Valganciclovir oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of valganciclovir.
Drugs List
Therapeutic Indications
Uses
Prevention of cytomegalovirus infection in solid organ transplant patients
Treatment of cytomegalovirus (CMV) retinitis in patients with AIDS
Induction and maintenance treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS).
Prevention of CMV disease in CMV-negative patients who have received a solid organ transplant from a CMV-positive donor.
Dosage
Adults
Strict adherence to dosage recommendation is essential to avoid overdose.
Induction treatment of CMV retinitis:
In patients with active CMV retinitis, the recommended dose is 900mg valganciclovir twice a day for 21 days.
Prolonged induction treatment may increase the risk of bone marrow toxicity.
Maintenance treatment of CMV retinitis:
Following induction treatment, or in patients with inactive CMV retinitis, the recommended dose is 900mg valganciclovir once daily.
Patients whose retinitis worsens may repeat induction treatment, however, consideration should be given to the possibility of viral drug resistance.
Prevention of CMV disease in solid organ transplantation
In transplant recipients the recommended dose is 900mg valganciclovir once a day. Treatment should start within ten days of transplantation and continue until 100 days post-transplantation.
For patients who have received a kidney transplant, prophylaxis may continue up to 200 days post-transplantation.
Children
Treatment of CMV retinitis
Contraindicated.
Prevention of CMV disease in solid organ transplantation
Children older than 16 years old
In transplant recipients the recommended dose is 900mg valganciclovir once a day. Treatment should start within ten days of transplantation and continue until 100 days post-transplantation.
For patients who have received a kidney transplant, prophylaxis may continue up to 200 days post-transplantation.
Birth to 16 years old
Paediatric dose (mg) = 7 x body surface area (BSA) metres square, derived from Mosteller BSA formula x creatinine clearance, derived from the Schwartz formula (CrCLS)
In transplant recipients the recommended once daily mg dose should start within ten days of transplantation and continue until 100 days post-transplantation.
For patients who have received a kidney transplant, prophylaxis may continue up to 200 days post-transplantation.
All calculated doses should be rounded to the nearest 25mg increment for the actual deliverable dose. If calculated dose exceeds 900mg, maximum dose of 900mg is to be administered. The oral solution formulation is preferred in order to administer the calculated doses however the solid oral formulation may be used if the calculated doses are within 10% of the available solid oral doses and the patient is able to swallow this formulation. For example, if the calculated dose is between 405mg and 495mg, one 450mg tablet may be taken.
Monitor serum creatinine levels regularly and consider changes in height and weight and adapt dose appropriately.
Mosteller formula
BSA metres square = square root of height (cm) x weight (kg) divided by 3600
Schwartz formula
Schwartz creatinine clearance (ml/minute/1.73 metres square) = k (based of Jaffe method of measuring serum creatinine) x height (cm) divided by serum creatinine (mg/dl)
where k = 0.45 for patients aged below 2 years, 0.55 for boys aged 2 to 12 and girls aged 2 to 16, and 0.7 for boys aged 13 to 16 years. Lowering of the k value may be necessary for appropriate sub-populations e.g. in paediatric patients with low birth weight.
Patients with Renal Impairment
Serum creatinine levels or creatinine clearance should be monitored carefully and dosage adjusted according to the creatinine clearance, as shown below:
Creatinine clearance 60 ml/minute or greater
No dosage adjustment necessary - see 'Dosage - Adults'
Creatinine clearance 40 to 59 ml/minute
Induction dose: 450mg twice daily
Maintenance/prevention dose: 450mg once daily
Creatinine clearance 25 to 39 ml/minute
Induction dose: 450mg once daily
Maintenance/prevention dose: 225mg once daily or 450mg (1 tablet) every other day
Creatinine clearance 10 to 24 ml/minute
Induction dose: 225mg once daily or 450mg (1 tablet) every other day
Maintenance/prevention dose: 125mg once daily or 450mg (1 tablet) twice weekly
Creatinine clearance less than 10ml/minute (using the oral solution only)
Induction dose: 200mg three times a week after dialysis
Maintenance/prevention dose: 100mg three times a week after dialysis
Additional Dosage Information
Valganciclovir is rapidly and extensively metabolised to ganciclovir after oral dosing. Oral valganciclovir 900mg twice daily is therapeutically equivalent to intravenous ganciclovir 5mg/kg twice daily.
Contraindications
Absolute neutrophil count below 0.5 x 10 to the power of 9 / L
Haemoglobin concentration below 8g / dL
Platelet count below 25 x 10 to the power of 9 / L
Breastfeeding
Pregnancy
Precautions and Warnings
Children under 18 years
Concurrent radiotherapy
Females of childbearing potential
History of cytopenic reaction
Cytopenia
Galactosaemia
Glucose-galactose malabsorption syndrome
Haemodialysis
Lactose intolerance
Renal impairment - creatinine clearance below 60ml/minute
Reduce dose in patients with creatinine clearance below 60ml/min
Advise ability to drive/operate machinery may be affected by side effects
May contain sodium benzoate: may increase risk of jaundice in neonates
Some formulations contain lactose
Avoid contact of powder with skin and mucous membranes
Avoid contact of prepared solution with skin and mucous membranes
Monitor full blood count regularly
Monitor height and weight in children
Monitor serum creatinine
Consider treatment with blood growth factors if severe cytopenias develop
Consider dose interruption if patient develops severe cytopenias
Adjust dose if switching patient from ganciclovir (not bioequivalent)
Not licensed for all indications in all age groups
May cause impaired fertility
Female: Contraception required during and for 1 month after treatment
Male: Use barrier contraception during and for 3 months after treatment
In animal studies, ganciclovir was found to be mutagenic, teratogenic, aspermatogenic and carcinogenic, and a suppressor of female fertility. Valganciclovir should be considered a potential teratogen and carcinogen in humans with the potential to cause birth defects and cancers. It is also considered likely that valganciclovir causes temporary or permanent inhibition of spermatogenesis. Before valganciclovir treatment is commenced patients should be advised of the potential risks to the foetus.
If prophylaxis is extended beyond 100 days the possible risk of developing leucopenia and neutropenia should be taken into consideration.
It is recommended that complete blood counts and platelet counts be monitored during therapy. Increased haematological monitoring may be warranted in patients with renal impairment. In patients developing severe leucopenia, neutropenia, anaemia, thrombocytopenia and/or pancytopenia it is recommended that treatment with haematopoietic growth factors and/or dose interruption be considered.
The bioavailability of ganciclovir after a single dose of 900mg valganciclovir is approximately 60%, compared with approximately 6% after administration of 1000mg oral ganciclovir (as capsules). Excessive exposure to ganciclovir may be associated with life-threatening adverse reactions. Dose recommendations should be closely followed when instituting therapy, when switching from induction to maintenance treatment, and in patients who may switch from oral ganciclovir to valganciclovir as valganciclovir cannot be substituted for ganciclovir capsules on a milligram-to-milligram basis.
Lung and intestinal transplant patients were not included in the clinical study using valganciclovir for the prevention of CMV disease in transplantation so experience in these patients is limited.
Pregnancy and Lactation
Pregnancy
Valganciclovir is contraindicated during pregnancy.
The manufacturer does not recommend using valganciclovir during pregnancy. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Valganciclovir is contraindicated during breastfeeding.
Use of valganciclovir when breastfeeding is contraindicated by the manufacturer. It is unknown if valganciclovir is excreted in breast milk, however the possibility of it causing serious adverse reactions in the nursing infant cannot be discounted. Therefore, breastfeeding must be discontinued.
Side Effects
Abdominal distension
Abdominal pain
Abnormal thinking
Agitation
Agranulocytosis
Allogeneic transplant rejection
Alopecia
Anaemia
Anaphylactic reaction
Anorexia
Anxiety
Aplastic anaemia
Arrhythmias
Arthralgia
Asthenia
Back pain
Bacteraemia
Bone marrow depression
Candidiasis (mouth or throat)
Cellulitis
Chest pain
Chills
Confusion
Conjunctivitis
Constipation
Convulsions
Cough
Deafness
Decrease in creatinine clearance
Decreased appetite
Depression
Dermatitis
Diarrhoea
Dizziness
Dry skin
Dysgeusia
Dyspepsia
Dysphagia
Dyspnoea
Ear pain
Eye pain
Fatigue
Flatulence
Granulocytopenia
Haematuria
Hallucinations
Headache
Hepatic impairment
Hypersensitivity reactions
Hypoaesthesia
Hypotension
Increase in alkaline phosphatase
Increase in serum ALT/AST
Infections
Infertility
Influenza
Insomnia
Jaundice
Leucopenia
Macular oedema
Malaise
Mouth ulcers
Muscle spasm
Myalgia
Nausea
Neutropenia
Night sweats
Pain
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Pruritus
Psychotic disorder
Pyrexia
Rash
Renal failure
Renal impairment
Retinal detachment
Seizures
Sepsis
Serum creatinine increased
Thrombocytopenia
Tremor
Urticaria
Visual disturbances
Vitreous disorder
Vomiting
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T. and Rowe, H, Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Valcyte 450 mg film-coated tablets. Roche Products Limited. Revised May 2018.
Summary of Product Characteristics: Valcyte 50 mg/ml powder for oral solution. Roche Products Limited. Revised December 2020.
Summary of Product Characteristics: Valganciclovir 450 mg film-coated tablets. TEVA UK Limited. Revised April 2016.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 November 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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