Valganciclovir

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:

• Cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS) patients
• Prevention of CMV disease in solid organ transplant patients who are at risk

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to ganciclovir
• Breastfeeding

Cautions

• Hypersensitivity to aciclovir or penciclovir (or to their prodrugs, valaciclovir or famciclovir respectively)
• Pregnancy
• Males of reproductive potential
• Renal impairment
• Hepatic impairment
• Elderly
• Haemodialysis
• Neutrophil count <500 cells/μl
• Platelet count <25000/μl
• Haemoglobin level <8g/dl
• Pre-existing haematological cytopenia
• History of drug-related haematological cytopenia
• Radiotherapy
• Prolonged induction treatment
• Lung and intestinal transplant
• May impair ability to drive and operate machinery

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

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: 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

South African Standard Treatment Guidelines indications and dosages

HIV cytomegalovirus (CMV) retinitis - limited

• Oral (tab, sol): Inital: 900mg, 12hrly; Treatment duration: 21 days; Maintenance: 900mg, dly; Treatment duration: Until CD4>100cells/mm³ and minimum of 3 months of therapy
  (STG, Adult 2019) 

Biopsy-proven CMV gastrointestinal disease and pneumonitis

• Oral (tab, sol): 900mg, 12hrly; Treatment duration: 3 weeks (specialist initiated)
  (STG, Adult 2023)

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Maintenance treatment is not indicated unless there has been a relapse

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Central nervous system CMV infection

• Oral (tab, sol): Initial: 900mg, 12hrly; Treatment duration: 3 weeks; Maintenance if good clinical response to initial treatment: 900mg, dly; Treatment duration: Until CD4>100cells/mm³ on antiretroviral therapy (specialist initiated)
  (STG, Adult 2023)

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Click here for the NDoH Utilisation Form

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Indications and dosages registered in other jurisdictions

Prevention of CMV disease in solid organ transplantation

• Oral (tab, sol): Initial: 900mg, dly; Treatment to start within 10 days of transplant; Treatment duration: Minimum 100 days post-transplantation (manufacturer recommendation)

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For kidney transplant patients, prophylaxis may be continued until 200 days post-transplantation

Paed. forms avail. in SA and covered in this monograph: tab, sol

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: 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

South African Standard Treatment Guidelines indications and dosages

Symptomatic congenital cytomegalovirus (CMV) infection

• Oral (tab, sol): 16mg/kg, 12hrly; Treatment duration: 6 months
  (STG, Paed. 2017)

Biopsy-proven CMV gastrointestinal disease in immunocompromised children 
- Following 7 days of IV ganciclovir
CMV pneumonia in immunocompromised children
- Following 7 days of IV ganciclovir

• Oral (tab, sol): 16mg/kg, 12hrly; Treatment duration: 5 weeks
  (STG, Paed. 2017)

CMV pneumonia in HIV exposed or infected children

• Oral (tab, sol): Initial: 16mg/kg, 12hrly; Treatment duration: 21 days; THEN 16mg/kg, dly; Treatment duration: 21 days (Total duration of treatment: 42 days)
  (STG, Paed. 2023)

Central nervous system CMV disease
- Following 7 days of IV ganciclovir

• Oral (tab, sol): Initial: 16mg/kg, 12hrly; Treatment duration: 5 weeks; Maintenance if good clinical response to initial treatment: 16mg/kg, dly, until CD4>100cells/mm³ on antiretroviral therapy (specialist initiated) 
  (STG, Paed. 2017) 

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Click here for NDoH Utilisation Form

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Indications and dosages registered in other jurisdictions

Prevention of CMV disease in solid organ transplantation

• Consult a specialist for dosages

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Should be administered with food

Pregnancy

• Caution; not recommended
• The safety of valganciclovir 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
• Valganciclovir should not be used in pregnancy unless the therapeutic benefit for the mother outweighs the potential risk of teratogenic damage to the foetus
• 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

Breastfeeding

• Contraindicated
• It is unknown if ganciclovir is excreted in human breast milk, but the possibility of ganciclovir being excreted in the breast milk and causing serious adverse reactions in the nursing infant cannot be discounted
• Animal data indicate that ganciclovir is excreted in the milk of lactating rats. Therefore, breastfeeding must be discontinued during treatment with valganciclovir

Fertility

• A small 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  
• 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
• Based on clinical and nonclinical studies, it is considered likely that ganciclovir (and valganciclovir) may cause temporary or permanent inhibition of human spermatogenesis

Renal Impairment

• CrCl ≥60 ml/min: Caution; no dose adjustment recommended 
• CrCl <60 ml/min: Caution; dose adjustment recommended 

CrCl (ml/min)	Induction dose	Maintenance/ Prevention dose
40 - 59	450mg 12hrly	450mg, 24hrly
25 - 39	450mg, 24hrly	225mg, 24hrly (sol) or 450mg, 48hrly (tab)
10 -24	225mg, 24hrly (sol) or 450mg, 48hrly (tab)	125mg, 24hrly (sol) or 450mg, twice weekly (tab)
<10 (Haemodialysis)	200mg, three times weekly after dialysis (sol) Use of the tablet is not recommended	100 mg, three times weekly after dialysis (sol) Use of the tablet is not recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no information available
  Since renal clearance decreases with age,  valganciclovir should be administered to elderly patients with special consideration of their renal status

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Insomnia
• Hypoaesthesia
• Paraesthesia
• Peripheral neuropathy
• Dizziness
• Convulsion
• Tremor
• Depression
• Anxiety
• Confusional state
• Psychotic disorder  
• Abnormal thinking
• Agitation
• Hallucinations
• Fatigue

Cardiovascular Disorders

• Arrhythmias
• Hypotension
• Chest pain

Respiratory Disorders

• Dyspnoea
• Cough
• Upper respiratory tract infection

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Dyspepsia
• Constipation
• Flatulence
• Dysphagia
• Abdominal distension
• Mouth ulceration
• Oral candidiasis
• Pancreatitis

Hepatobiliary Disorders

• Abnormal hepatic function
• Increased blood alkaline phosphatase
• Increased aspartate aminotransferase
• Increased alanine aminotransferase  

Genitourinary Disorders

• Renal failure
• Haematuria
• Urinary tract infection
• Male infertility

Endocrine and Metabolic Disorders

• Decreased appetite
• Decreased weight
• Anorexia

Musculoskeletal Disorders

• Back pain
• Myalgia
• Arthralgia
• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Dermatitis
• Night sweats
• Pruritus
• Rash
• Alopecia
• Urticaria
• Dry skin
• Cellulitis

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Anaemia
• Thrombocytopenia
• Agranulocytosis
• Granulocytopenia
• Leucopenia
• Pancytopenia
• Bone marrow failure
• Aplastic anaemia
• Hypersensitivity
• Anaphylactic reaction
• Sepsis
• Candida infections
• Pyrexia

Sensory Disorders

• Macular oedema
• Retinal detachment
• Vitreous floaters
• Eye pain
• Visual impairment
• Conjunctivitis
• Ear pain
• Deafness
• Dysgeusia

Others

• Influenza
• Chills

• Nucleoside analogues
• Didanosine
• Zidovudine
• Stavudine
• Nucleotide analogues
• Tenofiovir
• Adefovir
• Imipenem-cilastatin
• Probenecid
• Immunosuppressants
• Ciclosporin  
• Tacrolimus
• Mycophenolate mofetil
• Antineoplastic agents
• Doxorubicin
• Vinblastine
• Vincristine
• Hydroxyurea
• Anti-infective agents
• Trimethoprim/sulphonamides
• Dapsone
• Amphotericin B
• Flucytosine
• Pentamidine

• Full blood count

None routine. Specific cases may require

• Renal function
• Pregnancy test

Tablet 450mg - EML (Hospital)

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Equivalence to ganciclovir

• Valganciclovir is rapidly and extensively metabolised to ganciclovir after oral dosing. Oral valganciclovir 900 mg taken twice daily is therapeutically equivalent to IV ganciclovir 5 mg/kg taken twice daily.  
• The ganciclovir systemic exposure following administration of 900 mg valganciclovir oral solution is equivalent to valganciclovir 900 mg tablets

Precautions for handling

• Owing to the teratogenic character, the valganciclovir powder and reconstituted solution should be handled with caution. Inhalation should be avoided. Similarly, the tablets should not be broken or crushed. Contact with skin or mucous membranes should be avoided
• If broken or crushed tablets, 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 sterile water or plain water if sterile water is unavailable

Preparation of 50mg/ml powder for oral solution

• Measure 91ml of purified water in a graduated cylinder
• Add purified water to the bottle. Shake the closed bottle until the powder is dissolved forming a clear, colourless to brown solution
• Remove the child resistant cap and push the bottle adapter into the neck of the bottle
• Close bottle tightly with child resistant cap
• Write the date of expiration of the reconstituted solution on the bottle label

• It is recommended that valganciclovir powder for oral solution be reconstituted by a pharmacist prior to dispensing to the patient

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. The virustatic activity of ganciclovir is a result of the inhibition of viral DNA synthesis by competitive inhibition of the incorporation of deoxyguanosine triphosphate into DNA by DNA polymerase, and the incorporation of ganciclovir triphosphate into viral DNA, causing termination of viral DNA elongation.

Spectrum of activity: 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, HHV8), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) and hepatitis B virus (HBV)

Tablet 450mg

• Cytameg (Pharmacare Limited)
• Valcyte (Roche) originator
• Valhet 450mg ( Hetero Drugs South Africa)
• Valvir 450 (Cipla Medpro)

Solution (per ml) 50mg

• Valcyte (Roche) originator