Valganciclovir Mylan

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Valganciclovir hydrochloride 496.3 mg equivalent to valganciclovir 450 mg
Available from:
Viatris Limited
INN (International Name):
Valganciclovir hydrochloride 496.3 mg (= valganciclovir 450 mg)
Dosage:
450 mg
Pharmaceutical form:
Film coated tablet
Composition:
Active: Valganciclovir hydrochloride 496.3 mg equivalent to valganciclovir 450 mg Excipient: Crospovidone Microcrystalline cellulose Opadry brown 15B565009 Purified water Stearic acid
Prescription type:
Prescription
Manufactured by:
Mylan Laboratories Limited
Therapeutic indications:
For the treatment of cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS) patients. For the prevention of CMV disease in solid organ transplant patients at risk.
Product summary:
Package - Contents - Shelf Life: Bottle, HDPE white bottle with white opaque polypropylene cap with Al induction sealing wad - 60 tablets - 24 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-9410
Authorization date:
2013-10-10

Read the complete document

Page 1 of 4

NEW ZEALAND CONSUMER MEDICINE INFORMATION

VALGANCICLOVIR MYLAN

Valganciclovir film coated tablet 450 mg

What is in this leaflet

Please read this leaflet carefully

before you start taking

Valganciclovir Mylan.

This leaflet answers some common

questions about Valganciclovir

Mylan.

It does not contain all the available

information. It does not take the

place of talking to your doctor or

pharmacist.

All medicines have risks and

benefits. Your doctor has weighed

the risks of you taking

Valganciclovir Mylan against the

benefits they expect it will have for

you.

If you have any concerns about

taking this medicine, ask your

doctor or pharmacist.

Keep this leaflet with the

medicine. You may need to read it

again.

What Valganciclovir

Mylan is used for

Valganciclovir Mylan is used to treat

CMV eye infections (known as CMV

retinitis) in AIDS patients, which, if

left untreated can cause blindness.

It is not a cure for CMV eye

infections.

Valganciclovir Mylan is not effective

against any underlying HIV

infection.

Valganciclovir Mylan is also used to

prevent CMV infection in patients

following organ transplantation.

Valganciclovir Mylan contains the

active ingredient valganciclovir. It

belongs to a group of medicines

used to prevent the growth of

viruses.

Valganciclovir Mylan acts against a

virus called cytomegalovirus or

CMV (a type of herpes virus). It

prevents this virus from growing and

multiplying in the body. CMV

causes infections, mainly in people

with poor immunity. Poor immunity

can be caused by HIV/ AIDS or by

medications taken after an organ

transplant.

Your doctor may have prescribed

this medicine for another reason.

Ask your doctor if you have any

questions about why this

medicine has been prescribed for

you.

Valganciclovir Mylan is not

addictive.

This medicine is available only with

a doctor’s prescription.

Before you take

Valganciclovir Mylan

Animal and other laboratory studies

have shown valganciclovir causes

infertility, birth defects and cancer. It

is possible that these effects may

also occur in humans.

When you must not take

it

Do not take Valganciclovir Mylan

if you have an allergy to:

any medicine containing

valganciclovir

any other similar medicine

such as ganciclovir,

valaciclovir, aciclovir

any of the ingredients listed

at the end of this leaflet.

Some of the symptoms of an

allergic reaction may include:

shortness of breath; wheezing or

difficulty breathing; swelling of the

face, lips, tongue or other parts of

the body; rash, itching or hives on

the skin.

Do not take Valganciclovir Mylan

if you have very low blood counts

or platelets (which help with

clotting), neutrophils (a type of

white blood cell which defends

against infection) or low

haemoglobin (oxygen carrying

substance in the blood).

Do not take this medicine after

the expiry date printed on the

pack or if the packaging is torn or

shows signs of tampering.

If it has expired or is damaged,

return it to your pharmacist for

disposal.

If you are not sure whether you

should start taking this medicine,

talk to your doctor.

Use in children

There is limited information on the

safe and effective use of

valganciclovir in children. Your

doctor will advise you whether

Valganciclovir Mylan is suitable for

your child.

Before you start to take

it

Tell your doctor if you have

allergies to any other medicines,

foods, preservatives or dyes.

Tell your doctor if you have or

have had any of the following

medical conditions:

a history of low blood

counts for platelets

(thrombocytopenia),

neutrophils (neutropenia) or

anaemia

poor kidney function

poor liver function.

Tell your doctor if you are

pregnant or plan to become

pregnant.

Valganciclovir Mylan is not

recommended for use during

pregnancy. It may affect your

developing baby if you take it during

pregnancy. Your doctor will discuss

Page 2 of 4

the risks and benefits of using

Valganciclovir Mylan if you are

pregnant.

Tell your doctor if you are breast-

feeding or intend to breast-feed.

It is not known whether

valganciclovir passes into breast

milk. Breast feeding is not

recommended during treatment with

Valganciclovir Mylan.

Tell your doctor if you are a

woman who could become

pregnant and you are not using

contraception.

You must use a reliable form of

contraception during Valganciclovir

Mylan therapy, and for at least 30

days after stopping Valganciclovir

Mylan, unless you are not sexually

active.

Tell your doctor if you are a

sexually active man.

You should use condoms while you

are taking Valganciclovir Mylan and

for a further 90 days after you have

stopped taking it. Valganciclovir

Mylan may affect the production of

sperm. Your doctor will discuss the

risks and benefits of using this

medicine.

If you have not told your doctor

about any of the above, tell them

before you start taking

Valganciclovir Mylan.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including medicines

that you buy without a

prescription from your pharmacy,

supermarket or health food shop.

You should also tell any health

professional who is prescribing a

new medication for you that you are

taking Valganciclovir Mylan.

Some medicines may interfere with

Valganciclovir Mylan. These

include:

imipenem/cilastatin (a

combination medicine used

to treat some infections)

probenecid, a medicine

used to treat gout

zidovudine, didanosine,

stavudine, also known as

D4T – medicines used for

people with HIV infection

medicines used to prevent

rejection after a transplant,

such as mycophenolate

mofetil, ciclosporin,

tacrolimus

medicines used for the

treatment of cancer such as

vincristine, vinblastine,

doxorubicin, hydroxyurea

anti-infective agents such

as trimethoprim,

sulphonamides, dapsone,

pentamidine, flucytosine,

pegylated interferons and

amphotericin B.

These medicines may be affected

by Valganciclovir Mylan or may

affect how well it works. You may

need different amounts of your

medicine, or you may need to take

different medicines.

Your doctor and pharmacist have

more information on medicines to

be careful with or avoid while taking

this medicine.

Ask your doctor or pharmacist if

you are not sure about this list of

medicines.

How to take

Valganciclovir Mylan

Follow all directions given to you

by your doctor or pharmacist

carefully.

They may differ from the information

contained in this leaflet.

If you do not understand the

instructions on the bottle, ask

your doctor or pharmacist for

help.

How much to take

Take Valganciclovir Mylan

exactly as your doctor has

prescribed.

Your doctor will tell you how many

Valganciclovir Mylan tablets to take

each day.

Treatment of CMV retinitis in

AIDS

The usual starting dose (initial

treatment) is two 450 mg tablets

twice a day with food (a total of

4 tablets per day) for 21 days.

The usual maintenance dose, or

dose for people with inactive CMV

retinitis is two 450 mg tablets once

a day with food.

Prevention of CMV disease in

transplantation

The usual dose is 900 mg (two

450 mg tablets) once daily with

food, starting within 10 days of your

organ transplant and continuing

until 100 days after the transplant.

If you have received a kidney

transplant, the same daily dose is

required and continues until

200 days after the transplant.

Your dose may have to be reduced

or stopped if you have or develop

low blood counts, have kidney

disease, or if you are older than

65 years.

How to take it

Swallow the tablets whole with a

full glass of water. Valganciclovir

Mylan must be taken with food.

If you are unable to eat for any

reason, you should still take the

tablets when they are due.

When to take it

Take Valganciclovir Mylan during

or immediately after a meal.

If you take this medicine on an

empty stomach, it may not work as

well.

Take your medicine at about the

same time each day.

Taking it at the same time each day

will have the best effect. It will also

help you remember when to take it.

How long to take it

Continue taking Valganciclovir

Mylan until your doctor tells you

to stop.

If you forget to take it

If it is almost time for your next

dose, skip the dose you missed

and take your next dose when

you are meant to.

Otherwise, take it as soon as you

remember, and then go back to

taking your medicine as you

would normally.

Page 3 of 4

Do not take a double dose to

make up for the dose that you

missed.

If you are not sure what to do,

ask your doctor or pharmacist.

If you have trouble remembering to

take your medicine, ask your

pharmacist for some hints.

While you are taking

Valganciclovir Mylan

Things you must do

Tell all doctors, dentists, and

pharmacists who treat you that

you are taking Valganciclovir

Mylan.

If either you or your partner

becomes pregnant while taking

Valganciclovir Mylan, tell your

doctor immediately.

It is extremely important that

both men and women of child-

bearing age use effective

contraception during treatment

with Valganciclovir Mylan.

If you need advice on contraception,

ask your doctor before you start

taking Valganciclovir Mylan.

Men should use condoms while

taking Valganciclovir Mylan and

should continue to use condoms for

90 days after treatment has

finished. Women should use

effective contraception during and

for 30 days after treatment has

finished.

See your doctor regularly so that

your CMV disease, blood counts

and any other potential side

effects may be monitored

carefully.

If blood cell counts are low then this

may reduce your ability to fight

infection, or for your blood to clot

efficiently. If left undetected these

effects may contribute to death or

serious illness.

If you have an CMV eye infection,

you must also see your doctor

regularly to monitor the condition of

your retina (part of your eye).

Tell your doctor if, for any

reason, you have not taken your

medicine exactly as prescribed.

Otherwise, your doctor may think

that it was not effective and change

your treatment unnecessarily.

Tell your doctor if you feel the

tablets are not helping your

condition.

Keep all of your appointments

with your doctor so that your

progress can be checked.

Things you must not do

Do not take Valganciclovir Mylan

to treat any other complaints

unless your doctor tells you to.

Do not give your medicine to

anyone else, even if they have

the same condition as you.

Do not stop taking Valganciclovir

Mylan or change the dosage

without checking with your

doctor.

Do not let yourself run out of

medicine over the weekend or on

holidays.

Do not take any other medicines

whether they require a

prescription or not without first

telling your doctor or consulting

a pharmacist.

Things to be careful of

Be careful when handling

Valganciclovir Mylan tablets.

Do not break or crush them. If

you accidentally touch broken or

crushed tablets, wash your

hands thoroughly with soap and

water. If any powder from the

tablet gets in your eyes, rinse

your eyes thoroughly with water.

Be careful driving or operating

machinery until you know how

Valganciclovir Mylan affects you.

This medicine may cause dizziness,

confusion or seizures (fits) in some

people and therefore may affect

alertness. If you have any of these

symptoms, do not drive, operate

machinery or do anything else that

could be dangerous.

In case of overdose

If you take too much

(overdose)

Immediately telephone your

doctor or the National Poisons

Centre (telephone 0800 POISON

or 0800 764 766) or go to accident

and emergency at your nearest

hospital, if you think that you or

anyone else may have taken too

much Valganciclovir Mylan. Do

this even if there are no signs of

discomfort or poisoning. You may

need urgent medical attention.

Symptoms of an overdose may

include abdominal pain, diarrhoea,

vomiting, convulsion (fit), swelling

ankles and shortness of breath.

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not

feel well while you are taking

Valganciclovir Mylan.

This medicine helps most people

with CMV infections, but it may

have unwanted side effects in a few

people.

All medicines can have side

effects. Sometimes they are

serious, most of the time they are

not. You may need medical

treatment if you get some of the

side effects.

Ask your doctor or pharmacist to

answer any questions you may

have.

Tell your doctor if you notice any

of the following and they worry

you:

looking pale and/or

dizziness (anaemia)

diarrhoea or constipation

feeling sick (nausea) or

vomiting

fever

headache

indigestion

tingling or numbness of the

hands and feet

shaking or tremors

runny nose, sore throat or

nasal passages

loss of appetite, weight loss

painful, swollen joints,

muscle pain

pain when passing urine.

These are the more common side

effects of Valganciclovir Mylan.

Page 4 of 4

Tell your doctor immediately if

you notice any of the following:

skin rash (dermatitis)

abdominal pain

cough

tiredness (fatigue)

sore, creamy yellow raised

patches in the mouth (oral

thrush)

unable to sleep (insomnia)

worsening of your eyesight.

These side effects may be serious.

You may require medical attention.

If any of the following happen,

tell your doctor immediately or

go to Accident and Emergency at

your nearest hospital:

swelling of the tongue, lips

or throat

wheezing or difficulty

breathing

any sign of infection such

as fever, chills, sore throat

or mouth ulcers

unexplained bruising or

bleeding

abnormal thoughts,

confusion, agitation,

hallucinations (seeing,

hearing or feeling things

that are not there)

convulsions (fits)

problems with your eyesight

such as seeing bright

flashes of light.

The above list includes very serious

side effects. You may need urgent

medical attention or hospitalisation.

Tell your doctor or pharmacist if

you notice anything that is

making you feel unwell.

Other side effects not listed above

may also occur in some people. Tell

your doctor if you notice any other

effects.

Do not be alarmed by this list of

possible side effects. You may

not experience any of them.

After taking

Valganciclovir Mylan

Storage

Keep your tablets in the bottle

until it is time to take them.

If you take the tablets out of the

bottle they may not keep well.

Keep your tablets in a cool dry

place where the temperature

stays below 25°C.

Do not store Valganciclovir Mylan or

any other medicine in the bathroom

or near a sink. Do not leave it on a

window sill or in the car.

Heat and dampness can destroy

some medicines.

Keep it where children cannot

reach it.

A locked cupboard at least one-and-

a half metres above the ground is a

good place to store medicines.

Disposal

If your doctor tells you to stop

taking this medicine or the expiry

date has passed, ask your

pharmacist what to do with any

medicine that is left over.

Product description

What it looks like

Valganciclovir Mylan are pink film-

coated, oval, biconvex, bevelled

edge tablets marked with "M" on

one side of the tablet and "V45" on

the other side.

Ingredients

Active ingredient(s):

Valganciclovir Mylan contains

450 mg of valganciclovir as the

active ingredient.

Inactive ingredient(s):

Valganciclovir Mylan also contains:

microcrystalline cellulose

crospovidone

stearic acid

hypromellose

titanium dioxide

macrogol

iron oxide red

polysorbate.

This medicine does not contain

lactose or gluten.

If you want to know

more

Should you have any questions

regarding this product, please

contact your pharmacist or doctor.

Who supplies this

medicine

Valganciclovir Mylan is supplied in

New Zealand by:

Mylan New Zealand Ltd,

PO Box 11183,

Ellerslie,

Auckland

NEW ZEALAND

Telephone: (09) 579 2792

Date of Preparation

5 February 2019

(Based on datasheet dated 4

February 2019)

Read the complete document

Page 1 of 20

NEW ZEALAND DATA SHEET

VALGANCICLOVIR MYLAN

1. Product Name

Valganciclovir Mylan 450 mg film-coated tablet.

2. Qualitative and Quantitative Composition

Each film-coated tablet contains 496.3 mg of valganciclovir hydrochloride equivalent to 450 mg of

valganciclovir.

For the full list of excipients, see section 6.1.

3. Pharmaceutical Form

A pink film-coated, oval, biconvex, beveled edge tablet debossed with “M” on one side of the tablet

and “V45” on the other side.

4. Clinical Particulars

4.1

Therapeutic indications

Valganciclovir Mylan is indicated for the treatment of cytomegalovirus (CMV) retinitis in acquired

immunodeficiency syndrome (AIDS) patients.

Valganciclovir Mylan Is indicated for the prevention of CMV disease in solid organ transplant patients

at risk.

4.2

Dose and method of administration

Caution – Strict adherence to dosage recommendations is essential to avoid overdose.

Standard dosage

Valganciclovir Mylan is administered orally and should be taken with food (see section 5.1).

Valganciclovir Mylan is rapidly and extensively converted into the active ingredient ganciclovir. The

bioavailability of ganciclovir from valganciclovir is up to 10-fold higher than from oral ganciclovir.

The dosage and administration of Valganciclovir Mylan tablets as described below should be closely

followed (see section 4.4).

Treatment of cytomegalovirus (CMV) retinitis

Adult patients

Induction treatment of CMV retinitis

For patients with CMV retinitis, the recommended dose is 900 mg (two 450 mg tablets) with food

twice a day for 21 days. Prolonged induction treatment may increase the risk of bone marrow toxicity

(see section 4.4).

Page 2 of 20

Maintenance treatment of CMV retinitis

Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is

900 mg (two 450 mg tablets) with food once daily. Patients whose retinitis worsens may repeat

induction treatment.

The duration of maintenance treatment should be determined on an individual basis.

Prevention of CMV disease in transplantation

For kidney transplant patients, the recommended dose is 900 mg (two 450 mg tablets) once daily

with

food,

starting

within

days

post-transplantation

continuing

until

days

post-transplantation.

For patients who have received a solid organ transplant other than kidney, the recommended dose

is 900 mg (two 450 mg tablets) once daily with food, starting within 10 days post-transplantation and

continuing until 100 days post-transplantation.

Special dosage instructions

Patients with renal impairment

Adult patients

Serum creatinine or creatinine clearance levels should be monitored carefully. Dosage adjustment

is required according to creatinine clearance as shown in the table below (see sections 5.2 and 4.4).

CrCl (mL/min)

Induction dose

Maintenance / Prevention dose

900 mg twice daily

900 mg once daily

40 - 59

450 mg twice daily

450 mg once daily

25 - 39

450 mg once daily

450 mg every 2 days

10 - 24

450 mg every 2 days

450 mg twice weekly

An estimated creatinine clearance can be related to serum creatinine by the following formulae:

For males:

(140 – age [years]) x (body weight [kg])

(72) x (0.011 x serum creatinine [micromol/L])

For females:

0.85 x male value

Patients undergoing haemodialysis

For patients on haemodialysis (CrCl < 10 mL/min) a dose recommendation cannot be given. Thus,

Valganciclovir Mylan should not be used in these patients (see sections 5.2 and 4.4).

Elderly

Safety and efficacy have not been established in this patient population. No studies have been

conducted in adults older than 65 years of age. Since renal clearance decreases with age,

valganciclovir should be administered to elderly patients with special consideration of their renal

status (see section 4.4).

Hepatic impairment

The safety and efficacy of valganciclovir have not been established in patients with hepatic

impairment (see sections 5.1 and 4.4)

Page 3 of 20

Paediatric patients

See sections 4.8 and 5.1 for information on paediatric use.

4.3

Contraindications

Valganciclovir Mylan is contraindicated in patients with known hypersensitivity to valganciclovir,

ganciclovir or to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use

Cross hypersensitivity

Due to the similarity of the chemical structure of valganciclovir and that of aciclovir and penciclovir,

a cross-hypersensitivity reaction between these medicines is possible. Caution should therefore be

used when prescribing valganciclovir to patients with known hypersensitivity to acyclovir or

penciclovir, (or to their prodrugs, valaciclovir or famciclovir respectively).

Mutagenicity, teratogenicity, carcinogenicity, fertility and contraception

In animal studies ganciclovir was found to be mutagenic, teratogenic, carcinogenic and to impair

fertility. Valganciclovir should therefore be considered a potential teratogen and carcinogen in

humans with the potential to cause birth defects and cancers (see section 6.6). Prior to initiation of

ganciclovir treatment, patients should be advised of the potential risks to the foetus and to use

contraceptive measures (see section 4.6). Based on clinical and nonclinical studies, valganciclovir

may cause temporary or permanent inhibition of spermatogenesis (see sections 5.3 and 4.8).

Myelosuppression

Valganciclovir should be used with caution in patients with pre-existing haematological cytopenia or

a history of drug-related haematological cytopenia and in patients receiving radiotherapy.

Severe

leucopenia,

neutropenia,

anaemia,

thrombocytopenia,

pancytopenia,

bone

marrow

depression and aplastic anaemia have been observed in patients treated with valganciclovir (and

ganciclovir).

Therapy

should

initiated

absolute

neutrophil

count

less

than

500 cells/microlitre or the platelet count is less than 25,000/microlitre or the haemoglobin is less than

8 g/dL (see sections 4.2 and 4.8).

It is recommended that complete blood counts and platelet counts be monitored in all patients during

therapy, particularly in patients with renal impairment and in neonates and infants.

In patients with severe leucopenia, neutropenia, anaemia and/or thrombocytopenia, treatment with

haematopoietic growth factors and/or the interruption of therapy is recommended (see section 4.8).

In patients with impaired renal function, dosage adjustments based on creatinine clearance are

required (see sections 4.2 and 5.2).

For patients on haemodialysis (CrCl < 10 mL/min) a dose recommendation cannot be given. Thus,

valganciclovir should not be used in these patients (see sections 4.2 and 5.2).

Use with other medicines

Seizures have been reported in patients taking imipenem-cilastatin and ganciclovir. Valganciclovir

should not be used concomitantly with imipenem-cilastatin unless the potential benefits outweigh the

potential risks (see section 4.5).

Zidovudine and valganciclovir each have the potential to cause neutropenia and anaemia. Some

patients may not tolerate concomitant therapy at full dosage (see section 4.5).

Didanosine plasma concentrations may increase during concomitant use with valganciclovir;

therefore, patients should be closely monitored for didanosine toxicity (see section 4.5).

Page 4 of 20

Concomitant use of other medicines that are known to be myelosuppressive or associated with renal

impairment with valganciclovir may result in added toxicity (see section 4.5).

4.5

Interaction with other medicines and other forms of interaction

Valganciclovir is the pro-drug of ganciclovir; therefore, interactions associated with ganciclovir are

expected.

Imipenem-cilastatin

Convulsions have been reported in patients taking ganciclovir and imipenem-cilastatin concomitantly

and a pharmacodynamic interaction between these two drugs cannot be discounted. These

medicines should not be used concomitantly unless the potential benefits outweigh the potential

risks (see section 4.4).

Potential medicine interactions

Toxicity may be enhanced when ganciclovir / valganciclovir is co-administered with other medicines

known to be myelosuppressive or associated with renal impairment. This includes nucleoside

analogues

(e.g.

zidovudine,

didanosine,

stavudine),

immunosuppressants

(e.g.

ciclosporin,

tacrolimus, mycophenolate mofetil), antineoplastic agents (e.g. doxorubicin, vinblastine, vincristine,

hydroxyurea) and anti-infective agents (trimethoprim/sulphonamides, dapsone, amphotericin B,

flucytosine, pentamidine). Therefore, these medicines should be considered for concomitant use

with valganciclovir only if the potential benefits outweigh the potential risks (see section 4.4).

Zidovudine

Both zidovudine and ganciclovir have the potential to cause neutropenia and anaemia and a

pharmacodynamic interaction may occur during concomitant administration of these drugs. Some

patients may not tolerate concomitant therapy at full dosage (see section 4.4).

Didanosine

Didanosine plasma concentrations were found to be consistently raised when given with intravenous

ganciclovir. At intravenous doses of 5 and 10 mg/kg/day, an increase in the AUC of didanosine

ranging from 38 to 67% has been observed confirming a pharmacokinetic interaction during the

concomitant

administration

these

drugs.

There

significant

effect

ganciclovir

concentrations. Patients should be closely monitored for didanosine toxicity (e.g. pancreatitis) (see

section 4.4).

Probenecid

Probenecid given with oral ganciclovir resulted in statistically significantly decreased renal clearance

of ganciclovir (20%) leading to statistically significantly increased exposure (40%). These changes

were consistent with a mechanism of interaction involving competition for renal tubular excretion.

Therefore, patients taking probenecid and valganciclovir should be closely monitored for ganciclovir

toxicity.

4.6

Fertility, pregnancy and lactation

Fertility

In animal studies ganciclovir was found to impair fertility (see section 5.3). In a clinical study, renal

transplant patients receiving valganciclovir for CMV prophylaxis for up to 200 days were compared

to an untreated control group. Spermatogenesis was inhibited during treatment with valganciclovir.

At follow-up, approximately six months after treatment discontinuation, the mean sperm density in

treated patients was comparable to that observed in the untreated control group. In valganciclovir

treated patients, all patients with normal sperm density (n=7) and 8/13 patients with low sperm

density at baseline, had normal density after treatment cessation. In the control group, all patients

with normal sperm density (n=6) and 2/4 patients with low sperm density at baseline, had normal

density at the end of follow-up.

Page 5 of 20

Pregnancy

Pregnancy category D

The safety of valganciclovir for use in human pregnancy has not been established. However,

ganciclovir readily diffuses across the human placenta. The use of valganciclovir should be avoided

in pregnant women unless the benefit to the mother outweighs the potential risk to the foetus.

Reprotoxicity studies have not been repeated with valganciclovir because of the rapid and extensive

conversion to ganciclovir. In animal studies ganciclovir was associated with reproductive toxicity and

teratogenicity.

The safe use of valganciclovir during labour and delivery has not been established.

Breast-feeding

Peri- and post-natal development has not been studied with valganciclovir or with ganciclovir but the

possibility of ganciclovir being excreted in the breast milk and causing serious adverse reactions in

the nursing infant cannot be discounted. Human data are not available, but animal data indicates

that ganciclovir is excreted in the milk of lactating rats. Therefore, a decision should be made to

discontinue the medicine or discontinue nursing taking into consideration the potential benefit of

valganciclovir to the nursing mother.

Contraception in males and females

Women of reproductive potential should be advised to use effective contraception during and for at

least 30 days after treatment. Sexually active men are recommended to use condoms during and for

at least 90 days after cessation of treatment with valganciclovir (see section 5.1).

4.7

Effects on ability to drive and use machines

Adverse reactions such as seizures, dizziness, and confusion have been reported with the use of

valganciclovir and/or ganciclovir. If they occur, such effects may affect tasks requiring alertness

including the patient's ability to drive and operate machinery.

4.8

Undesirable effects

Clinical trials

Valganciclovir is a prodrug of ganciclovir, which is rapidly converted to ganciclovir after oral

administration. The undesirable effects known to be associated with ganciclovir usage can therefore

be expected to occur with valganciclovir. All of the adverse events observed in valganciclovir clinical

studies have been previously observed with ganciclovir. Therefore, adverse drug reactions reported

with intravenous or oral ganciclovir (no longer available) or with valganciclovir are included in the

table of adverse reactions (see Table 1).

In patients treated with valganciclovir/ganciclovir the most serious and frequent adverse drug

reactions are haematological reactions and include neutropenia, anaemia and thrombocytopenia.

The frequencies presented in the table of adverse reactions are derived from a pooled population of

patients (n=1704) receiving maintenance therapy with ganciclovir (GAN 1697, GAN 1653, 2304,

GAN 1774, GAN 2226, AVI 034, GAN 041) or valganciclovir (WV1537, WV15705). Exception is

made for anaphylactic reaction, agranulocytosis and granulocytopenia the frequencies of which are

derived from post-marketing experience.

Frequencies are presented as percentages and as CIOMS frequency categories defined as very

common (

1/10), common (

1/100 to < 1/10), uncommon (

1/1,000 to < 1/100), rare (

1/10,000

to < 1/1,000) and very rare (< 1/10,000).

The overall safety profile of ganciclovir/valganciclovir is consistent in HIV and transplant populations

except that retinal detachment has only been reported in patients with CMV retinitis. However, there

are some differences in the frequency of certain reactions. Valganciclovir is associated with a higher

Page 6 of 20

risk of diarrhoea compared to intravenous ganciclovir. Pyrexia, candida infections, depression,

severe neutropenia (ANC <500/µL) and skin reactions are reported more frequently in patients with

HIV. Renal and hepatic dysfunction are reported more frequently in organ transplant recipients.

Table 1.

Frequency of ganciclovir/valganciclovir ADRs reported in HIV patients

receiving maintenance therapy (n=1704)

ADR

(MedDRA)

System Organ Class

Percentage

Frequency

Category

Infections and infestations

Candid infections including oral candidiasis

22.42%

Very common

Upper respiratory tract infection

16.26%

Sepsis

6.92%

Common

Influenza

3.23%

Urinary tract infection

2.35%

Cellulitis

1.47%

Blood and lymphatic disorders

Neutropenia

26.12%

Very common

Anaemia

19.89%

Thrombocytopenia

7.34%

Common

Leucopenia

3.93%

Pancytopenia

1.06%

Bone marrow failure

0.29%

Uncommon

Aplastic anaemia

0.06%

Rare

Agranulocytosis*

0.02%

Granulocytopenia*

0.02%

Immune system disorders

Hypersensitivity

1.12%

Common

Anaphylactic reaction*

0.02%

Rare

Metabolic and nutrition disorders

Decreased appetite

12.09%

Very common

Weight decreased

6.46%

Common

Psychiatric disorders

Depression

6.69%

Common

Confusional state

2.99%

Anxiety

2.64%

Agitation

0.59%

Uncommon

Psychotic disorder

0.23%

Thinking abnormal

0.18%

Hallucinations

0.18%

Nervous system disorders

Headache

17.37%

Very common

Insomnia

7.22%

Common

Neuropathy peripheral

6.16%

Page 7 of 20

ADR

(MedDRA)

System Organ Class

Percentage

Frequency

Category

Dizziness

5.52%

Paraesthesia

3.58%

Hypoaesthesia

2.58%

Convulsion

2.29%

Dysgeusia (taste disturbance)

1.35%

Tremor

0.88%

Uncommon

Eye disorders

Visual impairment

7.10%

Common

Retinal detachment**

5.93%

Vitreous floaters

3.99%

Eye pain

2.99%

Conjunctivitis

1.58%

Macular oedema

1.06%

Ear and labyrinth disorders

Ear pain

1.17%

Common

Deafness

0.65%

Uncommon

Cardiac disorders

Cardiac arrhythmias

0.47%

Uncommon

Vascular disorders

Hypotension

2.05%

Common

Respiratory, thoracic and mediastinal disorders

Cough

18.31%

Very common

Dyspnoea

11.80%

Gastrointestinal disorders

Diarrhoea

34.27%

Very common

Nausea

26.35%

Vomiting

14.85%

Abdominal pain

10.97%

Dyspepsia

4.81%

Common

Flatulence

4.58%

Abdominal pain upper

4.58%

Constipation

3.70%

Mouth ulceration

3.17%

Dysphagia

2.93%

Abdominal distention

2.41%

Pancreatitis

1.64%

Hepatobiliary disorders

Blood alkaline phosphatase increased

3.58%

Common

Hepatic function normal

3.23%

Aspartate aminotransferase increased

1.88%

Page 8 of 20

ADR

(MedDRA)

System Organ Class

Percentage

Frequency

Category

Alanine aminotransferase increased

1.23%

Skin and subcutaneous tissues disorders

Dermatitis

11.80%

Very common

Night sweats

7.92%

Common

Pruritis

4.58%

Rash

2.52%

Alopecia

1.29%

Dry skin

0.94%

Uncommon

Urticaria

0.70%

Musculoskeletal and connective tissue disorders

Back pain

4.46%

Common

Myalgia

3.52%

Arthralgia

3.35%

Muscle spasms

2.99%

Renal and urinary disorders

Renal impairment

2.52%

Common

Creatinine clearance renal decreased

2.35%

Blood creatinine increased

1.88%

Renal failure

0.76%

Uncommon

Haematuria

0.70%

Reproductive system and breast disorders

Infertility male

0.23%

Uncommon

General disorders and administration site conditions

Pyrexia

33.51%

Very common

Fatigue

18.96%

Pain

5.81%

Common

Chills

5.40%

Malaise

2.11%

Asthenia

2.00%

Chest pain

0.88%

Uncommon

* The frequencies of these adverse reactions are derived from post-marketing experience.

** Retinal detachment has only been reported in AIDS patients treated for CMV retinitis

Description of selected adverse reactions

Neutropenia

The risk of neutropenia is not predictable on the basis of the number of neutrophils before treatment.

Neutropenia usually occurs during the first or second week of induction therapy. The cell count

usually normalizes within 2 to 5 days after discontinuation of the drug or dose reduction (see section

4.4).

Page 9 of 20

Thrombocytopenia

Patients with low baseline platelet counts (< 100,000 /mL) have an increased risk of developing

thrombocytopenia.

Patients

with

iatrogenic

immunosuppression

treatment

with

immunosuppressive drugs are at greater risk of thrombocytopenia than patients with AIDS (see

section 4.4). Severe thrombocytopenia may be associated with potentially life-threatening bleeding.

Influence of treatment duration or indication on adverse reactions

Severe neutropenia (ANC <500/µL) is seen more frequently in CMV retinitis patients (16%)

undergoing

treatment

with

valganciclovir

than

solid

organ

transplant

patients

receiving

valganciclovir or oral ganciclovir. In patients receiving valganciclovir or oral ganciclovir until Day 100

post-transplant, the incidence of severe neutropenia was 5% and 3% respectively, whilst in patients

receiving valganciclovir until Day 200 post-transplant the incidence of severe neutropenia was 10%.

There was a greater increase in serum creatinine seen in solid organ transplant patients treated until

Day 100 or Day 200 post-transplant with both valganciclovir and oral ganciclovir when compared to

CMV retinitis patients. However, impaired renal function is a feature more frequent in solid organ

transplantation patients.

The overall safety profile of valganciclovir did not change with the extension of prophylaxis up to

200 days in high risk kidney transplant patients. Leukopenia was reported with a slightly higher

incidence in the 200 days arm while the incidence of neutropenia, anaemia and thrombocytopenia

were similar in both arms.

Paediatric patients

Valganciclovir has been studied in 179 paediatric solid organ transplant patients who were at risk of

developing CMV disease (aged 3 weeks to 16 years) and in 133 neonates with symptomatic

congenital CMV disease (aged 2 to 31 days), with duration of ganciclovir exposure ranging from 2 to

200 days (see section 4.8).

The overall safety profile was similar in paediatric patients as compared to adults. Neutropenia was

also reported with slightly higher incidence in the two paediatric studies as compared to adults, but

neutropenia

infectious

adverse

events

were

generally

correlated

paediatric

populations.

In kidney transplant paediatric patients, prolongation of valganciclovir exposure to 200 days was not

associated with increased incidence of adverse events.

Congenital CMV

Congenital CMV is not an approved indication for valganciclovir in New Zealand. However, studies

conducted in neonates and infants with congenital CMV do provide safety data in this patient

population. Studies suggest that the safety of valganciclovir tablets and ganciclovir injection appear

consistent with the known safety profile of valganciclovir/ganciclovir. The primary toxicity is

neutropenia, in one study 9 of 24 subjects (38%) developed Grade 3 or 4 neutropenia while on

ganciclovir therapy (one patient required treatment cessation). Most events were manageable with

continuation of antiviral therapy. Growth (head circumference, weight and height) of all neonates,

who had growth measurements recorded, increased over time in this non-comparative study. The

most frequent treatment-related AEs associated with oral valganciclovir were neutropenia, anaemia,

liver function abnormality and diarrhoea, all seen more frequently in the placebo group. The only

treatment-related SAEs were neutropenia and anaemia, both seen more frequently in the placebo

arm. No statistically or clinically significant differences were observed in the rate of growth (average

head circumference, weight and length) over time at each time point between the two treatment

groups.

Laboratory abnormalities

Laboratory abnormalities reported in adult CMV retinitis and solid organ transplant (SOT) patients

receiving valganciclovir until Day 100 post-transplant are listed in Table 2. The evidence of laboratory

Page 10 of 20

abnormalities was comparable with the extension of prophylaxis up to 200 days in high risk kidney

transplant patients.

Laboratory abnormalities reported in paediatric SOT patients are listed in Table 3. The incidence of

severe neutropenia (ANC<500/µL) was higher in paediatric kidney patients treated until Day 200 as

compared to paediatric patients treated until Day 100 and as compared to adult kidney transplant

patients treated until Day 100 or Day 200.

Table 2.

Laboratory abnormalities in adult patients

Laboratory Abnormalities

CMV Retinitis

Patients

Solid Organ Transplant Patients

Valganciclovir

(n = 370)

Valganciclovir

(n = 244)

Oral ganciclovir

(n = 126)

%

%

%

Neutropenia (ANC/ microlitre)

< 500

500 - < 750

750 - < 1000

Anaemia (haemoglobin g/dL)

< 6.5

6.5 - < 8.0

8.0 - < 9.5

Thrombocytopenia (platelets/microlitre)

< 25000

25000 - < 50000

50000 - < 100000

Serum creatinine (mg/dL)

> 2.5

> 1.5 – 2.5

Table 3.

Laboratory abnormalities in paediatric solid organ transplant patients

Laboratory Abnormalities

Valganciclovir in Paediatric SOT Patients

Dosing until Day 100

Dosing until Day 200

Post-Transplant n = 63

Post-Transplant n = 56

%

%

Neutropenia (ANC/ microlitre)

< 500

500 - < 750

750 - < 1000

Anaemia (haemoglobin g/dL)

< 6.5

6.5 - < 8.0

8.0 - < 9.5

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