- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of valaciclovir.
Drugs List
Therapeutic Indications
Uses
Treatment of herpes zoster (shingles) in immunocompetent adults and in mild or moderate immunosuppressed adults.
Treatment of ophthalmic zoster in immunocompetent adults.
Treatment of herpes simplex infections of the skin and mucous membranes (including initial and recurrent genital herpes) in immunocompetent adults and adolescents, and in immunocompromised adults.
Suppression of herpes simplex infections of the skin and mucous membranes (including recurrent genital herpes) in immunocompetent adults and adolescents, and in immunocompromised adults.
Treatment of ocular herpes simplex infections.
Suppression of recurrent ocular herpes simplex infections.
Prophylaxis of cytomegalovirus (CMV) infection and disease following solid organ transplantation in adults and adolescents.
Dosage
Treatment should commence as soon as possible.
Adults
Herpes simplex
Immunocompetent patients
500mg twice a day, for a duration of 3 to 5 days. If considered necessary, the duration of treatment may be extended to 10 days for initial or severe infections.
For suppression of recurrent herpes simplex, 500mg once a day. Dose may also be given in two divided doses in frequent recurrences. After 6 to 12 months, treatment should be re-evaluated.
Immunocompromised patients
1g twice a day, for at least 5 days. If considered necessary, the duration of treatment may be extended to 10 days for initial or severe infections.
For suppression of recurrent herpes simplex, 500mg twice a day. After 6 to 12 months, treatment should be re-evaluated.
Treatment of herpes labialis
2g twice a day, for 1 day. The second dose must be administered at least 6 hours after the first dose, but no longer than 12 hours.
Treatment should not continue for longer than 1 day.
Prophylaxis of CMV infection and disease after solid organ transplantation
2g four times a day, for a period of 90 days.
Duration of treatment may be extended if considered necessary.
Herpes zoster and ophthalmic zoster
Immunocompetent patients
1g to be taken 3 times a day for 7 days.
Immunocompromised patients
1g to be taken 3 times a day for at least 7 days. Treatment should be continued for a further 2 days, following crusting of lesions.
It is recommended to administer antiviral treatment within 1 week of vesicle formation, before full crusting of lesions.
Children
Children aged 12 to 18 years
Herpes simplex
Immunocompetent patients
500mg twice a day, for a duration of 5 days. If considered necessary, the duration of treatment may be extended to 10 days for initial or severe infections.
For suppression of recurrent herpes simplex, 500mg twice a day, for a duration of 3 to 5 days.
Immunocompromised patients
1g twice a day, for a duration on 10 days for initial or severe infections.
For suppression of recurrent herpes simplex, 1g twice a day, for a duration of 5 to 10 days.
Treatment of herpes labialis
2g twice a day, for 1 day. The second dose must be administered at least 6 hours after the first dose, but no longer than 12 hours.
Treatment should not continue for longer than 1 day.
Prophylaxis of CMV infection and disease after solid organ transplantation
2g four times a day, for a period of 90 days.
Duration of treatment may be extended if considered necessary.
Treatment of herpes zoster in immunocompromised patients (unlicensed)
1g to be taken three times a day for at least 7 days. Treatment should be continued for a further 2 days, following crusting of lesions.
Children under 12 years
Contraindicated.
Patients with Renal Impairment
Caution and dose adjustment is required in patients with renal impairment. Adequate hydration should be maintained. The creatinine clearance should be monitored frequently and valaciclovir dosage adjusted accordingly, particularly during periods when renal function is changing rapidly e.g. immediately after renal transplantation or engraftment. Patients receiving intermittent haemodialysis should receive the dose after haemodialysis on dialysis days.
Treatment of herpes zoster
Immunocompetent and immunocompromised adults
Creatinine clearance 50ml/minute and above: 1g three times a day.
Creatinine clearance 30ml/minute to 50ml/minute: 1g twice a day.
Creatinine clearance 10ml/minute to 30ml/minute: 1g once a day.
Creatinine clearance less than 10ml/minute: 500mg once a day.
Treatment of herpes simplex
Immunocompetent adults and adolescents
Creatinine clearance 30ml/minute and above: 500mg twice a day.
Creatinine clearance less than 30ml/minute: 500mg once a day.
Immunocompromised adults
Creatinine clearance 30ml/minute and above: 1g twice a day.
Creatinine clearance less than 30ml/minute: 1g once a day.
Treatment of herpes labialis
Immunocompetent adults and adolescents
Creatinine clearance 50ml/minute and above: 2g twice a day, for 1 day.
Creatinine clearance 30ml/minute to 50ml/minute: 1g twice a day, for 1 day.
Creatinine clearance 10ml/minute to 30ml/minute: 500mg twice a day, for 1 day.
Creatinine clearance less than 10ml/minute: 500mg once only.
Suppression of recurrent herpes simplex
Immunocompetent adults and adolescents
Creatinine clearance 30ml/minute and above: 500mg once a day.
Creatinine clearance less than 30ml/minute: 250mg once a day.
Patients with very frequent recurrences (10 or more a year) may see benefit from taking a divided dose of 250mg twice a day.
Immunocompromised adults
Creatinine clearance 30ml/minute and above: 500mg twice a day.
Creatinine clearance less than 30ml/minute: 500mg once a day.
Prophylaxis of CMV infection and disease after solid organ transplantation in adults and adolescents
Creatinine clearance 75ml/minute and above: 2g four times a day.
Creatinine clearance 50ml/minute to less than 75ml/minute: 1.5g four times a day.
Creatinine clearance 25ml/minute to less than 50ml/minute: 1.5g three times a day.
Creatinine clearance 10ml/minute to less than 25ml/minute: 1.5g twice a day.
Creatinine clearance less than 10ml/minute or on dialysis: 1.5g once a day.
Patients with Hepatic Impairment
Mild to moderate cirrhosis
Studies with 1g dose have shown that dose adjustment is not required in these patients (hepatic synthetic function maintained).
Severe cirrhosis
Pharmacokinetic data does not indicate a need for dose adjustment (impaired hepatic synthetic function and evidence of portal-systemic shunting), however clinical experience is limited.
There are no data available for the use of 4g and higher doses of valaciclovir in hepatically impaired patients or those with liver transplant. Therefore, caution should be exercised when administering doses greater than 4g to these patients.
Administration
For oral administration.
Contraindications
Children under 12 years of age.
Precautions and Warnings
Patients that are at risk of dehydration, such as the elderly and patients with renal impairment, should maintain adequate hydration.
Valaciclovir is eliminated by renal clearance therefore the dose of valaciclovir must be reduced in patients with renal impairment. See Dosage - Renal Impairment .
Elderly patients are more likely to have a reduced renal function and therefore the need for dose reduction should be considered. Both the elderly and renally impaired patients are at higher risk of developing neurological side effects and should be closely monitored for any evidence of these effects. These reactions are normally reversible after discontinuation of valaciclovir.
The clinical response should be closely monitored in immunocompromised patients with herpes zoster. Intravenous antiviral therapy should be considered when response to oral therapy is inadequate. Patients that have visceral involvement, disseminated zoster, motor neuropathies, encephalitis and cerebrovascular complications should be treated with intravenous antiviral therapy. Immunocompromised patients with ophthalmic zoster or those with a high risk for disease dissemination and visceral organ involvement should also be treated with intravenous antiviral therapy.
It is advised to abstain from intercourse when symptoms of genital herpes are present even when antiviral therapy has been initiated. The frequency of viral shedding is significantly reduced during suppressive treatment with antiviral agents, however, the risk of transmission is still possible. It is advised that in addition to valaciclovir therapy adequate safe sex practices are adhered to.
The clinical response should be closely monitored closely in patients with ocular herpes simplex . Intravenous antiviral therapy should be considered when response to the oral therapy is unlikely to be adequate.
Valaciclovir should only be used in transplant patients who are at high risk of CMV disease (donor CMV-positive/recipient CMV-negative or use of anti-thymocyte globulin induction therapy) when safety concerns prohibit the use of valganciclovir or ganciclovir.
There may be a higher incidence of adverse effects (including CNS abnormalities) in patients who are administered high doses of valaciclovir for CMV prophylaxis compared to lower doses for other indications. Renal function should be closely monitored in this group of patients and dose adjusted accordingly.
Hepatic impairment - see Dosage; Hepatic Impairment.
Pregnancy - see 'Pregnancy' section.
Breastfeeding - see 'Lactation' section.
Pregnancy and Lactation
Pregnancy
Valaciclovir should only be used during pregnancy when the benefits outweigh the risk.
Valaciclovir has not shown evidence of teratogenicity during animal studies. Limited data is available on the use of valaciclovir during human pregnancy. More experience lies with the active metabolite aciclovir, for which no adverse effects on the foetus or newborn have been reported. Aciclovir readily crosses the human placenta and is largely present in the amniotic fluid but not in the foetus. Oral treatment of primary genital herpes-simplex infections is indicated for the use of aciclovir in order to prevent adverse foetal outcomes. Due to the low risk factor associated with aciclovir it is often considered the first choice for its' indications. Treatment with valaciclovir is recommended by Briggs for the treatment of first episode, recurrent episodes and daily suppression (from 36 weeks' gestation until delivery) of herpes-simplex infections. However, only aciclovir is indicated for severe infections.
Based upon combined data, the use of valaciclovir during pregnancy is considered low risk. Long-term follow up of children exposed to valaciclovir during foetal development is recommended. Schaefer advises that accidental exposure to valaciclovir during pregnancy does not require invasive diagnosis or termination of pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Aciclovir, the active metabolite of valaciclovir, is secreted in breast milk. However, the dosage of aciclovir in breast milk is less than 1% of the typical infant dose and therefore considered not clinically relevant. No adverse effects on the infant have been reported during breastfeeding when taking aciclovir. The manufacturer advises caution when administering valaciclovir to breastfeeding mothers.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Effects on Ability to Drive and Operate Machinery
No studies are available on the effects of valaciclovir on driving or operating machinery. However, ability to drive or operate machinery may be affected by side effects such as dizziness.
Counselling
Patients at risk of dehydration should be advised to maintain adequate hydration, especially the elderly and patients with renal impairment.
When used to treat or prevent genital herpes, patients should be advised to use safe sex practices (particularly the use of condoms) in addition to therapy with valaciclovir.
Advise patient that side effects such as dizziness may affect the ability to drive or operate machinery.
Side Effects
Headache
Nausea
Thrombotic thrombocytopenic purpura
Haemolytic uraemic syndrome
Acute renal failure
Leucopenia
Thrombocytopenia
Anaphylaxis
Dizziness
Confusion
Hallucinations
Altered consciousness
Tremor
Agitation
Ataxia
Dysarthria
Convulsions
Encephalopathy
Coma
Psychotic symptoms
Neurological disorders
Dyspnoea
Vomiting
Diarrhoea
Abdominal discomfort
Disturbances in liver enzymes and bilirubin (transient)
Rash
Photosensitivity
Pruritus
Urticaria
Angioedema
Renal pain
Crystal deposition in the kidney
Renal failure
Renal impairment
Microangiopathic haemolytic anaemia syndrome
Fatigue
Hepatitis
Jaundice
Anaemia
Delirium
Haematuria
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 ).
Shelf Life and Storage
Store below 30 degrees C
Further Information
Last Full Review Date: October 2011
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Valtrex Tablets 250mg. GlaxoSmithKline UK. Revised April 2014.
Summary of Product Characteristics: Valtrex Tablets 500mg. GlaxoSmithKline UK. Revised April 2014.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Valacyclovir. Last revised: February 3, 2009
Last accessed: October 19, 2011
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 August 2017
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.