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GP’s Guide to theHCV SHARED CARE

PROGRAM

KATE MELLOR. RN.HEPATOLOGY NURSE CONSULTANT

35 VICTORIA PARADEFITZROY, VICTORIA3065

PH: (03) 9288 2259FAX: (03) 9288 3596

Jan 2010

ST VINCENT’S HOSPITAL. MELBOURNE

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CONTENTS

THE INFORMATION PROVIDED IN THIS PACKAGE WILL GUIDE THE CLINICIAN THROUGH THE FOLLOWING;

Who qualifies for treatment? - SECTION 100 Pg 3

What pre-treatment test need to be done? - WORKING UP FOR TREATMENT Pg 4

The Shared Care Treatment Plan- THE TREATMENT PLAN Pg 5- THE PLAN FOR GP Pg 6

What blood test and when? - WHAT TO ORDER & WHEN Pg 9

PATTERNS OF VIROLOGICAL RESPONSE Pg 10

What do I need to look out for?- MANAGEMENT OF SIDE EFFECTS Pg 11

Who should not be treated? - CONTRAINDICATIONS Pg 14

When should I be worried? - STANDARD DOSE & DOSE REDUCTION Pg 15

Who do I contact? - CONTACTS Pg 17

THIS SHARED CARE PROTOCOL IS INTENDED TO SUPPORT CLINICIANS TREATING PATIENTS WITH HEPATITIS C

WITH PEG INTERFERON & RIBAVIRIN COMBINATION THERAPY.

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SECTION 100PATIENTS MUST FULFIL THE FOLLOWING

GOVERNMENT CRITERIA:

HCV RNA POSITIVE

18 yrs PLUS

NAÏVE PATIENT IE: NO PRIOR IFN OR PEG IFN

COMPENSATED LIVER DISEASE

BOTH PARTNERS MUST AGREE TO USE 2 FORMS OF EFFECTIVE CONTRACEPTION.

FEMALE PARTNER OR PATIENT MUST NOT BE PREGNANT

ALSO CONSIDER ACUTE HEPATITIS

Compassionate Access Scheme CIRRHOTICS WITH THROMBOCYTOPENIA

Platelets >90,000 RENAL IMPAIRMENT

Requires Ribavirin dose reduction CURRENT CLINICAL TRIALS

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WORKING UP FOR TREATMENT

Please ensure all referrals & current results are Faxed to the; Att: Hepatology NurseLiver Clinic

St Vincent’s Hospital35 Victoria Parade,Fitzroy 3065FAX: 03 9288 3596

Pre Treatment Pathology HCV PCR, Genotype + Viral Load, LFT, FBE, TFTab, SMS, Iron & Copper studies HIV & HBVab if requiredPlease ensure vaccinations for Hep A & B are up to date.

Liver Biopsy’s although not required for treatment arerecommended in some instances & can be organisedthrough the clinic.

Ultra Sound &/or Liver Biopsy - Recommended if Duration of virus longer than 20 yrs History of heavy alcohol use

Monthly LFT, FBE are required for the duration oftreatment & all results MUST be Faxed to the

Hepatology Nurse on Ph: 9288 3596

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THE TREATMENT PLANTreatment Duration:Genotypes 1, 4, & 6 48 weeks Genotypes 2 & 3 24 weeksGenotypes 2 & 3 with Cirrhosis (F3 / F4 Metavir score) are

treated for 48 weeks

Education & first injection of therapy is done at St Vincent’s Hospital, 35 Victoria Parade on the 4th Floor of theDaly Wing, by the Hepatology Nurse Ph: 9288 3580

Follow ups will be fortnightly for the first month then monthly throughout treatment for monitoring of side effects &pathology r/v.

At 3 months an assessment will be made by the specialist in clinic to determine the plan for further treatment.

Cirrhotics at risk of bone marrow suppression should be monitored every 2 months in clinic.

Non Cirrhotics can be monitored every 3 months in clinic, if psychologically stable.

Psychologically at risk should be monitored by the GP, SVHM psychiatrist & specialist along with weekly contact with the CNC.

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THE PLAN – For GP’s

At Each Review Visit

SVHM Hepatology Nurse: 03 9288 3580

Please CHECK the patients Mood swings & Sleep pattern Appetite & any Weight loss Itches and rashes Any other side effects

CHECK compliance

RE-INFORCE contraception Two effective forms

RE-INFORCE abstinence or a reduction of alcohol intake 4 standard drinks for men & 2 for women per week

PATHOLOGY R/V Haemoglobin, White cell count Neutrophils, Platelets ALT

FAX Results & Follow Up Letters to Hepatology Nurse 9288 3596

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THE PLAN – Non Cirrhotics

GP - R/V MonthlySVH - Every Two / Three Months

2 Weeks R/V with GPSide effects & pathology r/v

4 weeks R/V with Specialist & CNCside effects & pathology r/vscript & drug pick up

8 weeks R/V with GP Side effects & pathology r/v

12 weeks R/V with GPSide effects & pathology r/v

16 weeks R/V with Specialist & NurseSide effects & pathology r/v script & drug pick up

Then monthly there after until treatment has ceased. If by chance the patient becomes unwell, monthlyAppointments at SVHM would be necessary.

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THE PLAN – Cirrhotics GP- R/V Monthly

SVHM - Every Alternative Second Month.

NOTE: These patients are at risk of neutropenia &thrombocytopenia & are more likely to need dose reductions.

2 Weeks R/V with GPSide effects & pathology r/v

4 weeks R/V with Specialist & NurseSide effects & pathology r/v. Script & drug pick up

8 weeks R/V with GPSide effects & pathology r/v

12 weeks R/V with Specialist & NurseSide effects & pathology r/v script & drug pick up

16 weeks R/V with GP

Side effects & pathology r/v script & drug pick up

Then monthly there after until treatment has ceased.

If by chance the patient becomes symptomatic monthlyappointments would be necessary with the specialist.

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WHAT TO ORDER & WHEN? PLEASE FAX ALL RESULTS TO 9288 3596

GENOTYPES 2 & 3 - 24 WEEKS Week 2 LFT, FBE Week 4 LFT, FBE, HCV PCR Week 8 LFT, FBE Week 12 LFT, FBE, TFT Continue Monthly LFT, FBE End of treatment - 24 weeks LFT, FBE, TFT, HCV PCR

GENOTYPES 1,4,6 & CIRRHOTIC GENTOYPES 2 & 3 – 48 WKS Week 2 LFT, FBE Week 4 LFT, FBE, HCV PCR Week 8 LFT, FBE Week 12 LFT, FBE TFT, PCR & VL

Only continue if there has been a 2 log drop in the viral load.

Continue Monthly LFT, FBE Week 24 LFT, FBE, TFT Monthly LFT, FBE End of treatment - 48 weeks LFT, FBE TFT, PCR & VL

POST TREATMENT FOLLOW UPS 4 weeks post treatment LFT,FBE 12 weeks post treatment LFT, FBE 24 weeks post treatment LFT, FBE TFT, PCR

Please see inclosed treatment pathology flow sheet.

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6mths

Sustained Response (SVR) CURE

Breakthrough

Relapser

Partial Response

HCV RNA Undetectable

Baseline Treatment

Detection limit

Non Responder

Patterns of Virological Response

TIME

HC

V R

NA

6mths

Sustained Response (SVR) CURE

Breakthrough

Relapser

Partial Response

HCV RNA Undetectable

Baseline Treatment

Detection limit

Non Responder

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MANAGEMENT OF COMMON SIDE EFFECTS

PEG Combination Treatment can cause a range of side effects; Initial side effects

Headaches, Muscle & joint aches & pains, Fevers & chills,

The initial week is usually the worst & these common flu like symptomscan take about 6-8 weeks to subside. With 20% of patients notexperiencing side effects at all. Patient are advised to take Panadol as required & increase their fluids

Common RIBAVIRIN side effects Dry cough Dry Itchy Skin & Rashes

• No soap, moisturisers and or Chickweed Gel from health food shops.

Tiredness secondary to Anaemia• Occurs within 2 to 4 weeks of commencement of therapy • Maximum drop in the first 8 weeks• Monitor haemoglobin baseline, week 2 & then 4 weekly• Haemoglobin less than 100g/L for 2 consecutive weeks will

need dose reduction, please notify Hepatology Nurse. • Haemoglobin less than 80g/L, cease treatment

Cardiac Disease: • ECG over 50yr pre treatmentRenal Disorder: • Ribavirin is secreted through the kidneys. • Ribavirin should not be administered to patients with

creatinine clearance less than 50ml/min.

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BONE MARROW SUPPRESSION

Common Peg Interferon Side effects Hair thinning Poor appetite, weight loss Irritability, anxiety, mood swings LFT do not always normalise on Peg.

Neutropenia• Decrease in neutrophil counts are common.• Dose reduce for levels < 0.75 – notify Hepatology Nurse. • Cease if counts < 0.5 – notify Hepatology Nurse.• Neutrophils should normalise 4 weeks after stopping.

Thrombocytopenia• Platelet counts decrease in about 30-50% of the patients

on therapy. • Dose reduction of Peg IFN for counts < 50,000

• Severe thrombocytopenia 30,000 cease treatment. • Cirrhotic patients on need platelets > 90,000 • Dose reduce Cirrhotics as above.

Uncommon Peg Interferon Side effects Thyroid Abnormality

• Serious adverse events & dose modifications are rare.• Pre existing thyroid dysfunction does not preclude

combination therapy; patients will need an Endocrinology r/v prior to treatment.

• Prior to therapy patients should be tested for TFTs/ antithyroid antibodies & TFTs every 12 weeks during treatment.

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NEUROPSYCHIATRIC DISORDERS

Interferon can cause significant neuropsychiatric side effects including; depression, anxiety, impaired concentration, sleep disturbance, irritability, intolerance, fatigue, sexual dysfunction, apathy & confusion.

Mood Swings appears to be more common in people who have had similar problems in the past. We tend to see these within the first 3 months. Low dose SSRI are advised.

Clinicians should monitor; Mood swings, Sleep patterns, Weight & ask about suicidal idealisations.

If possible confirm with partner/significant other.

If concerned of an “at risk” patient contact. 1) Hepatology Nurse – 03 9288 3580 2) SVHM Specialist – 03 2988 3580

The Hepatology Nurse will arrange a referral to the psychiatrist at SVHM before treatment & if advisable during therapy.

SSRI’s are commonly prescribed which may act on the specific neurochemical targets (in particular serotonin) mediating these depressive side effects.

Most of these side effects are reversible once treatment has ceased.

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CONTRAINDICATIONS

PEG-Interferon may be contraindicated in people experiencing a

profound depression illness previous drug induced psychosis attempted suicides psychiatric illness i.e. bipolar disorders, As the treatments exacerbate this pre existing illness.

These patients require a formal psychiatric review &monitoring at the St Vincent’s Liver Clinic

Ribavirin is teratogenic, consequently combination treatment is not made available to women who are pregnant; &/or breastfeeding or thinking about planning a pregnancy; or to men whose partners are pregnant.

People undergoing treatment must agree to use two forms of effective contraception during & for six months after treatment.

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STANDARD DOSE & DOSE REDUCTION

Roche PEGASYS & RIBARVIRIN

STANDARD DOSE:

Peg IFN DOSE REDUCTIONS:

.

Laboratory values

Reduce dose if For 1 month then R/V dose again.

Discontinue if

Neutrophils <0.75 To135mcg

R/V path in 2wks

<0.5

Platelets

Cirrhotics

<50,000

<35,000

To 90mcg

R/V path in weekly 25,000

RIBAVIRIN REDUCTIONS:

Hb: <100g/L Less 200mgs til stable

<85g/L

Discontinue Ribavirin when Haemoglobin <20g/L

Genotype Pegasys Dose

(Weekly)

Ribarvirin Dose

(Daily)

NO Of 200mg Tablets

1 & 4 180mcg

(s/c injection)

<75kg = 1000mg

>75kg = 1200mg

2 morning & 3 evening

3 morning & 3 evening

2 & 3 180mcg 800mg 2 morning & 2 evening

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SCHERING-PLOUGHPEGATRON & RIBAVIRINDose & Dose Reduction

STANDARD DOSE:

PEG IFN DOSE REDUCTIONS:

RBV DOSE REDUCTIONS:

Weight

Range (kg)

40 -

46

47 - 53

54 - 60

61 - 64

65 - 72

73 -80

81 - 85

86 -90

91 - 100

Redipen per .5mL(as written on script)

100 100 100 100 120 120 150 150 150

PEG-IFN Weekly Dose (mcg)

70 80 90 100 108 120 135 135 150

INJ Volume (mL)(what patient dials up)

0.35 0.4 0.45 0.5 0.45 0.5 0.45 0.45 0.5

RBV Daily

Dose (mg)

800 800 800 800 1000 1000 1000 1200 1200

Morning

Evening

2

2

2

2

2

2

2

2

2

3

2

3

2

3

3

3

3

3

Laboratory Value Reduce dose if For 4 wks the R/V Discontinue

White Blood Cells < 1.5 To 0.35mL

on the same Strength Redipen

r/v pathology in

2 wks.

1.0

Neutrophils < 0.75 0.5

Platelets < 50,000 25

Haemoglobin < 100 g/L 600mg <85 g/L

Haemoglobin

(In Pts with stable Cardiac Disease)

> 20 g/L Decrease in Hb during any 4 week period of treatment results in a permanent

dose reduction of .

<120 g/L

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CONTACTS

Kate MellorHepatology Nurse ConsultantGastroenterology DepartmentLevel 4 Daly Wing 35 Victoria Parade Fitzroy 3065.

katherine.mellor@svhm.org.auPh:03 9288 2259Mob: 0407 511 299Fax: 03 9288 3596

SVHM Specialist can be contacted through the

Gastroenterology Department. Address as abovePh: 03 9288 3580 Fax: 03 9288 3590

• Marianne CroweHepatology Nurse ConsultantGastroenterology DepartmentLevel 4 Daly Wing 35 Victoria Parade Fitzroy 3065.

marianne.crowe@svhm.org.auPh:03 9288 3597Fax: 03 9288 3596

Lai-Me Lam Out Patient Pharmacist SVHMPh: 03 9288 3462 Fax: 03 9288 4174