hepatitis c

1. H
E
P
A
T
I
T
I
S
C

2. • “Hepa” means Liver
• “Titis” means Inflammation
• Hepatitis is an inflammation of
the liver.
• Infectious (i.e. viral, bacterial,
fungal, and parasitic organisms)
• Non-infectious (e.g. alcohol).
INTRODUCTION

3. TYPES OF HEPATITIS

4. • Hepatitis C is a contagious liver disease that results from infection with the Hepatitis
C virus (HCV).
• Two types:
1 Acute
 Short-term illness
 Occurs within the first 6 months after someone is exposed to the HCV.
2 Chronic:
 Acute infection leads to chronic infection.
 Long-term health problems, or even death.
HEPATITIS C

5. SOURCES OF INFECTION FOR
PERSONS WITH HEPATITIS C
*Nosocomial; Health-care work; Perinatal
Source: Centers for Disease Control and Prevention
Dr.T.V.Rao MD

6. EPIDEMIOLOGY
• The WHO estimates about 3% of the world’s population has been
infected with HCV.
• More than 170 million chronic carriers who are at risk of developing
liver cirrhosis and/or liver cancer.
• Severe morbidity in 20-30% of infected persons.

7. Source: Centers for Disease Control and Prevention

8. TREATMENT & MEDICATIONS

10. HCV PROTEASE INHIBITORS

11. SIMEPREVIR
Brand Names Olysio Galexos
Pharmacokinetics
Absorption:
Food increases
systemic exposure
by 60-70%
Distribution:
Protein bound
>99.9%
Metabolism:
Liver
Excretion:
Hepatobiliary
t1/2 : 41 hr (HCV+);
10-13 hr (HCV-)
Pharmacodynamics
Inhibit the proteolytic activity of recombinant genotype 1a and 1b HCV NS3/4A
proteases.
Dosing forms &
strengths:
Capsule 150mg.
Indications and Dosing
Chronic Hepatitis C
(genotype 1)
Treatment-naïve and
prior relapsed patients
150 mg PO qD for 12 weeks of treatment with simeprevir,
peginterferon alfa, and ribavirin FOLLOWED by an
additional 12 weeks of peginterferon alfa and ribavirin( with
cirrhosis).
Treatment-naïve or 150 mg PO qD plus sofosbuvir 400 mg for 12 weeks (without

12. Administration Oral
• Administer with food.
• Maintain adequate fluid intake.
• Swallow capsules whole.
Dosing
Considerations
Must not be used as monotherapy; if sofosbuvir, peginterferon alfa, or ribavirin is
discontinued for any reason, simeprevir must also be discontinued.
Adverse Effects Fatigue, headache ,dizziness, insomnia, Skin rash, pruritus, Nausea , diarrhea, Increased
serum bilirubin, Myalgia, Dyspnea
Contraindications Hypersensitivity, Pregnancy
Drug Interactions • Simeprevir may increase the serum concentration of Atorvastatin, Cisapride, CYP3A4
Substrates, Cyclosporine (Systemic).
• CYP3A4 Inducers may decrease the serum concentration of Simeprevir.
• Atazanavir and CYP3A4 Inhibitors may increase the serum concentration of
Simeprevir.
Storage Store below 30°C (86°F). Store in the original bottle. Protect from light.

13. HCV POLYMERASE INHIBITORS

14. SOFOSBUVIR
Brand Names Sovaldi
Pharmacokinetics
Absorption:
Well absorbed
Distribution:
Plasma bound
61-65%
Metabolism:
Hepatic
Excretion:
Urine
t1/2 : 0.4hr
Pharmacodynamics
Inhibitor of HCV NS5B RNA-dependent polymerase; hence suppresses viral
replication.
Dosing forms &
strengths
Tablet 400mg.
Indications and Dosing
Chronic Hepatitis C
Genotype 1 or 4
400 mg PO qDay plus ribavirin and peginterferon alfa for 12
weeks.
Genotype 2 400 mg PO qDay plus ribavirin for 12 weeks.
Genotype 3 400 mg PO qDay plus ribavirin for 24 weeks.

15. Administration Oral Take with or without food.
Dosing
Considerations
Must not be used as monotherapy; if peginterferon alfa, or ribavirin is discontinued for
any reason, sovaldi must also be discontinued.
Adverse Effects Fatigue, headache, dizziness, insomnia, Skin rash, pruritus, Nausea , diarrhea, chills,
anemia, Myalgia, Dyspnea, asthenia
Contraindications Hypersensitivity, Pregnancy or planning pregnancy, CrCl < 50 mL/min, pancreatitis,
hemoglobinopathy.
Drug Interactions Modafinil, Oxcarbazepine, P-glycoprotein/ABCB1 Inducers, Rifabutin, Rifapentine may
decrease the serum concentration of Sofosbuvir.
Storage Store below 30°C (86°F). Dispense only in original container.

16. COMBINATION PRODUCTS

17. LEDIPASVIR/SOFOSBUVIR
Brand Names Harvoni
Pharmacokinetics
Absorption:
Well absorbed
Distribution:
Protein binding
Ledipasvir:>99.8%;
Metabolism:
Ledipasvir: 47 h
Sofosbuvir: ~0.5 h
Excretion:
•Feces
•Urine
Pharmacodynamics
• Ledipasvir: Inhibits HCV NS5A protein, which is required for viral replication.
• Sofosbuvir: Inhibitor of HCV NS5B RNA-dependent polymerase; hence
suppresses viral replication.
Dosing forms &
strengths
Tablet 90mg/400mg.
Indications and Dosing
Chronic
Hepatitis C
(Genotype 1)
Treatment-naïve
1 tablet (90mg/400mg) PO qDay for 12 weeks (with or
without cirrhosis)
Treatment-experienced
1 tablet (90mg/400mg) PO qDay for 12 weeks (without
cirrhosis)
Treatment-experienced 1 tablet (90mg/400mg) PO qDay for 24 weeks (with cirrhosis)

18. Administration Oral
May take with or without food.
Dosing
Considerations
8 weeks can be considered in treatment-naïve patients without cirrhosis who have
pretreatment HCV RNA <6 million IU/mL.
Adverse Effects Fatigue, headache, dizziness, insomnia, Increased bilirubin, Increased lipase.
Cautions Do not use with other products that contain sofosbuvir (Sovaldi).
Drug
Interactions
• Sofosbuvir may enhance the bradycardic effect of Amiodarone.
• Antacids, H2-Antagonist & PPIs may decrease the serum concentration of Ledipasvir.
• Sofosbuvir may increase the serum concentration of Topotecan, Vincristine, rifaximin &
rosuvastatin.
Storage Store below 30°C (86°F). Dispense in original container.

19. HCV NS5A INHIBITORS

20. DACLATASVIR
Brand Names Daklinza
Pharmacokinetics
Absorption:
Bioavailability
67%
Distribution:
Protein binding
99%
Metabolism:
Hepatic by CYP3A
Excretion:
•Feces
•Urine
Pharmacodynamics Inhibits NS5A, a nonstructural protein encoded by HCV, suppress viral replication.
Dosing forms &
strengths
Tablet 30mg/60mg.
Indications and Dosing
Chronic Hepatitis
C (Genotype 3)
60 mg (plus sofosbuvir 400 mg) PO qDay for 12 weeks.

21. Administration Oral May take with or without food.
Dosing
Considerations
If sofosbuvir is permanently discontinued in a patient receiving daclatasvir with
sofosbuvir, then daclatasvir should also be discontinued.
Adverse Effects Headache , Fatigue , Nausea , Diarrhea , Elevated lipase.
Contraindications Coadministration with drugs that strongly induce CYP3A and, thus, may lead to lower
exposure and loss of daclatasvir efficacy.
Drug Interactions • Daclatasvir may enhance the bradycardic effect of Amiodarone.
• CYP3A4 inducers may decrease the serum concentration of Daclatasvir.
• CYP3A4 inducers may increase the serum concentration of Daclatasvir.
• Daclatasvir may increase the serum concentration of HMG-CoA Reductase Inhibitors.
Storage Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

22. INTERFERONS & RIBAVARIN

23. INTERFERON ALFA-2B
Brand Names Intron-A
Pharmacokinetics
Absorption:
Bioavailability
•IM: 83%
•SC: 90%
Distribution:
•Vd: 31 L
•IFN does not
penetrate the CSF
Metabolism:
Renal
Excretion:
Elimination H.L
•IV: 2 hours
•IM: 2-3 hours
•SC: 2-3 hours
Pharmacodynamics
Inhibits HBV replication; immunomodulatory actions; may induce gene
transcription; interferes with oncogene expression, may change cell surface antigen
expression; cytotoxic activity of macrophages increases.
Dosing forms &
strengths
• Injectable solution 6 / 10 million International Units/mL (3.8 / 3.2 mL vial
respectively)
• Multi dose pen; 6 doses each; (22.5 / 37.5 / 75 million International
Units/1.5mL)
• Powder for injection (10 / 18 / 50 million International Units/vial)
Indications and Dosing
Chronic Hepatitis C 3 million units IM/SC 3 times/wk for16 wk.
Acute Hepatitis C 5 million Units SC/IM qd for 4 wk, then 3 times/wk for 20 wk.

24. Administration IV, IM, SC OR Intralesional.
Dosing
Considerations
For chronic hepatitis:
•If ALT normalized after 16 wk, continue treatment for 18-24 mo.
•If ALT not normalized or high levels of HCV RNA after 16 wk, consider discontinuing
treatment.
For acute hepatitis:
•If severe adverse reactions develop reduce dose by 50% or temporarily withhold until
adverse reactions abate.
•If intolerance persists discontinue permanently.
Adverse Effects Fatigue, Fever, Neutropenia, Flu-like syndrome, Myalgia, anorexia, nausea, weakness.
Contraindications Hypersensitivity, Autoimmune hepatitis, Decompensated liver disease
Drug Interactions • may increase the serum concentration of Methadone.
• may enhance the adverse/toxic effect of Ribavirin. Hemolytic anemia has been
observed.
Storage • Refrigerate intact vials.
• Powder & premixed solutions are stable at room temp for 7 d & for 30 d if
refrigerated.

25. INTERFERON ALFACON 1
Brand Names Infergen
Pharmacokinetics
• Pharmacokinetic studies have not been conducted on patients with chronic
hepatitis C.
• Time to peak: Healthy volunteers: 24-36 hours.
Pharmacodynamics
Release immunomodulatory cytokine that enhances phagocytic activity of
macrophages and cytotoxic activity of lymphocytes for target cells.
Dosing forms &
strengths:
Injectable solution : 9mcg/0.3mL & 15mcg/0.5mL.
Indications and Dosing
Chronic Hepatitis
C (Genotype 3)
• 9 mcg SC 3 times/week for 24 wk.
• 15 mcg SC with ribavirin qDay for up to 48 weeks.
 <75 kg: ribavirin 1 g PO divided q12hr.
 ≥75 kg: ribavirin 1.2 g PO divided q12hr.

26. Administration
• SC, 3 times/week, with at least 48 hours between doses.
• Allow to reach room temperature just prior to administration.
Dosing
Considerations
• If severe toxicity occurs: Reduce to 7.5 mcg SC 3 times/week or discontinue.
• Monitor: Hgb, WBC, Plt, LFTs, creatinine, thyroid.
Adverse Effects Headache, Fatigue, Fever, Rigors, Myalgia, Body pain, Back pain, Arthalagia.
Contraindications • Hypersensitivity
• Decompensated liver disease
• Autoimmune hepatitis
Drug Interactions • Interferons may decrease the metabolism of Theophylline Derivatives.
• Interferons may enhance the adverse/toxic effect of Zidovudine.
• Interferons may decrease the metabolism of Zidovudine.
Storage • Store in refrigerator 2°C to 8°C. Do not freeze.
• Avoid exposure to direct sunlight.
• Do not shake vigorously.

27. PEGYLATED INTERFERON ALFA-
2A
Brand Names Pegasys
Pharmacokinetics
• Elimination Half-life:160 hours
• Time to peak serum: 72 to 96 hours
Pharmacodynamics
Release immunomodulatory cytokine that enhances phagocytic activity of
macrophages and cytotoxic activity of lymphocytes for target cells.
Dosing forms &
strengths
• Vial for single use: 180mcg/ml
• Prefilled syringe for single use: 180mcg/0.5ml
• Autoinjector for single use: 135 or 180 mcg/0.5ml
Indications and Dosing
C H C
• With other anti viral drugs:
 180 mcg SC once weekly
• Without other anti viral drugs:
 Genotypes 1, 4: 48 weeks
 Genotypes 2, 3: 24 weeks
 Genotypes 5, 6: Insufficient data to recommend use

28. Administration
• SC. Abdomen or thigh. Rotate injection site.
• Administration should be done on the same day and at approximately the same time
each week.
Dosing
Considerations
• Only indicated for the treatment of patients with CHC with compensated liver disease if
there are contraindications or significant intolerance to other HCV antiviral drugs.
• Not recommended for treatment of patients with CHC who previously failed therapy
with an interferon-alfa.
• Not recommended for treatment of patients with CHC who have had solid organ
transplantation.
Adverse Effects Headache, Fatigue, Rigors, Insomnia, Anxiety, Alopecia, Pruritis.
Contraindications Pregnancy, Autoimmune hepatitis, Hypersensitivity, Decompensated liver disease.
Drug Interactions • may diminish the therapeutic effect of BCG (Intravesical).
• may enhance the adverse/toxic effect of CloZAPine. Agranulocytosis may be
increased.
Storage • Store in refrigerator at 2°C to 8°C. Do not freeze. Do not leave out of the refrigerator
for more than 24 hours.
• Do not shake.
• Discard any unused portion. Protect from light.

30. RIBAVIRIN
Brand Names Rebetol, Virazole, Copegus, Moderiba, Ribasphere
Pharmacokinetics
Absorption:
Bioavailability
Oral: 64%
Distribution:
Protein binding
Oral: None
Metabolism:
•Hepatically
•Intracellularly
Excretion:
•Inhalation:
Urine (40%)
•Oral capsule:
Urine (61%)
Pharmacodynamics
May inhibit the initiation and elongation of RNA fragments by inhibiting
polymerase activity, which in turn results in the inhibition of viral protein
synthesis.
Dosing forms &
strengths:
• Tablet (200mg 400mg 600mg).
• Inhalation solution (6g/vial).
• Oral solution (40mg/mL).
Indications and Dosing
C H C
(Genotype 1 to 6)
• Body weight dependent dosing. Varied.
• Period: 24 to 48 hours.

31. Administration
Oral Administer with food.
Inhalation In well ventilated rooms.
Dosing
Considerations
Dose reductions/interruptions recommended if Hgb falls.
Adverse Effects Headache, Fatigue, Fever, Rigors, Myalgia, Body pain, Back pain, Arthalagia.
Contraindications Pregnancy, Autoimmune hepatitis, Hypersensitivity, Decompensated liver disease.
Drug Interactions • Ribavirin may enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors.
Lactic acidosis may occur.
• Diminish the therapeutic effect of Influenza Virus Vaccine.
Storage • Store vials in a dry place at 15°C to 30°C.
• Store tablets at 25°C.
• Solution are refrigerated at 2°C to 8°C.

32. THROMBOPOIETIN-RECEPTOR AGONISTS

33. ELTROMBOPAG
Brand Names Promacta
Pharmacokinetics
Absorption:
Bioavailability
•Tablets: 52%
•Suspension:
increased by 22 %
Distribution:
Protein binding:
> 99%
Metabolism:
In liver
Excretion:
•In feces
•In urine
Pharmacodynamics
Interacts with transmembrane domain of human TPO receptor and induces
megakaryocyte proliferation and differentiation from bone marrow progenitor cells.
Dosing forms &
strengths
Tablet: 12.5 mg 25 mg 50 mg 75 mg
Indications and Dosing
Chronic Hepatitis C-
Associated
Thrombocytopenia
25 mg PO QD

34. Administration: Oral 1 hour before or 2 hours after a meal.
Dosing
Considerations
• Used in patients whose degree of thrombocytopenia prevents the initiation of interferon-
based therapy.
• Monitor CBCs with differentials (including platelet counts) qWeek.
• Not safe in combination with direct-acting antiviral agents.
• Used without interferons.
Adverse Effects Influenza-like symptoms, Headache, Rigor, Fatigue, Nausea, Arthralgia, Myalgia.
Contraindications Not documented.
Drug Interactions Aluminium hydroxide, Fe salts, Mg salts & calcium salts may decrease its serum
concentration.
Storage • Store oral suspension at 20°C to 25°C.
• Store oral tablets at 20°C to 25°C.

35. THANKYOU
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