Cytomegalovirus infection INOSINE PRANOBEX U

5.3.2.2 Cytomegalovirus infection INOSINE PRANOBEX U

(Inosine acedoben dimepranol) Recommendations for the optimum maintenance ther- apy of cytomegalovirus (CMV) infections and the dura-

Indications see under Dose tion of treatment are subject to rapid change. Cautions renal impairment (Appendix 3); history of

Ganciclovir is related to aciclovir but it is more active gout or hyperuricaemia

against cytomegalovirus; it is also much more toxic than Contra-indications pregnancy

aciclovir and should therefore be prescribed only when

5.3.2 Herpesvirus infections BNF 57 the potential benefit outweighs the risks. Ganciclovir is

. Maintenance treatment, beginning 2 weeks after administered by intravenous infusion for the initial treat-

completion of induction, ADULT over 18 years, by ment of CMV infection. Ganciclovir causes profound

intravenous infusion over 1 hour, 5 mg/kg once myelosuppression when given with zidovudine; the two

every 2 weeks (give probenecid and intravenous should not normally be given together particularly dur-

fluids with each dose, see below) ing initial ganciclovir therapy. The likelihood of ganci-

Probenecid co-treatment By mouth (preferably after food), clovir resistance increases in patients with a high viral

probenecid 2 g 3 hours before cidofovir infusion followed by load or in those who receive the drug over a long

probenecid 1 g at 2 hours and 1 g at 8 hours after the end of duration; cross-resistance to cidofovir is common.

cidofovir infusion (total probenecid 4 g); for cautions, contra- indications and side-effects of probenecid see section 10.1.4

Valaciclovir (see p. 345) is licensed for prevention of Prior hydration Sodium chloride 0.9%, by intravenous cytomegalovirus disease following renal transplanta-

infusion , 1 litre over 1 hour immediately before cidofovir tion.

infusion (if tolerated an additional 1 litre may be given over 1–3 hours, starting at the same time as the cidofovir infusion

Valganciclovir is an ester of ganciclovir which is or immediately afterwards) licensed for the initial treatment and maintenance treat-

ment of CMV retinitis in AIDS patients. Valganciclovir is Vistide (Pfizer) A

, cidofovir 75 mg/mL, net price also licensed for preventing CMV disease following

Intravenous infusion 5-mL vial = £653.22

solid organ transplantation from a cytomegalovirus- Caution in handling positive donor. Cidofovir is toxic and personnel should be adequately protected during handling and administration; if

Foscarnet is also active against cytomegalovirus; it is solution comes into contact with skin or mucosa, wash off immediately with water

toxic and can cause renal impairment. Cidofovir is given in combination with probenecid for

CMV retinitis in AIDS patients when ganciclovir and foscarnet are contra-indicated. Cidofovir is nephrotoxic.

GANCICLOVIR

For local treatment of CMV retinitis, see section 11.3.3. Indications life-threatening or sight-threatening cyto- megalovirus infections in immunocompromised

ns

patients only; prevention of cytomegalovirus disease during immunosuppressive therapy following organ

transplantation; local treatment of CMV retinitis Infectio Indications cytomegalovirus retinitis in AIDS patients

CIDOFOVIR

(section 11.3.3)

Cautions 5 close monitoring of full blood count (severe for whom other drugs are inappropriate Cautions monitor renal function (serum creatinine and

deterioration may require correction and possibly urinary protein) and neutrophil count within 24 hours

treatment interruption); history of cytopenia; low before each dose; co-treatment with probenecid and

platelet count; potential carcinogen and teratogen; prior hydration with intravenous fluids necessary to

renal impairment (Appendix 3); radiotherapy; ensure minimise potential nephrotoxicity (see below); dia-

adequate hydration during intravenous administra- betes mellitus (increased risk of ocular hypotony);

tion; vesicant—infuse into vein with adequate flow interactions: Appendix 1 (cidofovir)

preferably using plastic cannula; children (possible Nephrotoxicity Do not initiate treatment in renal impair-

risk of long-term carcinogenic or reproductive toxi- ment (assess creatinine clearance and proteinuria—consult

city—not for neonatal or congenital cytomegalovirus product literature); discontinue treatment and give intra-

disease); interactions: Appendix 1 (ganciclovir) venous fluids if renal function deteriorates—consult product

Contra-indications pregnancy (ensure effective literature Ocular disorders Regular ophthalmological examinations

contraception during treatment and barrier contra- recommended; iritis and uveitis have been reported which

ception for men during and for at least 90 days after may respond to a topical corticosteroid with or without a

treatment; Appendix 4); breast-feeding; hypersensi- cycloplegic drug—discontinue cidofovir if no response to

tivity to ganciclovir or aciclovir; abnormally low hae- topical corticosteroid or if condition worsens, or if iritis or

moglobin, neutrophil, or platelet counts (consult pro- uveitis recurs after successful treatment Contra-indications

duct literature)

renal impairment (creatinine Side-effects diarrhoea, nausea, vomiting, dyspepsia, clearance 55 mL/minute or less); concomitant

abdominal pain, constipation, flatulence, dysphagia, administration of potentially nephrotoxic drugs (dis-

hepatic dysfunction; dyspnoea, chest pain, cough; continue potentially nephrotoxic drugs at least 7 days

headache, insomnia, convulsions, dizziness, neuro- before starting cidofovir); pregnancy (avoid

pathy, depression, anxiety, confusion, abnormal pregnancy during and for 1 month after treatment, men should not father a child during or within 3

thinking, fatigue, weight loss, anorexia; infection, months of treatment; Appendix 4), breast-feeding

fever, night sweats; anaemia, leucopenia, thrombo- (Appendix 5)

cytopenia, pancytopenia, renal impairment; myalgia, Side-effects

arthralgia; macular oedema, retinal detachment, vitr- nephrotoxicity (see Cautions above);

eous floaters, eye pain; ear pain, taste disturbance; nausea, vomiting; dyspnoea; headache, fever, asthe-

dermatitis, pruritus; injection-site reactions; less com- nia; neutropenia; decreased intra-ocular pressure, iri-

monly mouth ulcers, pancreatitis, arrhythmias, hypo- tis, uveitis (see Cautions above); alopecia, rash; less

tension, anaphylactic reactions, psychosis, tremor, commonly Fanconi syndrome; also reported, hearing

male infertility, haematuria, disturbances in hearing impairment and pancreatitis

and vision, and alopecia Dose

Dose

. Initial (induction) treatment, ADULT over 18 years, by . By intravenous infusion , initially (induction) 5 mg/ intravenous infusion over 1 hour, 5 mg/kg once

kg every 12 hours for 14–21 days for treatment or for weekly for 2 weeks (give probenecid and intra-

7–14 days for prevention; maintenance (for patients venous fluids with each dose, see below)

at risk of relapse of retinitis) 6 mg/kg daily on

BNF 57

5.3.3 Viral hepatitis 347

5 days per week or 5 mg/kg daily until adequate

Dose

recovery of immunity; if retinitis progresses initial . CMV retinitis, induction, 900 mg twice daily for 21 induction treatment may be repeated

days then 900 mg once daily; induction regimen may Cymevene c (Roche)

A be repeated if retinitis progresses

Intravenous infusion , powder for reconstitution, . Prevention of cytomegalovirus disease following solid ganciclovir (as sodium salt). Net price 500-mg vial =

organ transplantation (starting within 10 days of £31.60

transplantation), 900 mg once daily for 100 days

Electrolytes Na 2 mmol/500-mg vial

. CHILD under 18 years not recommended Caution in handling Ganciclovir is toxic and personnel should be

Note Oral valganciclovir 900 mg twice daily is equivalent to adequately protected during handling and administration; if

intravenous ganciclovir 5 mg/kg twice daily solution comes into contact with skin or mucosa, wash off immediately with soap and water

Valcyte c (Roche) A Tablets , pink, f/c, valganciclovir (as hydrochloride) 450 mg, net price 60-tab pack = £1148.05. Label: 21

FOSCARNET SODIUM

Caution in handling Valganciclovir is a potential teratogen and carcinogen and caution is advised for handling of broken

Indications cytomegalovirus retinitis in AIDS tablets; if broken tablets come into contact with skin or patients; mucocutaneous herpes simplex virus infec-

mucosa, wash off immediately with water tions unresponsive to aciclovir in immunocompro-

mised patients Cautions renal impairment (reduce dose; consult product literature); monitor electrolytes, particularly calcium and magnesium; monitor serum creatinine

5.3.3 Viral hepatitis

every second day during induction and every week during maintenance; ensure adequate hydration;

Treatment for viral hepatitis should be initiated by a avoid rapid infusion; interactions: Appendix 1 (fos-

specialist. The management of uncomplicated acute carnet)

viral hepatitis is largely symptomatic. Early treatment Contra-indications pregnancy; breast-feeding

of acute hepatitis C with interferon alfa [unlicensed (Appendix 5)

indication] may reduce the risk of chronic infection. Side-effects

Hepatitis B and hepatitis C viruses are major causes nausea, vomiting, diarrhoea (occasion-

of chronic hepatitis. For details on immunisation against ally constipation and dyspepsia), abdominal pain,

hepatitis A and B infections, see section 14.4 (active anorexia; changes in blood pressure and ECG; head-

immunisation) and section 14.5 (passive immunisation). ache, fatigue, mood disturbances (including psycho-

sis), asthenia, paraesthesia, convulsions, tremor, diz- Chronic Hepatitis B Peginterferon alfa-2a (section ziness, and other neurological disorders; rash; Infections impairment of renal function including acute renal

8.2.4) is an option for the initial treatment of chronic failure; hypocalcaemia (sometimes symptomatic) and

hepatitis B (see NICE guidance below) and may be other electrolyte disturbances; abnormal liver func-

preferable to interferon alfa. The use of peginterferon tion tests; decreased haemoglobin concentration,

alfa-2a and interferon alfa is limited by a response rate of leucopenia, granulocytopenia, thrombocytopenia;

30–40% and relapse is frequent. Treatment should be thrombophlebitis if given undiluted by peripheral vein;

discontinued if no improvement occurs after 4 months. genital irritation and ulceration (due to high concen-

The manufacturers of peginterferon alfa-2a and inter- trations excreted in urine); isolated reports of pan-

feron alfa contraindicate use in decompensated liver creatitis

disease but low doses can be used with great caution Dose

in these patients. Although interferon alfa is contra- indicated in patients receiving immunosuppressant

. CMV retinitis, by intravenous infusion , induction treatment (or who have received it recently), cautious

60 mg/kg every 8 hours for 2–3 weeks then main- use of peginterferon alfa-2a may be justified in some tenance, 60 mg/kg daily, increased to 90–120 mg/

cases.

kg if tolerated; if retinitis progresses on maintenance dose, repeat induction regimen

Adefovir dipivoxil, entecavir, lamivudine (see p. 337), telbivudine, or tenofovir disoproxil (see p. 338) are

. Mucocutaneous herpes simplex infection, by intra- venous infusion licensed for the treatment of chronic hepatitis B. Lami- , 40 mg/kg every 8 hours for 2–3 weeks or until lesions heal vudine or adefovir can also be used in patients with

decompensated liver disease. Hepatitis B viruses with Foscavir c (AstraZeneca) A reduced susceptibility to lamivudine have emerged fol-

Intravenous infusion , foscarnet sodium hexahydrate lowing extended therapy. Adefovir is effective in lami-

24 mg/mL, net price 250-mL bottle = £34.49 vudine-resistant chronic hepatitis B but telbivudine should not be used because cross-resistance may occur (see also NICE guidance below). Entecavir is

effective in patients not previously treated with nucleo- Note Valganciclovir is a pro-drug of ganciclovir

VALGANCICLOVIR

side analogues (see NICE guidance below). Resistance to entecavir can occur in patients who have received

Indications induction and maintenance treatment of

lamivudine.

cytomegalovirus retinitis in AIDS patients; prevention If there is no toxicity or loss in efficacy, treatment with of cytomegalovirus disease following solid organ

adefovir, entecavir, lamivudine, telbivudine, or tenofovir transplantation from a cytomegalovirus-positive

is usually continued until 6 months after adequate donor. Cautions

seroconversion has occurred. Treatment with lamivu- see under Ganciclovir

dine or adefovir is continued long-term in patients with Side-effects see under Ganciclovir

decompensated liver disease.

5.3.3 Viral hepatitis BNF 57 Tenofovir, or a combination of tenofovir with either

emtricitabine or lamivudine may be used with other

NICE guidance

antiretrovirals, as part of ‘highly active antiretroviral Peginterferon alfa, interferon alfa, and therapy’ (section 5.3.1) in patients who require treat-

ribavirin for moderate to severe chronic ment for both HIV and chronic hepatitis B. If patients

hepatitis C (January 2004) infected with both HIV and chronic hepatitis B only

The combination of peginterferon alfa and ribavirin require treatment for chronic hepatitis B, they should

should be used for treating moderate to severe receive antivirals that are not active against HIV, such as

chronic hepatitis C in patients aged over 18 years: peginterferon alfa-2a. Management of these patients

not previously treated with interferon alfa or should be co-ordinated between HIV and hepatology

peginterferon alfa; specialists.

treated previously with interferon alfa alone or in combination with ribavirin;

NICE guidance

whose condition did not respond to peginterfer- Adefovir dipivoxil and peginterferon alfa-2a

on alfa alone or responded but subsequently for chronic hepatitis B (February 2006)

relapsed.

Peginterferon alfa-2a is an option for the initial Peginterferon alfa alone should be used if ribavirin is treatment of chronic hepatitis B.

contra-indicated or not tolerated. Interferon alfa for Adefovir dipivoxil is recommended as an option for

either monotherapy or combined therapy should be the treatment of chronic hepatitis B if:

used only if neutropenia and thrombocytopenia are .

treatment with interferon alfa or peginterferon

a particular risk. Patients receiving interferon alfa alfa-2a has been unsuccessful, or

may be switched to peginterferon alfa. .

a relapse occurs after successful initial therapy, Full guidance available at www.nice.org.uk/TA075 . or .

treatment with interferon alfa or peginterferon alfa-2a is poorly tolerated or contra-indicated.

ADEFOVIR DIPIVOXIL

Adefovir dipivoxil should not be given before treat- Indications ns chronic hepatitis B infection with either ment with lamivudine. It may be used either alone or in combination with lamivudine when treatment

compensated liver disease with evidence of viral with lamivudine has resulted in viral resistance, or

replication, and histologically documented active liver if lamivudine resistance is likely to occur rapidly and

inflammation and fibrosis or decompensated liver

Infectio

adversely affect the outcome.

disease