Safety of direct acting antiviral treatment for hepatitis C in oncologic setting: A clinical experience and a literature review

Table 1 Currently used direct aging antiviral characteristics

Trade name	Compound	Year of FDA/EMA approval	Mechanism of action	Pharmaceutical form	Dose	Genotypes
Zepatier	Elbasvir/grazoprevir	2016	NS5A inhibitor/protease inhibitor	Film-coated tablet	50 mg/100 mg qd	1a, 1b, 4
Epclusa	Sofosbuvir/velpatasvir	2016	NS5B inhibitor/ NS5A inhibitor	Film-coated tablet	400 mg/100 mg	Pangenotypic
Maviret	Glecaprevir/pibrentasvir	2017	Protease inhibitor/NS5A inhibitor	Film-coated tablet	100 mg/40 mg qd	Pangenotypic
Vosevi	Sofosbuvir/velpatasvir/voxilaprevir	2018/2017	NS5B inhibitor /NS5A inhibitor/protease inhibitor	Film-coated tablet	400 mg/100 mg/100 mg	Pangenotypic

DAA: Direct aging antiviral; FDA: Food and drug administration; EMA: European Medicines Agency.

Table 2 Pharmacokinetics of currently used direct aging antivirals

DAAs		Absorption				Distribution		Metabolism	Excretion
Tradename	Compound	Tmax (h)	Cmax (ng/mL)	Cmin (ng/mL)	AUC (ng∙h/mL)	Vd/F	Protein binding (%)	Substrate of	T ½, (h)
Zepatier	Elbasvir	3	121	48.4	1920	680	> 99.9	P-gp	31
	Grazoprevir	2	165	18.0	1420	1250	> 98.8	P-gp	24
Epclusa	Sofosbuvir	0.5-1/3	566/868	NR	1260/13970	NR	61-65 minim	P-gp and BCRP	0.5/25
	Velpatasvir	4	311	NR	2970	NR	> 99.5	P-gp, OATP1B, and BCRP	15
Maviret	Glecaprevir	5.0	597	NR	4800	NR	97	P-gp	6-9
	Pibrentasvir	5.0	110	NR	1430	NR	> 99.9	P-gp	23-29
Vosevi	Sofosbuvir	2/4	678/744	NR	1665/12,834	NR	61-65 minim	P-gp and BCRP	0.5/29
	Velpatasvir	4	311	NR	4041	NR	> 99	P-gp, OATP1B1/3, and BCRP	17
	Voxilaprevir	4	192	47	2577	NR	> 99	P-gp and BCRP	33

DAAs: Direct aging antivirals; NR: Data not reported and/or available; T ½: Elimination half time.

Table 3 Pharmacodynamics of currently used direct aging antivirals

Trade name	Compound	Efficacy	Toxicity
Zepatier	Elbasvir/grazoprevir	Effective regimen used for 12 wk against HCV genotype 1 and 4. Approved for patients with renal insufficiency and compensated cirrhosis. Fixed dose combination of 50 mg/100 mg once daily. Favourable safety profile with low discontinuation rates (< 5%)	Fatigue, headache, asthenia, nausea, rash, ALT/AST and ALP increase
Epclusa	Sofosbuvir/velpatasvir	Treatment for 12 wk highly effective in both treatment-experienced and treatment-naïve HCV pangenotypic patients	Fatigue, headache, nausea and insomnia. Combination therapy with ribavirin led to anaemia in over 10% of patients
Maviret	Glecaprevir/pibrentasvir	Pangenotypic highly effective regimen. Administered for 8 to 12 wk once daily at doses of 100 mg/40 mg. Naïve and experienced patients with or without cirrhosis	Headache, fatigue, nasopharyngitis and nausea
Vosevi	Sofosbuvir/velpatasvir/voxilaprevir	Pangenotypic, highly effective, licenced for patients in whom IFN/riba and DAAs failed	Headache, diarrhoea, fatigue, nausea and constipation

ALT: Alanine transaminase; AST: Aspartate transaminase; DAAs: Direct aging antivirals; HCV: Hepatitis C virus; IFN: Interferon.

Table 4 Chemotherapy drug classes employed

Chemotherapy drug classes	Examples
Platinum-containing agents	(Cisplatin, carboplatin, oxaliplatin)
Folate antagonists	(Methotrexate, pemetrexed)
Pyrimidine compounds	(Fluorouracil, capecitabine, cytarabine, gemcitabine, decitabine)
Purine analogues	(Mercaptopurine, fludarabine, cladribine, clofarabine)
Alkylating agents	(Cyclophosphamide, ifosfamide, melphalan, bendamustine, busulfan)
Anthracyclines	(Daunorubicin, doxorubicin, epirubicin, idarubicin, bleomycin)
Topoisomerases	(Topotecan, etoposide, irinotecan)
Cytidine analogues	(Azacytidine, decitabine)
Immunosuppressants	(Tacrolimus, cyclosporine)
Immunomodulatory drugs	(Ienalidomide, thalidomide)
Mitotic inhibitors	(Paclitaxel, docetaxel, vinblastine, vincristine)
Hormonal therapies	(Tamoxifen)
Targeted therapies other than rituximab	(e.g., cetuximab, bortezomib, alemtuzumab)