Valaciclovir

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Herpes zoster (shingles)
• Episodic treatment of recurrent genital herpes in immunocompetent adult patients
• Prevention (suppression) of recurrent herpes simplex infection of the skin and mucous membrane of the ano-genital area
• Prophylaxis of cytomegalovirus (CMV) infection, CMV disease and other herpes virus infections following organ transplantation, where a special risk exists

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Mild to severe renal impairment (CrCl<75ml/min in cytomegalovirus infections)
• Moderate to severe renal impairment (CrCl<50ml/min in VZV and herpes labialis (HSV) infections)
• Severe renal impairment (CrCl<30ml/min in HSV infection)
• Moderate to severe renal impairment 
• Severe hepatic impairment
• Elderly 
• Dehydration or risk thereof 
• High doses 
• Complicated herpes zoster 
• Immunocompromised patients 
• Intercourse 
• Ocular herpes simplex virus infections
• Post transplant patients

Forms avail. in SA and covered in this monograph: tab

Infections caused by: Herpes simplex; Herpes zoster; Cytomegalovirus 

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Herpes zoster
- Immunocompetent patients 

• Oral (tab): 1000mg, 8hrly; Treatment duration: 7 days

- Immunocompromised patients 

• Oral (tab): 1000mg, 8hrly; Treatment duration: 7 days and continued for 2 days following crusting of lesions

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Patients should be advised to start treatment as soon as possible after a diagnosis of herpes zoster 

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In immunocompromised patients, antiviral treatment is suggested for patients presenting within one week of vesicle formation or at any time before full crusting of lesions

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Initial genital herpes
- Immunocompetent patients 

• Oral (tab): 500mg, 12hrly; Treatment duration: 3-10 days

- Immunocompromised patients

• Oral (tab): 1000mg, 12hrly; Treatment duration: 5-10 days

Recurrent genital herpes
- Immunocompetent patients 

• Oral (tab): 500mg, 12hrly; Treatment duration: 3-5 days

- Immunocompromised patients

• Oral (tab): 1000mg, 12hrly; Treatment duration: 5 days

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For recurrent episodes of herpes simplex treatment should commence ideally during the prodromal period or immediately upon appearance of the first signs or symptoms

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Herpes labialis

• Oral (tab): 2000mg, 12hrly; Treatment duration: 1 day

Suppression of recurrences of herpes simplex
- Immunocompetent patients with < 10 episodes per year 

• Oral (tab): 500mg, dly  

- Immunocompetent patients with > 10 episodes per year  

• Oral (tab): 250mg, 12hrly

- Immunocompromised patients 

• Oral (tab): 500mg, 12hrly

Prophylaxis of cytomegalovirus infection and disease

• Oral (tab): 2000mg; 6hrly; Treatment duration: 90 days

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Treatment to be initiated as early as possible post-transplant 

Not established for use in children below 12 years

Pregnancy

• Caution; no evidence of risk in studies
• A limited amount of data on the use of valaciclovir and a moderate amount of data on the use of aciclovir in pregnancy is available from pregnancy registries (which have documented the pregnancy outcomes in women exposed to valaciclovir or to oral or intravenous aciclovir (the active metabolite of valaciclovir); 111 and 1246 outcomes (29 and 756 exposed during the first trimester of pregnancy, respectively) and postmarketing experience indicate no malformative or foetal/neonatal toxicity. Animal studies do not show reproductive toxicity for valaciclovir. Valaciclovir should only be used in pregnancy if the potential benefits of treatment outweigh the potential risk

Breastfeeding

• Caution
• Aciclovir, the principle metabolite of valaciclovir, is excreted in breast milk. However, at therapeutic doses of valaciclovir, no effects on the breastfed newborns/ infants are anticipated since the dose ingested by the child is less than 2% of the therapeutic dose of intravenous aciclovir for treatment of neonatal herpes. Valaciclovir should be used with caution during breastfeeding and only when clinically indicated

Renal Impairment

Varicella-Zoster virus (VZV)/Herpes labialis (HSV) infections

• CrCl≥50ml/min: No dose adjustment recommended
• CrCl<50ml/min: Caution; dose adjustment recommended

Herpes Simplex virus (HSV) Infections

• CrCl≥30ml/min: No dose adjustment recommended
• CrCl<30ml/min: Caution; dose adjustment recommended

Cytomegalovirus (CMV) infections

• CrCl≥75ml/min: No dose adjustment recommended
• CrCl<75ml/min: Caution; dose adjustment recommended

Therapeutic Indication	Creatinine clearance (ml/min)	Dose
Varicella-zoster virus (VZV) infections
Treatment of herpes zoster (shingles) in immunocompetent and immunocompromised adults	≥50	No adjustment necessary
	30-49	1000mg, 12hrly
	10-29	1000mg, dly
	<10	500mg, dly
Herpes simplex virus (HSV) infections
Treatment of HSV infections
-immunocompetent adults and adolescents	≥30	No adjustment necessary
	<30	500mg, dly
- immunocompromised adults	≥30	No adjustment necessary
	<30	1000mg, dly
Treatment of herpes labialis (cold sores) in immunocompetent adults and adolescents  (alternative 1-day regimen)	≥50	No adjustment necessary
	30-49	1000mg, 12hrly, in one day
	10-29	500mg, 12hrly, in one day
	<10	500mg, as a single dose
Suppression of HSV infections
-immunocompetent adults and adolescents	≥30	No dose adjustment necessary
	<30	250mg, dly
- immunocompromised adults	≥30	No dose adjustment necessary
	<30	500mg, dly
Cytomegalovirus (CMV) infections
CMV prophylaxis in solid organ transplant recipients in adults and adolescents	≥75	No adjustment necessary
	50-<75	1500mg, 6hrly
	25-<50	1500mg, 8hrly
	10-<25	1500mg, 12hrly
	<10 or on dialysis	1500mg, dly

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended
  No data available on the use of higher doses of valaciclovir (4000 mg or more per day) in patients with liver disease
  Specific studies of valaciclovir have not been conducted in liver transplantation; Caution should be exercised when administering daily doses >4000mg to these patients

Elderly  

• Caution; no dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache 
• Dizziness
• Confusion 
• Hallucinations
• Decreased level of consciousness 
• Tremor 
• Agitation 
• Ataxia
• Dysarthria
• Seizures 
• Encephalopathy 
• Coma
• Delirium 
• Psychosis 

Respiratory Disorders

• Dyspnoea 

Gastrointestinal Disorders

• Vomiting 
• Diarrhoea
• Abdominal discomfort 

Hepatobiliary Disorders

• Increased hepatic function tests

Genitourinary Disorders

• Haematuria 
• Renal impairment 
• Renal pain 
• Acute renal failure 
• Intratubular precipitation of acyclovir crystals 

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis
• Photosensitivity 
• Urticaria 
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis 
• Leucopaenia 
• Thrombocytopaenia 
• Microangiopathic haemolytic anaemia

• Aminoglycosides
• Organoplatinum compounds
• Iodinated contrast media
• Methotrexate
• Pentamidine
• Foscarnet
• Ciclosporin
• Tacrolimus
• Cimetidine
• Probenecid 
• Aciclovir
• Tenofovir
• Mycophenolate motefil metabolite

• Renal function

Specific cases may require

• Hepatic function 
• Full blood count

Valaciclovir is phosphorylated by viral thymidine kinase to the active metabolite acyclovir triphosphate. This inhibits herpes viral DNA replication by competitive inhibition of viral DNA polymerase as well as by incorporation into and termination of the growing viral DNA chain. When used as a substrate for viral DNA polymerase, acyclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA by incorporating into the DNA strand and replacing many of the adenosine bases, resulting in the prevention of DNA synthesis.

Spectrum of activity: Herpes zoster virus; Herpes simplex virus; Cytomegalovirus 

Tablet 250mg

• Zelitrex (Litha Pharma) originator

Tablet 500mg

• Anviro (Zydus)
• Hevitrex (Bliss)
• Mylan Valaciclovir (Mylan)
• Shilova (Aurobindo)
• Valatrex  (Sandoz)
• Vavirex (Pharmacare) 
• Vorior (Hetero) 
• Zelitrex (Litha Pharm) originator
• Zelivire (Ranbaxy)

Tablet 1000mg

• Actiprez (Arrow)