mg/kg/day;
however, neither finding adversely affected fertility nor the number of viable conceptuses sired. The AUC
associated with this dose in males is 19-fold the clinical AUC exposure.
Daclatasvir was excreted into the milk of lactating rats with concentrations 1.7- to 2-fold maternal plasma
levels.

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6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Core tablet:

December 2023

Anhydrous lactose
silicified microcrystalline cellulose
croscarmellose sodium
magnesium stearate
colloidal anhydrous silica.

Film coat:

Hypromellose
titanium dioxide
macrogoliron oxide yellow
FD&C blue #2/ Indigo carmine aluminium lake

This medicine is essentially ‘sodium-free’. It contains less than 1 mmol sodium (23 mg) per tablet.
6.2

Incompatibilities

Not applicable.
6.3

Shelf life

36 months
6.4

Special precautions for storage

Do not store above 30°C. Store in the original container.
6.5

Nature and contents of container

HDPE
Round, blue opaque high density polyethylene (HDPE) bottle with a blue opaque polypropylene screw orchild resistant closure, with wad containing aluminium induction sealing liner.
Pack size: 28 tablets.
6.6

Special precautions for disposal and other handlingNo special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.

7.

SUPPLIER

Mylan Laboratories Limited
Plot No.564/A/22, Road No. 92, Jubilee Hills
Hyderabad – 500096
Telangana
India
Email: ProductSafety@viatris.com

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8.

WHOPAR Part 4

December 2023

WHO REFERENCE NUMBER (WHO Prequalification Programme)

HP016

9.

DATE OF PREQUALIFICATION

15 May 201910.

DATE OF REVISION OF THE TEXT

December 2023
References
GeneralWorld Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus
infection. 2018. Available at:https://apps.who.int/iris/bitstream/handle/10665/273174/9789241550345-eng.pdf
World Health Organization. Updated recommendations on treatment of adolescents and children with chronic HCV
infection, and HCV simplified service delivery and diagnostics. 2022. Available at:https://iris.who.int/bitstream/handle/10665/363590/9789240052734-eng.pdf?sequence=1
Daklinza 30 and 60 mg film-coated tablets: product information. European Medicines Agency; 22 August 2014(https://www.ema.europa.eu/en/documents/product-information/daklinza-epar-product-information_en.pdf).
Daklinza (daclatasvir) tablets for oral use: highlights of prescribing information. US Food and Drug Administration;
February 2017 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206843s006lbl.pdf).
Section 4.5
University of Liverpool, HEP and HIV Drug interactions, available at:
http://www.hep-druginteractions.org
http://www.hiv-druginteractions.org[All links accessed in November 2023]

Detailed information on this medicine is available on the World Health Organization (WHO) website:
https://extranet.who.int/prequal/medicines/prequalified/finished-pharmaceutical-products

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