PROFESSIONAL INFORMATION FOR VALHET ORAL SOLUTION

SCHEDULING STATUS

signiﬁcantly increase exposure (40 %). These changes were consistent with a mechanism of interaction involving

competition for renal tubular excretion. Therefore, patients taking probenecid and VALHET ORAL SOLUTION should

be closely monitored for ganciclovir toxicity.

The majority of patients experienced one or more of the following adverse events:

PATIENT INFORMATION LEAFLET FOR VALHET ORAL SOLUTION

Not all side eﬀects reported for VALHET ORAL SOLUTION are included in this leaﬂet. Should your general health

worsen or if you experience any untoward eﬀects while taking VALHET ORAL SOLUTION, please consult your health

care provider for advice.

Haematological toxicity: pancytopenia, bone marrow depression, medullary aplasia, leukopenia, neutropenia,

granulocytopenia.

SCHEDULING STATUS

Hepatotoxicity: hepatitis, liver function disorder.

Renal toxicity: worsening of haematuria in a patient with pre-existing renal impairment, acute renal failure,

elevated creatinine.

Gastrointestinal toxicity: abdominal pain, diarrhoea, vomiting.

Neurotoxicity: generalised tremor, convulsion.

Zidovudine

If any of the following happens, stop taking VALHET ORAL SOLUTION and tell your doctor immediately or go to the

casualty department at your nearest hospital:

When zidovudine was given in the presence of oral ganciclovir there was a small (17 %), but statistically signiﬁcant

increase in the AUC of zidovudine. There was also trend towards lower ganciclovir concentrations when administered

with zidovudine, although this was not statistically signiﬁcant. However, since both zidovudine and ganciclovir have the

potential to cause neutropenia and anaemia, some patients may not tolerate concomitant therapy at full dosage (see

section 4.4).

1 NAME OF THE MEDICINE

VALHET ORALSOLUTION50 mg/ mL(powder for oral solution)

VALHET ORAL SOLUTION 50 mg/ mL (powder for oral solution)

Valganciclovir hydrochloride

Preservative: Sodium benzoate 1 mg/mL

Contains sugar (57,150 mg mannitol per mL)

Contains sweetener (0,300 mg saccharin sodium per mL)

•

swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause diﬃculty in swallowing or

breathing,

2 QUALITATIVEAND QUANTITATIVE COMPOSITION

Each mL of constituted oral solution contains valganciclovir free base 50 mg equivalent to 55,15 mg of valganciclovir

hydrochloride.

•

rash or itching,

fainting

5 PHARMACEUTICALPROPERTIES

Didanosine

These are all very serious side eﬀects. If you have them, you may have had a serious reaction to VALHET ORAL

SOLUTION.You may need urgent medical attention or hospitalisation.

5.1 Pharmacodynamic properties

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

and oral).At ganciclovir oral doses of 3 and 6 g/day, an increase in theAUC of didanosine ranging from 84 to 124 % has

been observed. This increase cannot be explained by competition for renal tubular secretion, as there was an increase

in the percentage of didanosine dose excreted. This increase could arise from either increased bioavailability or

decreased metabolism. There was no clinically signiﬁcant eﬀect on ganciclovir concentrations. However, given the

increase in didanosine plasma concentrations in the presence of ganciclovir, patients should be closely monitored for

didanosine toxicity (see section 4.4).

Preservative: Sodium benzoate 1 mg/mL.

Contains sugar (57,150 mg mannitol per mL).

Contains sweetener (0,300 mg saccharin sodium per mL).

Pharmacological classiﬁcation:A20.2.8Antiviral agents

Pharmacotherapeutic group: antivirals for systemic use, nucleosides and nucleotides excl. reverse transcriptase

inhibitors. ATC code:J05AB14

Read all of this leaﬂet carefully before you start taking VALHET ORALSOLUTION

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

•

Keep this leaﬂet.You may need to read it again.

If you have further questions, please ask your doctor, pharmacist, nurse or other health care provider.

VALHET ORALSOLUTIONhas been prescribed for you personally and you should not share your medicine with

other people. It may harm them, even if their symptoms are the same as yours.

fever, fatigue, sore throat, swollen lymph glands – these may be signs of infection due to a reduction in the

number of your white blood cells bruising and bleeding, which may indicate a change in your blood cells

feeling short of breath or having trouble breathing (dyspnoea)

blurred vision, inability to see in dim light, partial loss of vision, seeing ﬂashes of light, seeing spots, sensitivity to

light, vision loss these may indicate a detached retina

inﬂammation of cellular tissue (cellulitis), inﬂammation or infection of the kidneys or bladder

a rise in some liver enzymes, which will only be seen during blood tests

changes to the normal working of the kidneys

depression

deafness

For a full list of excipients, see section 6.1.

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir. After oral administration, valganciclovir is rapidly and

extensively metabolised to ganciclovir by intestinal and hepatic esterases.

Ganciclovir is a synthetic analogue of 2'-deoxyguanosine and inhibits replication of herpes viruses in vitro and in vivo. In

vitro sensitive human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and -2 (HSV-1 and

HSV-2), human herpes virus -6, -7 and -8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster virus

(VZV) and hepatitis B virus (HBV).

•

3 PHARMACEUTICALFORM

VALHET ORAL SOLUTION is white to slightly yellow coloured powder. The constituted solution is a colourless to

brownish yellowTutti-Frutti ﬂavoured clear solution.

Mycophenolate Mofetil

What is in this leaﬂet

Based on the results of a single dose administration study of recommended doses of oral mycophenolate mofetil (MMF)

and intravenous ganciclovir and the known eﬀects of renal impairment on the pharmacokinetics of MMF and

ganciclovir, it is anticipated that co-administration of these medicines (which have the potential to compete for renal

tubular secretion) will result in increase in phenolic glucuronide of mycophenolic acid (MPAG) and ganciclovir

concentration. No substantial alteration of mycophenolic acid (MPA) pharmacokinetics is anticipated and MMF dose

adjustment is not required. ln patients with renal impairment in which MMF and ganciclovir are co-administered, the

dose recommendation of ganciclovir should be observed, and patients monitored carefully.

1. WhatVALHET ORALSOLUTIONis and what it is used for

2. What you need to know before you takeVALHET ORALSOLUTION

3. How to takeVALHET ORALSOLUTION

4. Possible side eﬀects

5. How to storeVALHET ORALSOLUTION

6. Contents of the pack and other information

•

4 CLINICALPARTICULARS

4.1 Therapeutic indications

VALHET ORALSOLUTIONis indicated for:

Ganciclovir requires phosphorylation to its triphosphate form for antiviral activity.

The treatment of cytomegalovirus (CMV) retinitis in acquired immunodeﬁciency syndrome (AIDS) patients.

The prevention of CMV disease in solid organ transplant patients who are at risk i.e., donor seropositive and

recipient seronegative.

In CMV-infected cells, ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase,

pUL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly

metabolised intercellularly. Triphosphate metabolism has been shown to occur in HSV- and HSMV-infected cells with

half-lives of 18 and between 6 and 24 hours respectively, after the removal of extracellular ganciclovir.

inﬂammation of the pancreas (pancreatitis) where you may notice severe pain in the stomach and back

blood in the urine, kidney failure

Zalcitabine

Zalcitabine increased theAUC_0-8hof oral ganciclovir by 13 %. There were no statistically signiﬁcant changes in any of the

other pharmacokinetic parameters assessed. Additionally, there were no clinically relevant changes in zalcitabine

pharmacokinetics in the presence of oral ganciclovir although a small increase in the elimination rate constant was

observed.

Both VALHET ORAL SOLUTION and zalcitabine have the potential to cause peripheral neuropathy and patients

should be monitored for such events.

1. What VALHET ORALSOLUTION is and what it is used for

VALHET ORALSOLUTIONbelongs to a group of medicines that work to prevent the growth of viruses.

VALHET ORALSOLUTIONis used:

4.2 Posology and method of administration

Posology

Strict adherence to dosage recommendations is essential to avoid overdose.

The bioavailability of ganciclovir from VALHET ORAL SOLUTION is up to 10-fold higher than from ganciclovir

capsules, therefore the dosage and administration of VALHET ORALSOLUTIONshould be closely followed.

These are all serious side eﬀects.You may need urgent medical attention.

As phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in

virus-infected cells.

Tell your doctor as soon as possible if you notice any of the following:

Frequent:

The virus static activity of ganciclovir is due to inhibition of viral DNAsynthesis by:

a) ganciclovir triphosphate competitively inhibiting the incorporation of deoxyguanosine-triphosphate (dGTP) into

DNAby viral DNApolymerase, and

•

for the treatment of cytomegalovirus (CMV)-infections of the retina of the eye in adult patients with acquired

immunodeﬁciency syndrome (AIDS). CMV-infection of the retina of the eye can cause vision problems and even

blindness.

to prevent CMV-infections in adults and children who are not infected with CMV and who have received an organ

transplant from somebody who was infected by CMV.

•

fungal infection in the mouth (oral candidiasis), infections caused by bacteria or viruses in the blood

swollen stomach, mouth ulcers

diarrhoea

a reduction in the pigment in the blood that carries oxygen (anaemia) - which can cause tiredness and

breathlessness

headache

red, swollen eyes (conjunctivitis), abnormal vision

diﬃculty sleeping

strange tastes

decreased sense of touch

prickly or tingling skin

loss of feeling in the hands or feet

dizziness

b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited, further viral DNA

The ganciclovir systemic exposure following administration of 900 mg valganciclovir oral solution is equivalent to a

dose of 900 mg valganciclovir tablets(2 x450 mg tablets).

Stavudine

No statistically signiﬁcant pharmacokinetic interactions were observed when stavudine and oral ganciclovir were given

in combination.

elongation.

•

Viral resistance:

Standard dosage in adults

Inductiontreatment of CMV retinitis

For patients with active CMV retinitis, the recommended dose is 900 mg VALHET ORAL SOLUTION twice a day for 21

days. Prolonged induction treatment may increase the risk of bone marrow toxicity.

Viral resistance to ganciclovir can arise after chronic dosing with valganciclovir by selection of mutations in either the

viral kinase gene (UL97) responsible for ganciclovir monophosphorylation and/or the viral polymerase gene (UL54).

Viruses containing mutations in the UL97 gene are resistant to ganciclovir alone, whereas virus with mutations in the

UL54 gene are resistant to ganciclovir but may show cross-resistance to other antivirals that also target the viral

polymerase.

Trimethoprim

After taking VALHET ORAL SOLUTION, the valganciclovir is quickly changed in your body to release ganciclovir,

which is the active medicine. Ganciclovir prevents the growth and the increase in numbers of

cytomegalovirus (CMV).

•

Trimethoprim statistically signiﬁcantly decreased the renal clearance of oral ganciclovir by 16,3 % and this was

associated with a statistically signiﬁcant decrease in the terminal elimination rate and the corresponding increase in

half-life by 15 %. However, these changes are unlikely to be clinically signiﬁcant, as AUC_0-8hand C_maxwere unaﬀected.

The only statistically signiﬁcant change in trimethoprim pharmacokinetic parameters when co-administered with

ganciclovir was a 12 % increase in C_min. However, this is unlikely to be of clinical signiﬁcance and no dose adjustment is

recommended.

virus called

Maintenance treatment of CMV retinitis

2. What you need to know before you take VALHET ORALSOLUTION

Do not take VALHET ORALSOLUTION:

Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is 900 mg VALHET

ORAL SOLUTION once daily. Patients whose retinitis worsens may repeat induction treatment; however,

consideration should be given to the possibility of viral medicine resistance.

Antiviral activity:

The in vitro anti-viral activity, measured as IC₅₀of ganciclovir against CMV, is in the range of 0,08 µM (0,02 µg/mL) to 14

µM (3,5 µg/mL).

•

If you are hypersensitive (allergic) to valganciclovir, ganciclovir, aciclovir, valaciclovir or any of the other

ingredients of VALHET ORALSOLUTION (listed in section 6).

If you are breastfeeding.

If you have ever had an allergic reaction to acyclovir or valaciclovir (used to treat viral infections caused by

herpes simplex including cold sores).

Ciclosporin

There was no evidence that introduction of ganciclovir aﬀects the pharmacokinetics of ciclosporin based on the

comparison of ciclosporin trough concentrations. However, there was some evidence of increases in the maximum

serum creatinine value observed following initiation of ganciclovir therapy.

Prevention of CMV disease in solid organ transplantation

For kidney transplant patients, the recommended dose is 900 mg once daily depending on creatinine clearance,

starting within 10 days of transplantation until 200 days post-transplantation.

For patients who have received a solid organ transplant other than the kidney, the recommended dose is 900 mg daily,

starting within 10 days of transplantation until 100 days post transplantation.

•

5.2 Pharmacokinetic properties

Absorption

Valganciclovir is a prodrug of ganciclovir. It is well absorbed from the gastrointestinal tract and rapidly and extensively

metabolised in the intestinal wall and liver to ganciclovir. The absolute bioavailability of ganciclovir from valganciclovir is

approximately 60 %. Systemic exposure to valganciclovir is transient and low. Valganciclovir allows systemic exposure

of ganciclovir similar to that achieved with recommended doses ofIV ganciclovir.

ﬁts (convulsions)

eye pain, swelling within the eye

earache

coughing

feeling sick (nausea) and being sick (vomiting), stomach ache, constipation, wind, indigestion, diﬃculty

swallowing

Other potential medicine interactions

Toxicity may be enhanced when ganciclovir is co-administered with, or is given immediately before or after, other

medicines that inhibit replication of rapidly dividing cell populations such as those occurring in the bone marrow, tested

and germinal layers of the skin and gastrointestinal mucosa, or that are associated with renal impairment (such as

dapsone, pentamidine, ﬂucytosine, vincristine, vinblastine, adriamycin, amphotericin B, sulfamethoxazole-

trimethoprim combinations, nucleoside analogues and hydroxyurea) therefore these medicines should be considered

for concomitant use with VALHET ORAL SOLUTION only if the potential beneﬁts outweigh the potential risks (see

section 4.4).

Warnings and precautions

Take special care with VALHET ORALSOLUTION:

Special populations

Patients with renal impairment

Serum creatinine levels or creatinine clearance should he monitored carefully. Dosage adjustment is required for adult

patients based on creatinine clearance, as shown intable 1below.

Creatinine clearance (mL/min) is calculated from serum creatinine by the following formulae:

AUC₂₄and C_maxfor valganciclovir are approximately 1 % and 3 % of those of ganciclovir, respectively. For comparison,

the bioavailability of ganciclovir after administration of 1 000 mg oral ganciclovir (as capsules) is 6 – 8 %.

•

If you have low numbers of white blood cells, red blood cells or platelets (small cells involved in blood

clotting) in your blood.

Your doctor will carry out blood tests before you start taking VALHET ORAL SOLUTION and more tests will

be done while you are taking the powder for oral solution.

If you are having radiotherapy or haemodialysis. If your doctor decides to give you VALHET ORAL

SOLUTION, your blood will need to be checked frequently.

If you have a problem with your kidneys. Your doctor may need to prescribe a reduced dose for you and may need

to check your blood frequently during treatment.

If you are currently taking ganciclovir capsules and your doctor wants you to switch to VALHET ORAL

SOLUTION powder for oral solution. It is important that you do not take more than the prescribed dose by

your doctor or you could risk an overdose.

VALHET ORAL SOLUTION can cause potential birth defects. If you are a woman, and able to get pregnant you

should use eﬀective contraception during your treatment and for 30 days after treatment has ended. Men must

be advised to use a condom during treatment, and for 90 days after treatment.

VALHET ORAL SOLUTION powder for oral solution and reconstituted solution should be handled with caution.

If the powder or solution makes direct contact with skin, the area should be washed thoroughly with soap and

water. If the solution gets into the eye, the eye should immediately be thoroughly washed with water.

•

inﬂamed skin, itching, sweating at night, hair loss (alopecia)

back pain, pain in the muscles or joints, stiﬀ muscles, muscle cramps

loss of appetite (anorexia), weight loss

tiredness, fever, pain, loss of energy, generally feeling unwell

feeling anxious, confused, having unusual thoughts

chest pain

Valganciclovir in HIV+, CMV+ patients:

Systemic exposure of HIV+, CMV+ patients after twice daily administration of ganciclovir and valganciclovir for one

(140 – age) × (Wt [kg]) x constant*

CrCl(mL/min)=

Other antiretrovirals

Cytochrome P450 isoenzymes play no role in ganciclovir pharmacokinetics. As a consequence, pharmacokinetic

interactions with protease inhibitors and non-nucleoside reverse transcriptase inhibitors are not anticipated.

•

r[µmol/L]

week is:

Table 2:

Parameter

* Constant =1,23 for males and 1,04 for females (0,85 x 1,23 = 1,04)

The South African Nephrology Society recommends simplifying the above formula by omitting the constant of 1,23 for

males.

Ganciclovir (5 mg/kg, i,v)

n =18

Valganciclovir (900 mg, once daily)

n = 25

4.6 Fertility, pregnancy and lactation

Contraception in males and females

As a result of the potential for reproductive toxicity and teratogenicity, women of childbearing potential must be advised

to use eﬀective contraception during and for at least 30 days after treatment. Male patients must be advised to practice

barrier contraception during and for at least 90 days following treatment with valganciclovir unless it is certain that the

female partner is not at risk of pregnancy.

low blood pressure, which can cause you to feel light-headed or faint

Ganciclovir

32,8 ± 10.1

6,7 ± 2,1

Valganciclovir

0,37 ± 0,22

0,18 ± 0,06

(140 – age) × (Wt [kg]) x 0,85 (if female)

CrCl(mL/min)=

AUC (0 – 12 h) (µg.h/mL)

C_max(µg/mL)

28,0 ± 9,0

10,4 ± 4,9

r[µmol/L]

Less frequent:

•

CrCl= creatinine clearance

SCr= serum creatinine

•

changes to your normal heartbeat

shaking or trembling

itchy rash or swellings (urticaria), dry skin

a rise in the liver enzyme called alanine aminotransferase (which will only be seen during blood tests)

having unusual changes in mood and behaviour, losing contact with reality such as hearing voices or seeing

things that are not there, feeling agitated

infertility in men

The eﬃcacy of ganciclovir in increasing the time to progression of CMV retinitis has been shown to correlate with

systemic exposure (AUC).

Pregnancy

Table 1: VALHET ORAL SOLUTION dose for renally impaired patients

CrCl (mL/min)

VALHET ORALSOLUTIONshould not be used in pregnancy.

Valganciclovir in solid organ transplant patients:

Steady state systemic exposure of solid organ transplant patients to ganciclovir after daily oral administration of

ganciclovir and valganciclovir is:

Induction dose of

VALHET ORAL SOLUTION

Maintenance/prevention dose of

VALHET ORAL SOLUTION

900 mg once daily

450 mg once daily

225 mg once daily

The safety of VALHET ORAL SOLUTION for use in pregnant women has not been established. Its active metabolite,

ganciclovir, readily diﬀuses across the human placenta. Based on its pharmacological mechanism of action and

reproductive toxicity observed in animal studies with ganciclovir there is a theoretical risk of teratogenicity in humans.

≥ 60

900 mg twice daily

450 mg twice daily

Children and adolescents

Safety and eﬃcacy ofVALHET ORALSOLUTIONuse in children has not been established.

Table 3:

Parameter

40 – 59

25 – 39

10 – 24

< 10

•

Breastfeeding

Ganciclovir (1000 mg three daily) Valganciclovir (900 mg, once Daily)

n =82 n =161 Ganciclovir

450 mg once daily

225 mg once daily

200 mg (3 x weekly after dialysis)

It is unknown if ganciclovir is excreted in human breast milk, but the possibility of ganciclovir being excreted in the

breastmilk and causing serious adverse reactions in the nursing infant cannot be discounted. Animal data indicate that

ganciclovir is excreted in the milk of lactating rat. Therefore, breast-feeding must be discontinued during treatment with

valganciclovir (see section 4.3).

If you notice any side eﬀects not mentioned in this leaﬂet, please inform your doctor or pharmacist.

Other medicines andVALHET ORALSOLUTION

125 mg once daily

100 mg (3 x weekly after dialysis)

AUC (0 – 24 h) (µg.h/mL)

C_max(µg/mL)

The systemic exposure of ganciclovir to heart, kidney and liver transplant recipients was similar after oral administration

28,0 ± 10,9

1,4 ± 0,5

46,3 ± 15,2

5,3 ± 1,5

Always tell your health care provider if you are taking any other medicine. (this included all complementary or traditional

medicines). The use of VALHET ORAL SOLUTION with these medicines may cause undesirable interactions. Please

consult your doctor, pharmacist or other healthcare professional for advice.

Reporting of side eﬀects

If you get side eﬀects, talk to your doctor, pharmacist or nurse. You can also report side eﬀects to SAHPRAvia the Med

Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website or to the

Holder of certiﬁcate of registration through the mail: pvg.cdma@heterogroups.com. By reporting side eﬀects, you can

help provide more information on the safety of VALHET ORALSOLUTION.

Patients undergoinghaemodialysis

Dosage adjustment is necessary for patients on haemodialysis (CrCl < 10 mL/min) and a dosing recommendation for

VALHET ORALSOLUTIONpowder for oral solution is given in the above table.

Patients with severe leukopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia

Severe leukopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia, bone marrow depression and

aplastic anaemia have been observed in patients treated with VALHET ORAL SOLUTION (and ganciclovir). Therapy

should not be initiated if the absolute neutrophil count is less than 500 cells/µL or the platelet count is less than 25

000/µLor the haemoglobin is less than 8 g/dL(see section 4.4)

Elderly

Safety and eﬃcacy have not been established.

Paediatric population

Safety and eﬃcacy have not been established in adequate and well-controlled clinical studies.

Fertility

of valganciclovir according to the renal function dosing algorithm.

A clinical study with renal transplant patients receiving valganciclovir for CMV prophylaxis for up to 200 days

demonstrated an impact of valganciclovir on spermatogenesis, with decreased sperm density and motility measured

after treatment completion. This eﬀect appears to be reversible and approximately six months after valganciclovir

discontinuation, mean sperm density and motility recovered to levels comparable to those observed in the untreated

controls.

Tell your doctor if you are already taking medicines that contain any of the following:

Following the administration of valganciclovir as an oral solution, equivalent systemic ganciclovir exposures were

obtained compared to the tablet formulation.

•

Imipenem-cilastatin (an antibiotic).Taking this withVALHET ORALSOLUTIONcan cause convulsions (ﬁts).

Zidovudine, didanosine, lamivudine, tenofovir, abacavir, emtricitabine or similar kinds of medicines used to treat

5. How to store VALHET ORALSOLUTION

Food: When valganciclovir was given with food at the recommended dose of 900 mg, increases were seen in both

mean ganciclovir AUC₂₄(± 30 %) and mean ganciclovir C_maxvalues (± 14 %), it is recommended that valganciclovir be

administered with food.

AIDS.Your doctor may reduce the dose of didanosine that you need to take.

Probenecid (a medicine against gout). Taking probenecid and VALHET ORAL SOLUTION at the same time

•

Store at or below 25 °C.

•

Reconstituted solution to be stored not longer than 49 days at 2 °C to 8 °C.

Protect from light and moisture.

Bottle must be kept tightly-closed.

Keep the bottle in the outer carton until required for use.

Store all medicines out of reach of children.

Do not store in a bathroom.

Do not use after the expiry date stated on the label / carton / bottle.

Return all unused medicine to your pharmacist.

Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).

In animal studies, ganciclovir impaired fertility in male and female mice and has shown to inhibit spermatogenesis and

induce testicular atrophy in mice, rats and dogs at doses considered clinically relevant.

could increase the amount of ganciclovir in your blood.

Mycophenolate mofetil (used after organ transplantations).

Distribution

Plasma protein binding of ganciclovir was 1 – 2 % over concentrations of 0,5 and 51 µg/mL. The steady state volume of

distribution of ganciclovir afterIVadministration was 0,680 ± 0,161 L/kg.

•

Based on clinical and nonclinical studies, it is considered likely that ganciclovir (and valganciclovir) may cause

temporary or permanent inhibition of human spermatogenesis (see section 4.4).

Vincristine, vinblastine, adriamycin, hydoxyurea or similar kinds of medicines to treat cancer.

Trimethoprim, trimethoprim/sulpha combinations and dapsone (antibiotics).

Pentamidine (medicine to treat parasite or lung infections).

Biotransformation

4.7 Eﬀects on ability to drive and use machines

Valganciclovir is rapidly and extensively metabolised to ganciclovir, no other metabolites have been detected. No

metabolite of orally administered radiolabelled ganciclovir (1 000 mg single dose) accounted for more than 1 – 2 % of

the radioactivity recovered in the faeces and urine.

Convulsions, sedation, dizziness, ataxia and/or 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.

Flucytosine or amphotericin B (antifungal medicines).

Method of administration

VALHET ORALSOLUTIONis administered orally and should be taken with food.

VALHET ORALSOLUTION, preparation of solution:

Elimination

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your

doctor, pharmacist or other health care provider for advice before takingVALHET ORALSOLUTION.

The major route of elimination of valganciclovir as ganciclovir is renal excretion, by glomerular ﬁltration and active

tubular secretion. Renal clearance accounts for 81,5 % ± 22 % of the systemic clearance of valganciclovir. The half-life

of ganciclovir from valganciclovir is 4,1 ± 0,9 hours in HIV- and CMV-seropositive patients.

4.8 Undesirable eﬀects

a) Summary of the safety proﬁle

1. Measure 91 mLof puriﬁed water in a graduated cylinder.

2. Add puriﬁed water to the bottle. Shake the closed bottle until the powder is dissolved.

3. Remove the child resistant cap and push the bottle adapter into the neck of the bottle.

4. Close bottle tightly with child resistant cap.

Forfurther instructions on handling VALHET ORALSOLUTIONsee section 6.6.

4.3 Contraindications

6. Contents of the pack and other information

What VALHET ORALSOLUTION contains

The active substance is valganciclovir hydrochloride.

The other ingredients are anhydrous citric acid, mannitol, povidone, sodium benzoate, saccharin sodium,

puriﬁed water, Tutti Frutti ﬂavour 051880 AP0551 contains maize maltodextrin, ﬂavourings, INS 1520

polypropylene glycol, INS 307 c dl-alpha-tocopherol

Valganciclovir is a prodrug of ganciclovir. It is rapidly converted to ganciclovir after oral administration. The side eﬀects

known to be associated with ganciclovir usage can therefore be expected to occur with valganciclovir administration.

All of the undesirable eﬀects observed in valganciclovir have been previously observed with ganciclovir. The most

frequently reported adverse medicine reactions following administration of valganciclovir in adults are neutropenia,

anaemia and diarrhoea.

Valganciclovir is associated with a higher risk of diarrhoea compared to intravenous ganciclovir.

Severe neutropenia (< 500ANC/µL) has been seen more frequently in CMV retinitis patients undergoing treatment with

valganciclovir than in solid organ transport patients receiving valganciclovir.

Pharmacokinetics in special populations

Patients with renal impairment:

Pregnancy

VALHET ORALSOLUTION should not be given to pregnant women because it is possible that this could lead to

the loss of the baby or to the birth of a malformed baby or to problems in the baby after birth.

•

Decreasing renal function resulted in decreased clearance of ganciclovir from valganciclovir with an increase in

terminal half-life.Therefore, dosage adjustment is required for renally impaired patients (see section 4.2).

Haemodialysis:

•

–

Breastfeeding

You must not take VALHET ORALSOLUTION if you are breastfeeding. If your doctor wants you to begin treatment with

VALHET ORALSOLUTIONyou must stop breastfeeding before you start to take your oral solution.

VALHET ORAL SOLUTION is contraindicated in patients with hypersensitivity to valganciclovir, ganciclovir or

any of the excipients listed in section 6.1.

Due to the similarity of the chemical structure of VALHET ORAL SOLUTION and that of aciclovir and

valaciclovir, a cross-hypersensitivity reaction between these medicines is possible.

VALHET ORAL SOLUTION is contraindicated during breast-feeding (see section 4.6).

For patients receiving haemodialysis (CrCl < 10 mL/min) valganciclovir oral solution is recommended to provide an

individualised dose (see section 4.2).

WhatVALHET ORALSOLUTION looks like and contents of the pack

VALHET ORAL SOLUTION is white to slightly yellow coloured powder. The constituted solution is a colourless to

brownish yellow tutti-frutti ﬂavoured clear solution.

Patients with hepatic impairment:

b) Tabulated summary of adverse reactions

System organ class

The pharmacokinetics of valganciclovir in suitable liver transplant recipients were investigated in one open-label 4-

crossover study. The absolute bioavailability of ganciclovir from valganciclovir following a single dose of 900 mg

valganciclovir under fed conditions was approximately 60 %, in agreement with estimates obtained in other patient

populations. Ganciclovir AUC_0-24was comparable to that achieved by 5 mg/kg IV ganciclovir in liver transplant

recipients.

Fertility

Frequency

Frequent

Adverse event

Oral candidiasis, sepsis (bacteraemia, viraemia), cellulitis,

urinary tract infection, upper respiratory tract infection,

It is also extremely important that both men and women of childbearing age use eﬀective contraception when

taking VALHET ORAL SOLUTION. if you need advice on contraception, ask your doctor before you start to take

VALHET ORAL SOLUTION. Men whose partners could become pregnant should use condoms while taking VALHET

ORAL SOLUTION and should continue to use condoms for 90 days after treatment has ﬁnished. Women should use

eﬀective contraception during treatment and for 30 days after treatment.

Contents of the pack

VALHET ORALSOLUTION powder for oral solution:

12 grams of powder in 120 mL (with reconstituted 100 mL ﬁll volume) molded amber colored type I glass bottle with 28

mm screw type neck ﬁnish with white opaque polypropylene, ribbed, child resistant plastic caps with opening

illustrations embossed on top. The bottles come with 2 10 mLoral dosing syringes with a white opaque tip cap and clear

adapter with printed graduation marks from 1 mLto 10,0 mLand each 0,5 mLon barrel.

4.4 Special warnings and precautions for use

Mutagenicity, teratogenicity, carcinogenicity, fertility and contraception

Prior to the initiation of valganciclovir treatment, patients should be advised of the potential risks to the foetus. VALHET

ORAL SOLUTION should be considered a potential teratogen and carcinogen with the potential to cause birth defects

and cancers. It is likely that valganciclovir causes temporary or permanent inhibition of spermatogenesis (see section

4.6). Valganciclovir has the potential to cause carcinogenicity and reproductive toxicity in the long-term.

Infections and

Infestations

Severe neutropenia, anaemia, thrombocytopenia,

leukopenia, pancytopenia

Bone marrow depression, aplastic anaemia

Frequent

6 PHARMACEUTICALPARTICULARS

6.1 List of excipients

Blood and lymphatic

system disorders

Less frequent

Frequent unknown

Frequent

Anhydrous citric acid

Mannitol

Povidone

Sodium benzoate

Saccharin sodium

Puriﬁed water

Driving and using machines

VALHET ORALSOLUTIONmay make you feel dizzy, tired, sleepy, shaky or confused.

VALHET ORAL SOLUTION may impair your ability to drive and use machines. Do not drive, operate machinery, or do

anything else that could be dangerous until you know howVALHET ORALSOLUTIONaﬀects you.

Agranulocytosis, granulocytopenia

Myelosuppression

Bottle is enclosed in an outer carton until required for use.

Hypersensitivity

Anaphylactic reaction

Decreased appetite, anorexia

Immune system

disorders

Metabolism and

Severe leukopenia, neutropenia, anaemia, thrombocytopenia, pancytopenia, bone marrow depression and aplastic

anaemia have been observed in patients treated with VALHET ORAL SOLUTION (and ganciclovir). Therapy should

not be initiated if the absolute neutrophil count is less than 500 cells/µL, or the platelet count is less than 25 000/µL, or

the haemoglobin level is less than 8 g/dL.

Less frequent

Holder of Certiﬁcate of Registration

Hetero Drugs SouthAfrica (Pty) Ltd

Waterfall Corporate

Frequent

nutrition disorders

Frequent

Less frequent

Depression, anxiety, confusion, abnormal thinking

Agitation, psychotic disorder, hallucinations,

Psychiatric disorders

VALHET ORAL SOLUTION powder for oral solution contains sodium benzoate. Benzoate salt may increase jaundice

(yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).

VALHET ORAL SOLUTION should be used with caution in patients with pre-existing haematological cytopenia or a

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

It is recommended that complete blood counts and platelet counts be monitored during therapy. In patients with severe

leukopenia, neutropenia, anaemia and/or thrombocytopenia, it is recommended that treatment with haematopoietic

growth factors and/or dose interruption be considered (see section 4.2).

The bioavailability of ganciclovir from VALHET ORAL SOLUTION is up to 10-fold higher than from ganciclovir

capsules.

VALHET ORALSOLUTIONcannot be substituted for ganciclovir capsules on a one-to-one basis.

Renal impairment

In patients with impaired renal function, dosage adjustments based on creatinine clearance are required (see section

4.2).

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

ORALSOLUTIONpowder for oral solution, should be used in these patients.

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

Use with other medicines

Tutti-frutti ﬂavor 051880 AP0551 contains maize maltodextrin, ﬂavourings, INS 1520 polypropylene glycol, INS

307 c dl-alpha-tocopherol

Campus, Building No.2,

Headache, insomnia, dysgeusia, hypoaesthesia,

paraesthesia, peripheral neuropathy, dizziness (excluding

vertigo), convulsion

Tremor

Macular oedema, retinal detachment, vitreous ﬂoaters,

eye pain, visual disturbance, conjunctivitis

Ear pain

Deafness

Dysrhythmias

Hypotension, hypertension

Dyspnoea, cough

Diarrhoea, nausea, vomiting, abdominal pain, upper

abdominal pain, dyspepsia, constipation, ﬂatulence,

dysphagia,

First Floor, 74 Waterfall Drive, Midrand, 2066

Telephone number: 012 644 1220

Fax number: 012 644 1564

Nervous system

disorders

Frequent

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Powder for oral solution:24 months.

Reconstituted solution:49 days stored in a refrigerator at 2 °C – 8 °C.

3. How to take VALHET ORALSOLUTION

Do not share medicines prescribed for you with any other person.

Always take VALHET ORAL SOLUTION exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Less frequent

Frequent

e-mail address: nokuthula.n@hetero.com

Eye disorders

This leaﬂet was last revised in

23 May 2025

Frequent

Ear and labyrinth

disorders

Cardiac disorders

Vascular disorders

Respiratory, thoracic and Frequent

mediastinal disorders

Gastrointestinal

disorders

6.4 Special precautions for storage

Less frequent

Frequent

Store at or below 25 °C. Protect from light and moisture.

Bottle must be kept tightly-closed.

Reconstituted solution to be stored not longer than 49 days at 2 °C to 8 °C (see section 6.3).

The usual dose is:

Inductiontreatment of CMV retinitis

For patients with active CMV retinitis, the recommended dose is 900 mg VALHET ORAL SOLUTION twice a day for 21

days. Prolonged induction treatment may increase the risk of bone marrow toxicity.

Registration number

54/20.2.8/0271

6.5 Nature and contents of container

VALHET ORALSOLUTIONpowder for oral solution:

12 grams of powder in 120 mL(with reconstituted 100 mLﬁll volume) moulded amber coloured type I glass bottle with 28

mm screw type neck ﬁnish with white opaque polypropylene, ribbed, child resistant plastic caps with opening

illustrations embossed on top. The bottles come with 2 10 mLoral dosing syringes with a white opaque tip cap and clear

adapter with printed graduation marks from 1 mLto 10,0 mLand each 0,5 mLon barrel.

Access to the corresponding Professional Information

Hetero Drugs SouthAfrica (Pty) Ltd

Waterfall Corporate

Frequent

Maintenance treatment of CMV retinitis

Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is 900 mg VALHET

ORALSOLUTIONonce daily.

Less frequent

Frequent

Abdominal distension, mouth ulcerations, pancreatitis

Severe abnormal hepatic function, increased blood

alkaline phosphatase, increased aspartate aminotrans

ferase

VALHET ORALSOLUTIONshould not be used concomitantly with imipenem-cilastatin (see section 4.5).

Zidovudine and VALHET ORAL SOLUTION each have the potential to cause neutropenia and anaemia. Some

Campus, Building No.2,

Hepato-biliary disorders

First Floor, 74 Waterfall Drive, Midrand, 2066

Telephone number: 012 644 1220

Fax number: 012 644 1564

Bottle is enclosed in an outer carton until required for use.

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

Didanosine plasma concentrations may increase during concomitant use with VALHET ORAL SOLUTION, therefore

Less frequent

Frequent

Less frequent

Frequent

Prevention of CMV disease in solid organ transplantation

For kidney transplant patients, the recommended dose is 900 mg once daily depending on creatinine clearance (kidney

function test), starting within 10 days of transplantation until 200 days post (after)-transplantation.

For patients who have received a solid organ transplant other than the kidney, the recommended dose is 900 mg daily,

starting within 10 days of transplantation until 100 days post (after)- transplantation.

Increased alanine aminotransferase

6.6 Special precautions for disposal and other handling

Dermatitis, pruritus, rash, night sweats

Alopecia, urticaria, dry skin

Back pain, myalgia, arthralgia, muscle cramps

Skin and subcutaneous

tissue disorders

Musculoskeletal and

Since VALHET ORAL SOLUTION is considered a potential teratogen and carcinogen in humans, powder for oral

solution and reconstituted solution should be handled with caution. If a powder or solution makes direct contact with

skin, the area should be washed thoroughly with soap and water. If the solution gets into the eye, the eye should

immediately be thoroughly washed with water.

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

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

VALHET ORALSOLUTIONmay result in added toxicity (see section 4.5).

e-mail address: nokuthula.n@hetero.com

connective tissue disorders

Frequent

Less frequent

Decreased creatinine renal clearance, renal impairment

Haematuria, renal failure

Male infertility

Renal and urinary

disorders

Reproductive system

Cross-hypersensitivity

7 HOLDER OF CERTIFICATE OF REGISTRATION

Hetero Drugs SouthAfrica (Pty) Ltd

Waterfall Corporate Campus,

Building No.2, First Floor,

74 Waterfall Drive,

Midrand, 2066

Telephone number: 012 644 1220

Fax number: 012 644 1564

e-mail address: nokuthula.n@hetero.com

Due to the similarity of the chemical structure of ganciclovir and that of aciclovir and penciclovir, a cross-hypersensitivity

reaction between these drugs is possible. Caution should therefore be used when prescribing VALHET ORAL

SOLUTION to patients with known hypersensitivity to aciclovir or penciclovir, (or to their prodrugs, valaciclovir or

famciclovir respectively).

VALHET ORALSOLUTION should be taken with food. If you are unable to eat for any reason, you should still take your

dose ofVALHET ORALSOLUTIONas usual.

and breast disorders

General disorders and

administrative site

conditions

Investigations

Frequent

Fatigue, pyrexia, rigors, pain, malaise, asthenia, chest

pain, transplant rejection

Decreased weight, increased blood creatinine

Your doctor will prescribe appropriate dose according to your condition. It is important to follow the dosage strictly to

avoid overdose.

It is important that you use the syringe provided in the pack to measure your dose of VALHET ORALSOLUTION.

Your doctor will tell you how long your treatment with VALHET ORALSOLUTION will last. Do not stop treatment early. If

you have the impression that the eﬀect of VALHET ORAL SOLUTION is too strong or too weak, tell your doctor or

pharmacist.

Precautions to be taken before handling

Owing to the teratogenic character, the valganciclovir powder and reconstituted solution should be handled with

caution. Inhalation should be avoided. If the powder or solution make direct contact with skin, the area should be

washed thoroughly with soap and water. If the solution gets into the eye, the eye should be thoroughly washed with

water immediately.

C) 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 normalises within 2 to 5 days

after discontinuation of the medicine or dose reduction (see section 4.4).

8 REGISTRATION NUMBER

54/20.2.8/0271

Paediatric population

Safety and eﬃcacy in children have not been established in adequate and well controlled clinical studies (see section

4.2).

9 DATE OF FIRSTAUTHORISATION

12 September 2023

10 DATE OF REVISION OF THE TEXT

If you take more VALHET ORALSOLUTION than you should

In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or

poison centre.

Taking too much VALHET ORAL SOLUTION can cause serious side eﬀects, particularly aﬀecting your blood or

kidneys.

Thrombocytopenia

Excipients with known eﬀects

Patients with low baseline platelet counts (< 100 000/μL) have an increased risk of developing thrombocytopenia.

Patients with iatrogenic immunosuppression due to treatment with immunosuppressive medicines are at greater risk of

thrombocytopenia than patients with AIDS (see section 4.4). Severe thrombocytopenia may be associated with

potentially life-threatening bleeding.

VALHET ORALSOLUTION powder for oral solution contains sodium benzoate. Increase in bilirubinaemia following its

displacement from albumin may increase neonatal jaundice which may develop into kernicterus (non-conjugated

bilirubin deposits in the brain tissue).

23 May 2025

4.5 Interaction with other medicines and other forms of interaction

The following medicines, valaciclovir, didanosine, nelﬁnavir, ciclosporin, omeprazole and mycophenolate mofetil did

not aﬀect the permeability of valganciclovir (ratin-situ model).

VALHET ORAL SOLUTION is metabolised to ganciclovir. Therefore, medicine interactions associated with ganciclovir

will be expected forVALHET ORALSOLUTION.

Reporting of suspected adverse reactions

If you forget to take VALHET ORALSOLUTION

If you have missed your dose by only a few hours, take the missed dose as soon as you remember. If it is almost time for

your next dose, skip the missed dose and takeVALHET ORALSOLUTIONat the next regularly scheduled time.

Do nottake a double dose to make up for forgotten individual doses.

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring

of the beneﬁt/risk balance of the medicine. Health care providers are asked to report any suspected adverse drug

reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found

on SAHPRAwebsite or to the Holder of certiﬁcate of registration through the mail: pvg.cdma@heterogroups.com.

Interactions with ganciclovir

Imipenem-cilastatin

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

medicines should not be used concomitantly.

4.9 Overdose

Eﬀects when treatment with VALHET ORALSOLUTION is stopped:

You must not stop taking your medicine unless your doctor tells you to.

It is expected that an overdose of VALHET ORAL SOLUTION, could also possibly result in increased renal toxicity.

Haemodialysis and hydration may be of beneﬁt in reducing blood plasma levels in patients who receive an overdose of

VALHET ORALSOLUTION.

Probenecid

Probenecid given with oral ganciclovir may reduce renal clearance of ganciclovir (20 %) leading to statistically

4. Possible side eﬀects

VALHET ORALSOLUTIONcan have side eﬀects.

Overdose experience with IV ganciclovir:

PASIËNTINLIGTINGSBLAD VIR VALHET ORAL SOLUTION

Moenie 'n dubbele dosis drink om vir die vergete individuele dosisse op temaak nie.

PROFESSIONELE INLIGTING VIR VALHET ORAL SOLUTION

Konvulsies is aangemeld in pasiënte wat gansiklovir en imipenem-silastatien gelyktydig gebruik het. Hierdie medisyne

moet nie saam gebruik word nie.

Probenesied

Probenesied wat saam met orale gansiklovir gegee word, kan die renale opruiming van gansiklovir verlaag (20%), wat

die blootstelling aansienlik verhoog (40%). Hierdie veranderinge is in ooreenstemming met 'n meganisme van

interaksie wat mededinging vir renale tubulêre ekskresie behels. Daarom moet pasiënte wat probenesied en VALHET

ORALSOLUTIONdrink vir toksisiteit vanweë gansiklovir gemonitor word.

monitering van die voordeel/risiko-balans van die medisyne toe. Gesondheidsorgverskaﬀers word gevra om enige

vermoedelike nadelige geneesmiddelreaksies aan SAHPRA aan te meld via die Med Safety APP (Medsafety X

SAHPRA) en eReporting-platform (who-umc.org) wat op SAHPRA-webwerf gevind word of aan die houer van

registrasiesertiﬁkaat deur die pos: pvg.cdma@heterogroups.com

SKEDULERINGSTATUS

1 NAAM VAN DIE MEDISYNE

VALHETORALSOLUTION50 mg/mL(poeier vir orale oplossing)

2 KWALITATIEWEEN KWANTITATIEWESAMESTELLING

SKEDULERINGSTATUS

Effekte wanneerbehandelingmet VALHETORALSOLUTIONgestaak word

U moet nie ophou om u medisyne tedrink nie, tensy u dokter vir u sê om dit tedoen.

4.9 Oordosis

Dit word verwag dat 'n oordosis VALHET ORAL SOLUTION moontlik ook tot erger niertoksisiteit kan lei. Hemodialise

en hidrasie kan nuttig wees om vlakke in bloedplasma van pasiënte wat 'n oordosis VALHET ORAL SOLUTION

ontvang het, teverlaag.

VALHET ORAL SOLUTION 50 mg/ mL (poeier vir orale oplossing)

Valgansiklovirhidrochloried

Bewaarmiddel: natriumbensoaat 1 mg/ml.

4. Moontlikenewe-effekte

VALHETORALSOLUTIONkan newe-effekteveroorsaak.

Nie al die newe-effekte wat vir VALHET ORAL SOLUTION aangemeld is, is in hierdie blad opgeneem nie. As u

algemene gesondheidstoestand versleg of as u enige newe-effekte ervaar terwyl u VALHET ORAL SOLUTION

drink, moet u u gesondheidsorgverskaffer asseblief om advies raadpleeg.

Elke mL aangemaakte orale oplossing bevat 55,15 mg valgansiklovirhidrochloried gelykstaande aan 50 mg

valgansiklovir vry basis.

Bewaarmiddel: natriumbensoaat 1 mg/mL.

Bevat suiker (57,150 mg mannitol per mL).

Bevat versoeter (0,300 mg natriumsakkaraat per mL).

Raadpleeg afdeling 6.1 vir 'n volledige lys hulpstowwe.

3 FARMASEUTIESE VORM

VALHET ORAL SOLUTION is wit tot eﬀens geel gekleurde poeier. Die aangemaakte oplossing is 'n kleurlose tot

bruingeel helder oplossing met'nTuttiFrutti-geur.

Sidovudien

Ervaring metoordosis van IV-gansiklovir:

Toe sidovudien saam met orale gansiklovir gegee is, was daar 'n klein (17%), maar statisties beduidende styging in die

AOK van sidovudien. Daar was ook 'n tendens na laer konsentrasies van gansiklovir toe dit saam met sidovudien

gegee is, hoewel dit nie statisties betekenisvol was nie.Aangesien sowel sidovudien en gansiklovir egter die potensiaal

het om neutropenie en anemie te veroorsaak, kan dit wees dat sommige pasiënte nie die gesamentlike behandeling

teen die volle dosis kan verdra nie (sien afdeling 4.4).

Die meerderheid pasiënte het een ofmeer van die volgende newe-eﬀekte ervaar:

Bevat suiker (57,150 mg mannitol per mL)

Bevat versoeter (0,300 mg natriumsakkaraat per mL).

Hematologiese toksisiteit: pansitopenie, beenmurgonderdrukking, medullêre aplasie, leukopenie, neutropenie,

granulositopenie.

Hepatotoksisiteit: hepatitis, lewerfunksieversteuring.

Niertoksisiteit: verergering van hematurie in 'n pasiënt met bestaande swak nierfunksie, akute nierversaking en

hoë vlakke kreatinien.

Gastro-intestinale toksisiteit: buikpyn, diarree, braking.

Neurotoksisiteit: algemene bewing, stuiptrekkings.

As enige van die volgende voorkom, moet u ophou om VALHET ORALSOLUTION te drink en dadelik vir u dokter sê of

na die ongevalle-afdeling van u naaste hospitaal gaan:

Didanosien

Lees hierdiehelebladnoukeurigdeurvoordatubeginomVALHETORALSOLUTIONte drink.

Dit is bevind dat plasmakonsentrasies van didanosien konsekwent verhoog as dit saam met gansiklovir gegee word

(sowel binneaars as mondeling). Teen orale dosisse van gansiklovir van 3 en 6 g/dag is 'n styging in die AOK van

didanosien wat wissel van 84 tot 124% waargeneem. Hierdie styging kan nie deur mededinging vir renale tubulêre

sekresie verklaar word nie, aangesien daar 'n toename was in die persentasie didanosien wat uitgeskei is. Hierdie

toename kan voortspruit uit óf verhoogde biobeskikbaarheid óf laer metabolisme. Daar was geen klinies-beduidende

eﬀek op die konsentrasies van gansiklovir nie.As gevolg van die styging in plasmakonsentrasies van didanosien in die

teenwoordigheid van gansiklovir, moet pasiënte noukeurig vir toksisiteit vanweë didanosien gemonitor word (sien

afdeling 4.4).

•

Hou hierdie blad. Dit mag nodig wees dat u dit weer moet lees.

Asu nog vrae het, moet u asseblief vir u dokter, apteker, verpleegkundige ofander gesondheidsorgverskaﬀer vra.

VALHET ORAL SOLUTION is vir u persoonlik voorgeskryf en u moet nie u medisyne vir ander mense gee

nie. Dit kan hulle skaad, selfs al is hulle simptome dieselfde as u s'n.

swelling van die hande, voete, enkels, gesig, lippe en mond of keel wat probleme met sluk of asemhaling kan

veroorsaak

veluitslag ofjeuk

floutes

4 KLINIESEBESONDERHEDE

4.1 Terapeutiese indikasies

VALHETORALSOLUTIONis aangedui vir:

5 FARMAKOLOGIESEEIENSKAPPE

Hierdie is almal baie ernstige newe-effekte.As u dit ervaar, kan dit wees dat u 'n ernstige allergiese reaksie op VALHET

ORALSOLUTIONhet. Dit mag wees dat u dringende mediese aandag ofhospitalisasie nodig het.

5.1 Farmakokinetiese eienskappe

Farmakologiese klassiﬁkasie:A20.2.8.Antivirale middels

Farmakoterapeutiese groep: antivirale middels vir sistemiese gebruik, nukleosiede en nukleotiede, maar

trutranskriptaseremmers uitgesluit. ATC-kode:J05AB14

Wat inhierdiebladis

Die behandeling van retinitis vanweë sitomegalovirus (CMV) in pasiënte met verworwe

immuniteitsgebreksindroom (VIGS).

1. WatVALHETORALSOLUTIONis en waarvoor dit gebruik word

2. Watu moet weet voordat u VALHETORALSOLUTIONdrink

3. Hoe om VALHETORALSOLUTIONtedrink

4. Moontlike newe-eﬀekte

5. Hoe om VALHETORALSOLUTIONtebêre

6. Inhoud van die pak en ander inligting

Mofetielmikofenolaat

Sê dadelik vir u dokter ofgaan na die ongevalle-afdeling van u naaste hospitaal as u enige van die volgende opmerk:

Op grond van die resultate van 'n studie met enkele aanbevole orale dosisse van mofetielmikofenolaat (MMF) en

intraveneuse gansiklovir en die bekende eﬀekte van swak nierfunksie op die farmakokinetika van MMF en gansiklovir,

word verwag dat gelyktydige toediening van hierdie middels (wat die potensiaal het om vir renale tubulêre sekresie mee

te ding) tot toename in fenoliese glukuronied van mikofenolsuur (MPAG) en gansiklovirkonsentrasie sal lei. Geen

wesenlike verandering in die farmakokinetika van mikofenolsuur (MFS) word verwag nie en geen aanpassing in die

MMF-dosis is nodig nie. Vir pasiënte met swak nierfunksie wat MMF en gansiklovir saam kry, moet by die aanbevole

dosis van gansiklovir gehou en pasiënte noukeurig gemonitor word.

Die voorkoming van CMV-siekte in pasiënte met vaste orgaanoorplantings onder risiko, d.w.s. seropositiewe

skenkers en seronegatiewe ontvangers.

4.2 Dosisenmetode vantoediening

Dosis

Strengnakomingvan dosisaanbevelingsisnoodsaaklikomoordoseringte vermy.

Die biobeskikbaarheid van gansiklovir vanuit VALHET ORAL SOLUTION is tot 10 keer hoër as vanuit gansiklovir

kapsules, dus die dosering en toediening moet noukeurig gevolg word.

Die sistemiese blootstelling aan gansiklovir na toediening van 900 mg valgansiklovir orale oplossing is gelykstaande

aan 'n dosis van 900 mg valgansiklovir tablette (2 tablette van 450 mg).

Standaarddosisvir volwassenes

koors, moegheid, seer keel, geswelde limfkliere – dit kan tekens van infeksie wees as gevolg van 'n afname in die

aantal witbloedselle

Valgansiklovir is die L-valielester (progeneesmiddel) van gansiklovir. Na orale toediening word valgansiklovir vinnig en

omvattend deur ingewands- en leweresterases na gansiklovir gemetaboliseer.

Gansiklovir is 'n sintetiese analoog van 2'-deoksiguanosien en in vitro en in vivo rem dit replisering van herpesvirusse.

Menslike virusse wat in vitro sensitief is, is onder meer menslike sitomegalovirus (HCMV), herpes simplex virus-1 en -2

(HSV-1 en HSV-2), menslike herpesvirus-6, -7 en -8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster-

virus (VZV)en hepatitis B-virus (HBV).

kneusing en bloeding, wat 'n verandering in u bloedselle kan aandui

voel kortasem ofsukkel om asem tehaal (dispnee)

versteurde visie, onvermoë om in dowwe lig te sien, gedeeltelike verlies van visie, sien ligflitse, sien kolle,

sensitiwiteit vir lig, verlies van visie wat 'n losgelate retina kan aandui

inflammasie van sellulêre weefsel (sellulitis), inflammasie ofinfeksie van die niere ofblaas

‘n styging in vlakke van sommige lewerensieme, wat slegs in bloedtoetse gesien sal word

veranderings in die normale werking van die niere

depressie

doofheid

Salsitabien

1. Wat VALHETORALSOLUTIONisenwaarvoor ditgebruikword

VALHETORALSOLUTIONbehoort aan 'n groep medisyne wat werk om die groei van virusse tevoorkom.

VALHETORALSOLUTIONword gebruik:

Salsitabien het dieAOK_0-8hvan orale gansiklovir met 13% verhoog. Daar was geen statisties beduidende veranderinge

in enige van die ander bestudeerde farmakokinetiese parameters nie. Daar was ook geen kliniese relevante

veranderinge in die farmakokinetika van salsitabien in die teenwoordigheid van orale gansiklovir nie, alhoewel 'n klein

toename in die eliminasietempokonstante waargeneem is.

Sowel VALHET ORAL SOLUTION as salsitabien het die potensiaal om perifere neuropatie te veroorsaak en pasiënte

moet vir sulke eﬀekte gemoniteer word.

Stavudien

Geen statisties beduidende farmakokinetiese interaksies is waargeneem toe stavudien en orale gansiklovir in

kombinasie gegee is nie.

Trimetopriem

Trimetopriem het die renale opruiming van orale gansiklovir statisties beduidend met 16,3% verminder en dit het met 'n

statisties beduidende afname in die terminale eliminasietempo en die ooreenstemmende verlenging van 15% in die

halﬂeeftyd gepaardgegaan. Hierdie veranderinge sal egter waarskynlik nie klinies beduidend wees nie, aangesien

AOK_0-8en C_maksonaangetas is. Die enigste statisties beduidende verandering in farmakokinetiese parameters van

trimetopriem wanneer dit saam met gansiklovir toegedien is, was 'n 12% toename in C_min. Dit is egter onwaarskynlik dat

dit van kliniese belang is en geen dosisaanpassing word aanbeveel nie.

Vir antivirale aktiwiteit moet gansiklovir fosforilering na sytrifosfaatvorm ondergaan.

In CMV-geïnfekteerde selle word gansiklovir aanvanklik deur die virale proteïenkinase, pUL97, na gansiklovirmonofosfaat

gefosforileer. Verdere fosforilering deur sellulêre kinases vind plaas om gansiklovirtrifosfaat te lewer, wat dan stadig

intersellulêr gemetaboliseer word. Dit is getoon dat trifosfaatmetabolisme na die verwydering van ekstrasellulêre gansiklovir

voorkom in HSV-en HSMV-geïnfekteerde selle, methalﬂeeftye van 18 en tussen 6 en 24 uur onderskeidelik.

Aangesien fosforilering grootliks van die virale kinase afhanklik is, vind fosforilering van gansiklovir by voorkeur in

virusbesmette selle plaas.

Die statiese aktiwiteit van gansiklovir op virusse is toe teskryfaan remming van virale DNA-sintese deur:

a) gansiklovirtrifosfaat wat die inkorporering van deoksiguanosien-trifosfaat (dGTP) in DNA deur virale DNA-

polimerase mededingend rem, en

b) inkorporering van gansiklovirtrifosfaat in virale DNA wat beëindiging van verdere verlenging van virale DNA

veroorsaak ofdit baie beperk.

•

vir die behandeling van infeksies deur sitomegalovirus (SMV) van die retina van die oog van volwasse pasiënte

met verworwe immuniteitsgebreksindroom (VIGS). SMV-infeksie van die retina van die oog kan visieprobleme en

selfs blindheid veroorsaak.

om SMV-infeksies te voorkom in volwassenes en kinders wat nie met SMV besmet is nie en wat 'n

orgaanoorplanting ontvang het van iemand wat deur SMVbesmet is.

Induksiebehandelingvan CMV-retinitis

Vir pasiënte met aktiewe CMV-retinitis, is die aanbevole dosis 900 mg CMVALtwee keer per dag vir 21 dae. Langdurige

induksiebehandeling kan die risiko vir beenmurgtoksisiteit verhoog.

•

ontsteking van die pankreas (pankreatitis), waar mens erge pyn in die maag en rug kan ervaar

bloed in die urien, nierversaking

Instandhoudingsbehandelingvan CMV-retinitis

Nadat u VALHET ORAL SOLUTION gedrink het, word die valganciclovir vinnig in u liggaam verander om gansiklovir,

wat die aktiewe middel is, vry te stel. Gansiklovir verhoed die groei en die toename in getalle van 'n virus genaamd

sitomegalovirus (CMV).

Na induksiebehandeling, of vir pasiënte met onaktiewe CMV-retinitis, is die aanbevole dosis 900 mg VALHET ORAL

SOLUTION een keer per dag. Pasiënte wie se retinitis vererger kan induksiebehandeling herhaal; oorweging moet

egter gegee word aan die moontlikheid van weerstand teen virale medisyne.

Hierdie is almal ernstige newe-effekte. Dit mag wees dat u dringende mediese aandag nodig het.

Sê so gou as moontlik vir u dokter as u enige van die volgende opmerk:

Dikwels:

VoorkomingvanCMV-siekte byvasteorgaanoorplanting

Vir nieroorplantingspasiënte is die aanbevole dosis 900 mg een keer per dag, afhangende van kreatinienopruiming. Dit

begin binne 10 dae na die oorplanting tot200 dae na die oorplanting.

Virusweerstand

2. Wat umoet weet voordatuVALHETORALSOLUTIONdrink

MoenieVALHETORALSOLUTIONdrinknie:

Virale weerstand teen gansiklovir kan ná chroniese dosering met valgansiklovir ontstaan deur seleksie van mutasies in óf

die virale kinasegeen (UL97) wat verantwoordelik is vir gansiklovirmonofosforilering en/of die virale polimerasegeen

(UL54). Virusse wat mutasies in die UL97-geen bevat, is bestand teen gansiklovir alleen, terwyl virusse met mutasies in die

UL54-geen bestand is teen gansiklovir, maar kan kruisweerstand toon teenoor ander antivirale middels wat ook die virale

polimerase teiken.

swaminfeksie in die mond (orale kandidiase), infeksies wat veroorsaak word deur bakterieë ofvirusse in die bloed

geswelde maag, mondsere

diarree

‘n afname van die pigment in die bloed wat suurstof dra (anemie) -wat moegheid en uitasemheid kan veroorsaak

hoofpyn

rooi, geswelde oë (konjunktivitis), abnormale visie

probleme om teslaap

vreemde smake

•

as u hipersensitief (allergies) vir valasiklovir, gansiklovir, asiklovir, valasiklovir of enige van die ander bestanddele

van VALHETORALSOLUTIONis (gelys in afdeling 6).

as u borsvoed.

as u al ooit 'n allergiese reaksie op asiklovir of valasiklovir gehad het (wat gebruik word om virale infeksies te

behandel wat veroorsaak word deur herpes simplex, waaronder koorsblare).

Vir pasiënte wat 'n vasteorgaanoorplanting gehad het, is die aanbevole dosis 900 mg een keer per dag, vanaf binne 10

dae na die oorplanting tot100 dae na die oorplanting.

Spesiale populasies

Siklosporien

•

Daar was, gebaseer op die vergelyking van die trogkonsentrasies van siklosporien, geen bewyse dat gansiklovir die

farmakokinetika van siklosporien beïnvloed nie. Daar was egter tekens van stygings in die maksimum

serumkreatinienwaarde na aanvang van behandeling metgansiklovir.

Antivirale aktiwiteit

Die in vitro-antivirale aktiwiteit, gemeet as IC₅₀van gansiklovir teen CMV is in die orde van 0,08 μM (0,02 μg/mL) tot 14 μM

(3,5 μg/mL).

5.2 Farmakokinetiese eienskappe

Absorpsie

Valgansiklovir is 'n progeneesmiddel van gansiklovir. Dit word goed vanuit die spysverteringskanaal geabsorbeer en word

vinnig en omvattend in die dermwand en lewer na gansiklovir gemetaboliseer. Die absolute biobeskikbaarheid van

gansiklovir vanaf is valgansiklovir ongeveer 60%. Sistemiese blootstelling aan valgansiklovir is tydelik en laag.

Valgansiklovir laat sistemiese blootstelling aan gansiklovir toe, wat soortgelyk is aan dié wat bereik word met aanbevole

dosisse van intraveneuse gansiklovir.

Pasiënte met swak nierfunksie

Serumkreatinienvlakke of kreatinienopruiming moet noukeurig gemonitor word.Aanpassing van die dosis vir volwasse

pasiënte op grond van kreatinienopruiming, soos inTabel 1 hier onder, is nodig.

Kreatinienopruiming (mL/min) word metdie volgende formules vanaf serumkreatinienvlakke bereken:

Ander moontlikemedisyne-interaksies

Waarskuwings envoorsorgmaatreëls

Wees besonderversigtigmet VALHETORALSOLUTION

Toksisiteit kan versterk word wanneer gansiklovir gegee word saam met of onmiddellik voor of na ander medisyne wat

replisering van vinnig verdelende selbevolkings rem, soos in beenmurg, die kiemlaag van die vel en gastro-intestinale

mukosa of wat met swak nierfunksie verband hou (soos dapsoon, pentamidien, ﬂusitosien, vinkristien, vinblastien,

adriamisien, amfoterisien B, sulfametoksasool-trimetopriemkombinasies, nukleosiedanaloë en hidroksi-ureum).

Daarom moet hierdie middels slegs saam met valgansiklovir gebruik word as die potensiële voordele swaarder as die

potensiële risiko weeg (sien afdeling 4.4).

(140 – ouderdom)×(gewig[kg]) x konstante*

CrCl(mL/min)=

SCr [µmol/L]

•

as u 'n lae aantal witbloedselle, rooibloedselle of bloedplaatjies (klein selle wat by bloedstolling betrokke is) in

bloed het. U dokter sal voordat u begin om VALHET ORAL SOLUTION te drink bloedtoetse doen en nog

toetse sal gedoen word

terwyl u die poeier vir orale oplossing drink.

lae tassin

* Konstante = 1,23 vir mans en 1,04 vir vroue (0,85 x 1,23 = 1,04)

Die Suid-Afrikaanse Nefrologie Vereniging beveel aan om bogenoemde formule te vereenvoudig deur die konstante

van 1,23 vir mans weg te laat.

prikkelende oftintelende vel

gevoelloosheid in die hande ofvoete

duiseligheid

toevalle (stuiptrekkings)

oogpyn, swelling binne die oog

oorpyn

hoes

voel naar (naarheid) en bring op (braking), maagpyn, hardlywigheid, winde, slegte spysvertering, probleme om te

sluk

Ander antiretrovirale middels

Sitochroom P450 isoënsieme speel geen rol in die farmakokinetika van gansiklovir nie. As gevolg hiervan word geen

farmakokinetiese interaksies metproteaseremmers en nie-nukleosied trutranskriptaseremmers verwag nie.

(140 – ouderdom)×(gewig [kg]) x 0,85 (indien vroulik)

•

as u radioterapie of hemodialise ondergaan. As u dokter besluit om VALHET ORAL SOLUTION vir u te gee,

CrCl(mL/min)=

SCr [µmol/L]

Die AOK₂₄en C_maksvan valgansiklovir is ongeveer 1% en 3% van dié van gansiklovir, onderskeidelik. Ter vergelyking is die

biobeskikbaarheid van gansiklovir na toediening van 1 000 mg orale gansiklovir (as kapsules) 6 -8%.

moet u bloed gereeld

nagegaan word.

as u 'n probleem met u niere het. U dokter sal dalk 'n laer dosis vir u moet voorskryf en moet dalk u bloed

CrCl= kreatinienopruiming

SCr= kreatinienvlakke in die serum

4.6 Fertiliteit, swangerskap enborsvoeding

Voorbehoeding in mans en vroue

As gevolg van die moontlikheid vir voortplantingstoksisiteit en teratogenisiteit, moet vroue van vrugbare potensiaal

aangeraai word om tydens en vir ten minste 30 dae na behandeling eﬀektiewe kontrasepsie te gebruik. Manlike

pasiënte word aangeraai om tydens en vir ten minste 90 dae na die staking van behandeling met valgansiklovir

versperrende kontrasepsie tegebruik, tensy dit seker is dat die vroulike maat nie 'n risiko het omswanger teraak nie.

Valgansiklovirinpasiënte met MIV, CMV

gereeld

Sistemiese blootstelling van pasiënte met MIV, CMV na twee keer daaglikse toediening van gansiklovir en valgansiklovir vir

een week is:

Tabel2:

Tabel 1: Dosis van VALHET ORAL SOLUTION orale oplossing vir niergestremde pasiënte

CrCl (mL/min)

tydens behandeling kontroleer.

Induksiedosis van VALHET ORAL SOLUTION Onderhouds-/voorkomingsdosis van

orale oplossing

as u nou gansiklovirkapsules drink en u dokter wil hê dat u na VALHET ORAL SOLUTION poeier vir orale

oplossing oorskakel. Dit

is belangrik dat u nie meer as die voorgeskrewe dosis van u dokter drink nie, anders kan u 'n oordosis kry.

VALHET ORAL SOLUTION kan moontlik geboortedefekte veroorsaak. As u 'n vrou is en swanger kan raak,

moet u tydens u

behandeling en vir 30 dae nadat die behandeling geëindig het, eﬀektiewe voorbehoeding gebruik. Mans moet

aangeraai word om tydens behandeling, en vir 90 dae na behandeling 'n kondoom te gebruik.

VALHET ORAL SOLUTION poeier vir orale oplossing en die aangemaakte oplossing moet versigtig hanteer

word. As die poeier

of oplossing direk met die vel in aanraking kom, moet die area deeglik met seep en water gewas word. As die

oplossing in die oë kom, moet die oog onmiddellik deeglik met water gewas word.

VALHET ORAL SOLUTION orale oplossing

≥ 60

900 mg twee keer per dag

450 mg twee keer per dag

450 mg een keer per dag

225 mg een keer per dag

200 mg (3 x weekliks na dialise)

900 mg een keer per dag

450 mg een keer per dag

225 mg een keer per dag

125 mg een keer per dag

100 mg (3 x weekliks na dialise)

Parameter

Valgansiklovir (900 mg, een keer per dag)

n = 25

Gansiklovir

(5 mg/kg, iv)

n=18

ontsteekte vel, jeuk, sweet in die nag, haarverlies (alopesie)

rugpyn, pyn in die spiere ofgewrigte, stywe spiere, spierkrampe

verlies aan eetlus (anoreksie) en gewigsverlies

moegheid, koors, pyn, energieverlies, algemene ongesteldheid

voel angstig, verward, metongewone gedagtes

pyn in die borskas

Swangerskap

VALHETORALSOLUTIONmoet nie tydens swangerskap gebruik word nie.

Die veiligheid van VALHET ORAL SOLUTION vir gebruik deur swanger vroue is nie bepaal nie. Die aktiewe

metaboliet, gansiklovir, beweeg maklik oor die menslike plasenta. Gebaseer op die farmakologiese

werkingsmeganisme en reproduktiewe toksisiteit wat in dierestudies met gansiklovir waargeneem is, is daar 'n

teoretiese risiko van teratogenisiteit by mense.

40 – 59

25 – 39

10 – 24

< 10

Gansiklovir

32,8 ± 10.1

6,7 ± 2,1

Valgansiklovir

0,37 ± 0,22

0,18 ± 0,06

AOK (0 – 12 h) (µg.h/mL)

C_maks(µg/mL)

28,0 ± 9,0

10,4 ± 4,9

•

Pasiënte ophemodialise

'n Dosisaanpassing is nodig vir pasiënte op hemodialise (CrCl < 10 mL/min) en 'n dosisaanbeveling vir VALHET ORAL

SOLUTION-poeier vir orale oplossing word in die bostaande tabel gegee.

Dit is getoon dat die eﬀektiwiteit van gansiklovir om die tyd tot progressie van CMV-retinitis te verleng met sistemiese

blootstelling (AOK)korreleer.

Borsvoeding

Dit is onbekend of gansiklovir in menslike borsmelk uitgeskei word, maar die moontlikheid dat gansiklovir in die

borsmelk uitgeskei word en ernstige nadelige reaksies in die sogende baba kan veroorsaak, kan nie uitgesluit word nie.

Data van dierestudies dui daarop dat gansiklovir in die melk van lakterende rotte uitgeskei word. Daarom moet

borsvoeding tydens behandeling metvalganciclovir gestaak word (sien afdeling 4.3).

lae bloeddruk, wat kan veroorsaak dat mens lighoofdig offlou voel

Valgansiklovirinpasiënte met vasteorgaanoorplantings:

Kinders enadolessente

Die veiligheid en eﬀektiwiteit van VALHETORALSOLUTIONvir kinders is nie bepaal nie.

Pasiënte met erge leukopenie, neutropenie, anemie, trombositopenieenpansitopenie

Erge leukopenie, neutropenie, anemie, trombositopenie en pansitopenie, beenmurgonderdrukking en aplastiese

anemie is waargeneem in pasiënte wat met VALHET ORAL SOLUTION (en gansiklovir) behandel is. Behandeling

Gelykvlak sistemiese blootstelling van pasiënte met vasteorgaanoorplantings aan gansiklovir na die daaglikse orale

toediening van gansiklovir en valgansiklovir is:

Tabel3:

Minder dikwels:

veranderinge in normale hartklop

bewerasie ofbewing

jeukerige uitslag ofswellings (urtikarie), droë vel

‘n styging in vlakke van 'n lewerensiem genaamd alanienaminotransferase (wat slegs in bloedtoetse gesien sal

word)

Vrugbaarheid

Andermedisyne enVALHETORALSOLUTION

'n Kliniese studie met nieroorplantingspasiënte wat valgansiklovir vir tot 200 dae vir CMV-proﬁlakse ontvang het, het 'n

impak van valgansiklovir op spermatogenese getoon, met lae spermdigtheid en beweeglikheid gemeet na voltooiing

van behandeling. Hierdie eﬀek blyk omkeerbaar te wees en ongeveer ses maande na die staking van valgansiklovir is

die gemiddelde spermdigtheid en beweeglikheid herstel tot vlakke wat vergelykbaar is met dié wat in die onbehandelde

kontroles waargeneem is.

Parameter

Gansiklovir

(1000 mg drie keer per dag)

n=82

Valgansiklovir

(900 mg een keer per dag)

n=161

Sê altyd vir

tradisionele medisyne). Gebruik van VALHET ORAL SOLUTION saam met hierdie medisyne kan ongewensde

gesondheidsorgverskaﬀer as

enige ander medisyne gebruik (waaronder alle aanvullende of

moet nie begin word as die absolute neutroﬁeltelling minder is as 500 selle/μL, of as die bloedplaatjietelling minder is as

25000/μL, ofdie hemoglobienvlak laer as 8 g/dLis nie (sien afdeling 4.4)

interaksies veroorsaak. Raadpleeg u dokter, apteker ofander gesondheidspraktisyn asseblief om raad.

Gansiklovir

Bejaardes

Die veiligheid en eﬀektiwiteit is nie bepaal nie.

AOK (0 – 24 h) (µg.h/mL)

C_maks(µg/mL)

28,0 ± 10,9

1,4 ± 0,5

46,3 ± 15,2

5,3 ± 1,5

Sê vir u dokter indien u reeds medisyne gebruik wat die volgende bevat:

• Imipenem-silastatien ('n antibiotikum). Gebruik hiervan saam met VALHET ORAL SOLUTION kan

stuiptrekkings (konvulsies) veroorsaak.

ongewone veranderinge in gemoed en gedrag, verloor kontak met die werklikheid, soos om stemme te hoor of

dinge tesien wat nie daar is nie, voel omgekrap

onvrugbaarheid by mans

In dierestudies het gansiklovir vrugbaarheid in manlike en vroulike muise verswak en het getoon dat dit

spermatogenese onderdruk en testikelatroﬁe in muise, rotte en honde veroorsaak teen dosisse wat as klinies relevant

beskou word.

Pediatriese populasie

Die veiligheid en eﬀektiwiteit is nog nie metvoldoende en goedgekontroleerde studies bepaal nie.

Die sistemiese blootstelling van ontvangers van hart-, nier- of leweroorplantings aan gansiklovir was soortgelyk na

orale toediening van valgansiklovir volgens die doseeralgoritme van nierfunksie.

Na toediening van valgansiklovir as 'n orale oplossing, is ekwivalente sistemiese blootstelling aan gansiklovir verkry

vergeleke metdie tabletformulering.

•

Sidovudien, didanosien, lamivudien, tenofovir, abakavir, emtrisitabien of soortgelyke tipes medisyne wat gebruik

word om VIGStebehandel. U dokter kan die dosis van didanosien verlaag as dit moet gebruik

Probenesied ('n middel teen jig). As probenesied en VALHET ORAL SOLUTION op dieselfde tyd gedrink

word, kan dit die hoeveelheid gansiklovir in u bloed verhoog.

Mofetielmikofenolaat (gebruik na orgaanoorplantings).

Vinkristien, vinblastien, adriamisien, hidroksi-ureum ofsoortgelyke tipes middels om kanker tebehandel.

Trimetopriem, trimetopriem/sulfakombinasies en dapsoon (antibiotika).

Pentamidien (medisyne om parasiet- oflonginfeksies tebehandel).

Flusitosien ofamfoterisien B(antifungusmiddels).

Gebaseer op kliniese en nie-kliniese studies, word dit as waarskynlik beskou dat gansiklovir (en valganciclovir) tydelike

ofpermanente onderdrukking van menslike spermatogenese kan veroorsaak (sien afdeling 4.4).

Metodevantoediening

VALHETORALSOLUTIONword oraal toegedien en moet saam metkos gedrink word.

As u enige newe-effekte opmerk wat nie in hierdie blad genoem word nie, moet u u dokter of apteker asseblief in kennis

stel.

4.7 Eﬀekopvermoë om'nvoertuigte bestuurenmasjiene te gebruik

Voedsel

VALHETORALSOLUTION, poeiervir orale oplossing, voorbereidingvan oplossing

1. Meet 91 mLgesuiwerde water in 'n maatsilinder af.

2. Gooi die suiwer water in die bottel. Skud die toe bottel totdatdie poeier opgelos is.

3. Verwyder die kindbestande doppie en druk die bottel se koppelstuk in die nek van die bottel.

4. Maak die bottel styfmetdie kindbestande doppie toe.

•

Konvulsies, sedasie, duiseligheid, ataksie en/of verwardheid is met die gebruik van valganciclovir en/of gansiklovir

aangemeld.As dit voorkom, kan sulke eﬀekte die take beïnvloed wat waaksaamheid vereis waaronder die vermoë van

die pasiënt om 'n voertuig tebestuur en masjinerie tehanteer.

Toe valgansiklovir teen die aanbevole dosis van 900 mg saam met kos gegee is, is verhogings gesien in beide

gemiddeldeAOK₂₄(± 30%) en gemiddelde C_maks-waardes (± 14%) van gansiklovir; dit word aanbeveel dat valgansiklovir

saam metkos gegee word.

Aanmeldvan newe-effekte

As jy newe-effekte kry, praat met jou dokter, apteker of verpleegster. Jy kan ook newe-effekte aan SAHPRArapporteer

via die Med SafetyAPP(Medsafety X SAHPRA) en eReporting platform (who-umc.org) gevind op SAHPRAwebwerf of

aan die Houer van sertifikaat van registrasie deur die pos: pvg.cdma@heterogroups.com. Deur newe-effekte aan te

meld, kan jy help om meer inligting teverskaf oor die veiligheid van VALHETORALSOLUTION.

Verspreiding

Plasmaproteïenbinding van gansiklovir oor konsentrasies van 0,5 en 51 μg/mL was 1– 2%. Die volume van

verspreiding van gansiklovir by gelykvlakke na IV-toediening was 0,680 ±0,161 L/kg.

4.8 Ongewensdeeﬀekte

a) Opsommingvandieveiligheidsproﬁel

Valgansiklovir is 'n progeneesmiddel van gansiklovir. Dit word na orale toediening vinnig na gansiklovir omgeskakel. Dit

word dus verwag dat die newe-eﬀekte vanweë die gebruik van gansiklovir ook met toediening van valganciclovir gesien

sal word.

Al die ongewenste eﬀekte van valgansiklovir wat gesien is, is voorheen met gansiklovir waargeneem. Die mees

algemene negatiewe reaksies wat na toediening van valgansiklovir aan volwassenes aangemeld is, was neutropenie,

anemie en diarree.

Valgansiklovir hou 'n laer risiko vir diarree in in vergelyking metintraveneuse gansiklovir.

Erge neutropenie (< 500 ANC/µL) is meer dikwels waargeneem in pasiënte met CMV-retinitis wat behandeling met

valgansiklovir gekry het as in pasiënte metvasteorgaanoorplantings wat valgansiklovir ontvang het.

Vir verdere instruksies oor die hantering van VALHETORALSOLUTION, sien afdeling 6.6.

Biotransformasie

5. Hoe omVALHETORALSOLUTIONte bêre

Swangerskap, borsvoedingenvrugbaarheid

As u swanger is of borsvoed, dink dat u dalk swanger kan wees of beplan om 'n baba te hê, moet u u dokter, apteker of

ander gesondheidsorgverskaﬀer asseblief om advies raadpleeg voordat u VALHETORALSOLUTIONdrink.

Valgansiklovir word vinnig en omvattend na gansiklovir gemetaboliseer, en geen ander metaboliete is waargeneem

nie. Geen metaboliet van oraal toegediende radio-gemerkte gansiklovir (1 000 mg enkeldosis) het meer as 1 - 2%

bedra van die radioaktiwiteit wat in die feses en urien herwin is nie.

•

Bêre by ofonder 25 ºC.

4.3 Kontra-indikasies

Die aangemaakte oplossing moet nie vir langer as 49 dae by 2 °Ctot8 °Cgestoor word nie.

Beskerm teen lig en vog.

Die bottel moet goed toe gehou word.

Hou die bottel in die karton totdatdit vir gebruik benodig word.

Hou alle medisyne buite bereik van kinders.

Moenie in 'n badkamer bêre nie.

Moenie na die vervaldatum op die etiket/karton/bottel gebruik nie.

Gee alle ongebruikte medisyne terug aan u apteker.

Ongebruikte medisyne moet nie in dreinering- ofrioolstelsels (bv. toilette) gegooi word nie.

VALHET ORAL SOLUTION is teenaangedui vir pasiënte met hipersensitiwiteit vir valganciclovir, gansiklovir of

vir enige van die hulpstowwe in afdeling 6.1 gelys

As gevolg van die ooreenkomste in die chemiese struktuur van VALHET ORAL SOLUTION en dié van

asiklovir en valasiklovir is 'n kruis-hipersensitiwiteitsreaksie tussen hierdie middels moontlik.

VALHETORALSOLUTIONis teenaangedui tydens borsvoeding (sien afdeling 4.6)

Uitskeiding

Die hoofroete van uitskeiding van valgansiklovir as gansiklovir is deur glomerulêre ﬁltrasie en aktiewe tubulêre sekresie

in die niere. Renale opruiming bedra 81,5% ± 22% van die totale opruiming van valgansiklovir. Die halﬂeeftyd van

gansiklovir vanaf valgansiklovir is 4,1 ±0,9 uur in MIV-en CMV-seropositiewe pasiënte.

Swangerskap

VALHET ORAL SOLUTION moet nie aan swanger vroue gegee word nie, want dit kan moontlik lei tot die verlies

vandiebabaoftotdiegeboortevan 'nmisvormde babaoftotproblemeindiebabanageboorte.

Farmakokinetika inspesiale populasies

Pasiënte met swak nierfunksie

Afname in nierfunksie het gelei tot die verlaagde opruiming van gansiklovir vanaf valgansiklovir met 'n verlenging in

terminale halﬂeeftyd. Daarom is geen aanpassing in die dosis vir bejaarde pasiënte nodig nie (sien afdeling 4.2).

Hemodialise

Vir pasiënte wat hemodialise ontvang (CrCl <10 mL/min), word 50 mg/mL poeier vir orale oplossing egter aanbeveel

om 'n geïndividualiseerde dosis tegee (sien afdeling 4.2).

Pasiënte met swak lewerfunksie

Die farmakokinetika van valgansiklovir in geskikte ontvangers van leweroorplantings is in een oop vierrigting

oorkruisstudie ondersoek. Die absolute biobeskikbaarheid van gansiklovir van valgansiklovir na 'n enkele dosis 900 mg

valgansiklovir onder gevoede toestande was ongeveer 60%, in ooreenstemming met die beramings wat in ander

pasiëntbevolkings verkry is. Die AOK_0-24van gansiklovir was vergelykbaar met dié wat met 5 mg/kg gansiklovir IV in

ontvangers van leweroorplantings verkry is.

6 FARMASEUTIESE BESONDERHEDE

6.1 Lys vanhulpstowwe

4.4 Spesiale waarskuwingsenvoorsorgmaatreëls vir gebruik

Mutagenisiteit, teratogenisiteit, karsinogenisiteit, vrugbaarheidenvoorbehoeding

Voor die aanvang van behandeling met valgansiklovir moet pasiënte ingelig word oor die potensiële risiko's vir die

fetus. VALHET ORAL SOLUTION moet as 'n potensiële teratogeen en karsinogeen in mense beskou word met die

potensiaal om geboortedefekte en kanker te veroorsaak. Dit is waarskynlik dat valgansiklovir tydelike of permanente

onderdrukking van spermatogenese veroorsaak (sien afdeling 4.6). Valgansiklovir het die potensiaal om oor die

langtermyn karsinogenisiteit en reproduktiewe toksisiteit teveroorsaak.

b) Getabuleerde opsommingvan nadeligereaksies

Orgaanstelsel

Borsvoeding

U moet nie VALHET ORAL SOLUTION drink as u swanger is of borsvoed nie. As u dokter wil hê dat u met VALHET

ORALSOLUTIONmoet begin, moet u ophou borsvoed voordat u u orale oplossing begin drink.

Frekwensie

Dikwels:

Nadelige reaksie

Orale kandidiase, sepsis (bakteremie, viremie), sellulitis,

urienweginfeksie, boonstelugweginfeksie

Infeksies en infestasies

Vrugbaarheid

Erge neutropenie, anemie, trombositopenie,

leukopenie, pansitopenie

Beenmurgonderdrukking, aplastiese anemie

Agranulositose, granulositopenie

Hipersensitiwiteit

Anaﬁlaktiese reaksie

Swak eetlus, anoreksie

Dikwels:

6. Inhoudvan diepak enander inligting

Wat VALHETORALSOLUTIONbevat

Dit is ook uiters belangrik dat sowel mans as vroue van vrugbare ouderdom eﬀektiewe voorbehoeding gebruik

wanneer VALHET ORAL SOLUTION gedrink word. As u advies oor voorbehoeding nodig het, moet u u dokter vra

voordat u VALHET ORALSOLUTION drink. Mans wie se maats swanger kan word, moet kondome gebruik terwyl hulle

VALHET ORAL SOLUTION drink en hulle moet vir 90 dae nadat die behandeling afgehandel is kondome bly gebruik.

Vroue moet eﬀektiewe voorbehoeding tydens behandeling en vir minstens 30 dae na behandeling gebruik.

Versteurings van

die bloed en limfstelsel

Minder dikwels

Frekwensie onbekend

Dikwels

Beenmurgonderdrukking

•

Die aktiewe bestanddeel is valgansiklovirhidrochloried.

Erge leukopenie, neutropenie, anemie, trombositopenie en pansitopenie, beenmurgonderdrukking en aplastiese

anemie is waargeneem in pasiënte wat met VALHET ORAL SOLUTION (en gansiklovir) behandel is. Behandeling

moet nie begin word as die absolute neutroﬁeltelling minder is as 500 selle/μL, of as die bloedplaatjietelling minder is as

25000/μL, ofdie hemoglobienvlak laer as 8 g/dLis nie (sien afdeling 4.4)

•

Die ander bestanddele is watervrye sitroensuur, mannitol, povidoon, natriumbensoaat, natriumsakkaraat,

gesuiwerde water, Tutti Frutti-geursel 051880 AP0551, bevat mieliemaltodekstrien, geurmiddels, INS 1520

polipropileenglikol, INS307 cdl-alfa-tokoferol.

Versteurings van

die immuunstelsel

Versteurings in

Minder dikwels

Motorbestuurengebruikvan masjinerie

VALHETORALSOLUTIONkan u duiselig, moeg, vaak, wankelrig ofverward laat voel.

VALHET ORAL SOLUTION kan u vermoë om 'n voertuig te bestuur of masjinerie te gebruik, aantas. Totdat u weet hoe

VALHET ORAL SOLUTION u aﬀekteer, moet u nie 'n voertuig bestuur, masjinerie hanteer of enigiets doen wat

gevaarlik kan wees nie.

Dikwels

VALHET ORAL SOLUTION moet versigtig gebruik word deur pasiënte met reeds bestaande hematologiese sitopenie

of'n geskiedenis van hematologiese sitopenie vanweë geneesmiddels en deur pasiënte wat bestraling kry.

metabolisme en voeding

HoeVALHETORALSOLUTIONlyk endieinhoudvan diepakkie

VALHET ORAL SOLUTION is wit tot effens geel gekleurde poeier. Die aangemaakte oplossing is 'n kleurlose tot

bruingeel helder oplossing met'nTuttiFruttigeur.

Watervrye sitroensuur

Mannitol

Depressie, angs, verwardheid, abnormale denke

Dikwels

Minder dikwels

Psigiatriese versteurings

Agitasie, psigotiese versteuring, hallusinasies

Hoofpyn, slaaploosheid, disgeusie, hipestesie,

parestesie, perifere neuropatie, duiseligheid (vertigo

uitgesluit,, stuiptrekkings

Dit word aanbeveel dat volledige bloedtellings en bloedplaatjietellings tydens behandeling gemoniteer word. Vir

pasiënte met ernstige leukopenie, neutropenie, anemie en/of trombositopenie, word aanbeveel dat behandeling met

hematopoiëtiese groeifaktore en/of onderbreking van die dosis oorweeg word (sien afdeling 4.2).

Povidoon

Natriumbensoaat

Versteurings van

die senustelsel

Dikwels

Natriumsakkaraat

Gesuiwerde water

Inhoudvan dieverpakking

VALHETORALEOPLOSSING

12 gram poeier in 'n gevormde amberkleurige bottel van tipe I glas van 120 mL (met gerekonstitueerde 100 mL

vulvolume) met skroeftipe nek van 28 mm met wit ondeursigtige geribde, kindbestande prop van polipropileenplastiek,

met illustrasies om oop te maak in reliëf bo-op gedruk. Die bottels kom met 2 orale doseerspuite van 10 ml, elk met 'n wit

ondeursigtige puntdop en deursigtige koppelstuk met gedrukte gradueringsmerke van 1 ml tot 10,0 ml in eenhede van

0,5 ml op die buis.

VALHET ORAL SOLUTION poeier vir orale oplossing bevat natriumbensoaat. Bensoaatsout kan geelsug (geel

verkleuring van die vel en oë) in pasgebore babas (tot4 weke oud) veroorsaak.

Die biobeskikbaarheid van gansiklovir vanaf VALHET ORAL SOLUTION is tot 10 keer hoër as van

gansiklovirkapsules.

VALHETORALSOLUTIONkan nie gansiklovirkapsules op 'n een-tot-een-basis vervang nie.

Swak nierfunksie

Aanpassings in die dosis gebaseer op kreatinienopruiming is nodig vir pasiënte met swak nierfunksie (sien afdeling

4.2).

Geen aanbeveling oor die dosis kan vir pasiënte op hemodialise (CrCl <10 mL/min) gemaak word nie. CYVALpoeier vir

orale oplossing moet vir hierdie pasiënte gebruik word.

Konvulsies is aangemeld in pasiënte wat gansiklovir en imipenem-silastatien gelyktydig gebruik het.

Minder dikwels

Dikwels

Bewerasie

Makulêre edeem, retinaloslating, drywers in die

glasliggaam, oogpyn, versteurings in visie, konjunktivitis

Tutti Frutti-geursel 051880 AP0551, bevat mieliemaltodekstrien, geurmiddels, INS 1520 polipropileenglikol, INS

307 cdl-alfa-tokoferol

Oogversteurings

6.2 Onverenigbaarhede

Nie toepaslik nie

3. Hoe omVALHETORALSOLUTIONte drink

Moenie medisyne wat vir u voorgeskryf is vir enige ander persoon gee nie.

Drink VALHET ORAL SOLUTION altyd presies soos wat u dokter of apteker vir u gesê het. Raadpleeg u dokter of

apteker as u nie seker is nie.

Dikwels

Oorpyn

Doofheid

Disritmie

hipotensie/hipertensie

Dispnee, hoes

Versteurings van die

ore en labirint

Hartversteurings

Vaskulêre versteurings

Respiratoriese,

toragiese en mediastinale

versteurings

Minder dikwels

Dikwels

6.3 Raklewe

Poeier vir orale oplossing:24 maande.

Aangemaakte oplossing:49 dae in 'n yskas by 2 tot8 ºC.

Die bottel is in 'n karton totdatdit benodig word.

Dikwels

6.4 Spesiale voorsorgmaatreëls vir bewaring

Die gewone dosis is:

Induksiebehandelingvan CMV-retinitis

Vir pasiënte met aktiewe CMV-retinitis, is die aanbevole dosis 900 mg VALHET ORAL SOLUTION twee keer per dag

vir 21 dae. Langdurige induksiebehandeling kan die risiko vir beenmurgtoksisiteit verhoog.

Bêre by ofonder 25 °C. Beskerm teen lig en vog.

Die bottel moet goed toe gehou word.

Die aangemaakte oplossing moet nie vir langer as 49 dae by 2 °Ctot8 °Cgestoor word nie (sien afdeling 6.3).

Houervan dieregistrasiesertifikaat

Hetero Drugs SouthAfrica (Edms) Bpk

Waterfall Corporate Campus

Gebruiksaam met ander medisyne

VALHETORALSOLUTIONmoet nie saam metaliskiren gebruik word nie (sien afdeling 4.5).

Sidovudien en VALHET ORAL SOLUTION het elk die potensiaal om neutropenie en bloedarmoede te veroorsaak.

Sommige pasiënte sal gelyktydige behandeling teen die volle dosisse moontlik nie verdra nie (sien afdeling 4.5).

Diarree, naarheid, braking, buikpyn, boonste buikpyn,

slegte spysvertering, hardlywigheid, winderigheid,

disfagie,

Abdominale distensie, mondsere, pankreatitis

Erge abnormale lewerfunksie, hoër vlakke alkaliese

fosfatase in die bloed, hoër vlakke aspartaat-aminotran

sferase

Gastro-intestinale

versteurings

Dikwels

6.5Aard eninhoudvandiehouer

VALHETORALSOLUTIONpoeiervir orale oplossing

12 gram poeier in 'n gevormde amberkleurige bottel van tipe I glas van 120 mL (met gerekonstitueerde 100 mL

vulvolume) met skroeftipe nek van 28 mm met wit ondeursigtige geribde, kindbestande prop van polipropileenplastiek,

met illustrasies om oop te maak in reliëf bo-op gedruk. Die bottels kom met 2 orale doseerspuite van 10 mL, elk met 'n

wit ondeursigtige puntdop en deursigtige koppelstuk met gedrukte gradueringsmerke van 1 mLtot 10,0 mLin eenhede

van 0,5 mLop die buis.

Die bottel is in 'n karton totdatdit benodig word.

6.6 Spesiale voorsorgmaatreëls vir wegdoeningenanderhantering

Aangesien VALHET ORAL SOLUTION as 'n moontlike teratogeen en karsinogeen in mense beskou word, moet die

poeier vir orale oplossing en aangemaakte oplossing versigtig hanteer word.As die poeier of oplossing direk met die vel

in aanraking kom, moet die area deeglik met seep en water gewas word.As die oplossing in die oog kom, moet die oog

onmiddellik deeglik metwater gewas word.

7 HOUER VAN DIEREGISTRASIESERTIFIKAAT

Hetero Drugs SouthAfrica (Edms) Bpk

Waterfall Corporate Campus

Gebou No. 2, Eerste Vloer, Waterfallrylaan 74,

Midrand, 2066

Telefoonnommer: 012 644 1220

Faksnommer: 012 644 1564

e-posadres: nokuthula.n@hetero.com

Gebou No.2

Minder dikwels

Dikwels

Eerste Vloer, Waterfallrylaan 74, Midrand, 2066

Telefoonnommer: 012 644 1220

Faksnommer: 012 644 1564

Instandhoudingsbehandelingvan CMV-retinitis

Na induksiebehandeling, of vir pasiënte met onaktiewe CMV-retinitis, is die aanbevole dosis 900 mg VALHET ORAL

SOLUTIONeen keer per dag.

Hepatobiliêre versteurings

Die plasmakonsentrasies van didanosien kan tydens gebruik saam met VALHET ORAL SOLUTION styg, en daarom

moet pasiënte deeglik vir toksisiteit vanweë didanosien gemonitor word (sien afdeling 4.5).

Gebruik van ander medisyne wat beenmurg onderdruk of wat met swak nierfunksie gepaardgaan saam met VALHET

ORALSOLUTIONkan totversterking van toksisiteit lei (sien afdeling 4.5).

Minder dikwels

Dikwels

Minder dikwels

Dikwels

Styging in vlakke van alanienaminotransferase

Dermatitis, pruritus, uitslag, nagsweet

Alopesie, urtikarie, droë vel

e-posadres: nokuthula.n@hetero.com

Versteurings van die vel

en subkutane weefsel

Versteurings van die

muskuloskeletale stelsel

en van bindweefsel

Voorkomingvan CMV-siekte byvasteorgaanoorplanting

Vir nieroorplantingspasiënte is die aanbevole dosis 900 mg een keer per dag, afhangende van kreatinienopruiming

(nierfunksie) vanaf binne 10 dae na die oorplanting tot200 dae na die oorplanting.

Vir pasiënte wat 'n vasteorgaanoorplanting gehad het, is die aanbevole dosis 900 mg een keer per dag, vanaf binne

10 dae na die oorplanting tot100 dae na die oorplanting.

Kruis-hipersensitiwiteit

Hierdie bladislaas hersien in

23 Mei 2025

Rugpyn, mialgie, artralgie, spierkrampe

As gevolg van die ooreenkomste in die chemiese struktuur van VALHET ORAL SOLUTION en dié van asiklovir en

valasiklovir is 'n kruis-hipersensitiwiteitsreaksie tussen hierdie middels moontlik. Wees dus versigtig wanneer VALHET

ORALSOLUTION voorgeskryf word aan pasiënte met 'n bekende hipersensitiwiteit vir asiklovir of pensiklovir (of vir hul

progeneesmiddels, valasiklovir offamsiklovir, onderskeidelik).

Dikwels

Minder dikwels

Stadige kreatinienopruiming, nierversaking

Hematurie, nierversaking

Registrasienommer

54/20.2.8/0271

Versteurings van die

niere en urienweg

Voorsorgmaatreëls voorhantering

VALHET ORAL SOLUTION moet saam met voedsel gedrink word. As u om watter rede ook al nie kan eet nie, moet u

steeds u dosis VALHETORALSOLUTIONsoos gewoonlik drink.

Versteurings in die

voortplantingstelsel en

borste

Algemene versteurings en

versteurings by die plek

van toediening

As gevolg van die teratogene karakter daarvan, moet die VALHET ORAL SOLUTION poeier en aangemaakte

oplossing versigtig hanteer word. Inaseming moet vermy word.As die poeier of oplossing direk met die vel in aanraking

kom, moet die area deeglik met seep en water gewas word. As die oplossing in die oë kom, moet die oog onmiddellik

deeglik metwater gewas word.

Minder dikwels

Manlike onvrugbaarheid

Toegangtotdietoepaslike professioneleinligting

Hetero Drugs SouthAfrica (Edms) Bpk

Waterfall Corporate Campus,

Gebou No. 2, Eerste Vloer, Waterfallrylaan 74,

Midrand, 2066

Telefoonnommer: 012 644 1220

Faksnommer: 012 644 1564

e-posadres: nokuthula.n@hetero.com

U dokter sal die geskikte dosis volgens u toestand voorskryf. Dit is belangrik om die dosis streng te volg om oordosering

tevoorkom.

Dit is belangrik dat u die spuit wat in die verpakking verskaf word gebruik om u dosis VALHET ORAL SOLUTION af te

Moegheid, koors, kouekoors, pyn, malaise, astenie,

borspyn, verwerping van oorplanting

Dikwels

Pediatriese populasie

Die veiligheid en eﬀektiwiteit in kinders is nog nie met voldoende en goedgekontroleerde kliniese studies bepaal nie

(sien afdeling 4.2).

Dikwels

Laboratoriumtoetse

Laer gewig, hoë vlakke kreatinien in die bloed

meet.

U dokter sal vir u sê hoe lank u behandeling met VALHET ORAL SOLUTION sal duur. U moet nie voortydig ophou om

dit te gebruik nie. Sê vir u dokter of apteker as u die indruk het dat die eﬀek van VALHET ORALSOLUTION te sterk of te

swak is.

c) Beskrywing van spesiﬁeke nadeligereaksies

Neutropenie

Die risiko vir neutropenie is nie op grond van die aantal neutroﬁele voor behandeling voorspelbaar nie. Neutropenie

kom gewoonlik tydens die eerste of tweede week van induksieterapie voor. Die seltelling normaliseer gewoonlik binne

2 tot5 dae na beëindiging van die middel ofverlaging van die dosis (sien afdeling 4.4).

Hulpstowwemet bekendeeﬀekte

VALHET ORAL SOLUTION poeier vir mondelingse oplossing bevat natriumbensoaat. Toename in bilirubien na die

verplasing van albumien kan neonatale geelsug verhoog, wat tot kernikterus kan ontwikkel (neerslag van

ongekonjugeerde bilirubien in die breinweefsel).

8 REGISTRASIENOMMER

54/20.2.8/0271

As umeer VALHETORALSOLUTIONgedrinkhetas watumoes

Raadpleeg u dokter of apteker in geval van oordosering. As nie een beskikbaar is nie, kontak die naaste hospitaal of

gifsentrum.

Te veel VALHETORALSOLUTIONkan ernstige newe-eﬀekte veroorsaak, veral metu bloed ofniere.

DATUMVAN EERSTEMAGTIGING

12 September 2023

Trombositopenie

4.5 Interaksies met ander medisyne enandervorms van interaksie

Die volgende medisyne, naamlik valasiklovir, didanosien, nelﬁnavir, siklosporien, omeprasool en mofetielmikofenolaat

het geen invloed op die permeabiliteit van valgansiklovir gehad nie (in vivo-rotmodel).

Pasiënte met 'n lae aantal bloedplaatjies by basislyn (< 100 100/μL) het 'n groter risiko om trombositopenie te ontwikkel.

Pasiënte met iatrogene immuunonderdrukking as gevolg van behandeling met immuunonderdrukkende middels, loop

'n groter risiko vir trombositopenie as pasiënte met VIGS (sien afdeling 4.4). Erge trombositopenie kan met potensiële

lewensbedreigende bloeding gepaard gaan.

10 DATUMVAN HERSIENINGVAN DIETEKS

VALHET ORAL SOLUTION word na gansiklovir gemetaboliseer. Daarom kan medisinale interaksies wat met

gansiklovir gepaardgaan, vir VALHETORALSOLUTIONverwag word.

As uvergeet omVALHETORALSOLUTIONte drink

As u u dosis met slegs 'n paar uur gemis het, drink die oorgeslane dosis sodra u onthou.As dit bykans tyd vir u volgende

dosis is, los die oorgeslane dosis en drink VALHETORALSOLUTIONop die volgende gewone geskeduleerde tyd.

23 Mei 2025

Aanmeld vanvermeende nadeligereaksies

Dit is belangrik om vermoedelike nadelige reaksies aan te meld na goedkeuring van die medisyne. Dit laat voortgesette

Interaksies met gansiklovir

Imipenem-silastatien