Famciclovir

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) infection
• First episode herpes genitalis and recurrent genital herpes infections
• Suppression of recurrent genital herpes in immunocompromised patients

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to penciclovir

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Severe hepatic impairment
• Immunocompromised patients (see additional prescribing points)
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

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

Infections caused by: Varicella-zoster virus, Herpes simplex virus, Epstein-Barr virus, 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 manufacturer's recommendations:

Herpes zoster (shingles) infection

• Oral (tab): 250mg, 8hrly; Initiate within 72 hours of after rash onset; Treatment duration: 7 days

Genital herpes infection
- First episode

• Oral (tab): 250mg, 8hrly; Initiate within 72 hours of appearance of symptoms; Treatment duration: 5 days

- Recurrent genital herpes infections

• Oral (tab): 125mg, 12hrly; Initiate within 6 hours of appearance of symptoms; Treatment duration: 5 days

Suppression of recurrent genital herpes in immunocompetent patients

• Oral (tab): 125-250mg, 12hrly

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The length of treatment depends upon the severity of the disease. Therapy should be re-evaluated after 12 months in order to observe possible changes in the natural history of the disease

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International manufacturer's recommendations:

Herpes zoster and ophthalmic zoster in immunocompetent patients

• Oral (tab): 500mg, 8hrly; Treatment duration: 7 days

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Treatment should be initiated as soon as possible after a diagnosis of herpes zoster or ophthalmic zoster

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Herpes zoster in immunocompromised patients

• Oral (tab): 500mg, 8hrly; Treatment duration 10 days

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Treatment should be initiated as soon as possible after diagnosis  

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Genital herpes in immunocompetent patients
- First episode

• Oral (tab): 250mg, 8hrly; Treatment duration: 5 days

- Episodic treatment of recurrent herpes

• Oral (tab): 125mg, 12hrly; Treatment duration: 5 days

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First episode: Initiation of treatment is recommended as soon as possible after a diagnosis of first episode of genital herpes

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Episodic treatment of recurrent herpes: Initiation of treatment is recommended as soon as possible after onset of prodromal symptoms (e.g. tingling, itching, burning, pain) or lesions

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Recurrent genital herpes in immunocompromised patients

• Oral (tab): 500mg, 12hrly; Treatment duration: 7 days

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Initiation of treatment is recommended as soon as possible after onset of prodromal symptoms (e.g. tingling, itching, burning, pain) or lesions

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Suppression of recurrent genital herpes in immunocompetent patients

• Oral (tab): 250mg, 12hrly; Max duration: 12 months

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Suppressive therapy should be discontinued after a maximum of 12 months of continuous antiviral therapy to reassess recurrence frequency and severity

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The minimum period of reassessment should include two recurrences. Patients who continue to have significant disease may restart suppressive therapy

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Suppression of recurrent genital herpes in immunocompromised patients

• Oral (tab): 500mg, 12hrly

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Patients should be advised to avoid intercourse when symptoms are present even if treatment with an antiviral has been initiated. During suppressive treatment with antiviral agents, the frequency of viral shedding is significantly reduced. However, transmission is still possible. Therefore, in addition to therapy with famciclovir, it is recommended that patients use safer sex practices

Not established for use in children below 18 years

Pregnancy

• Caution
• There is a limited amount of data (less than 300 pregnancy outcomes) from the use of famciclovir in pregnant women. Based on these limited amounts of information, the cumulative analysis of both prospective and retrospective pregnancy cases did not provide evidence indicating that the product causes any specific foetal defect or congenital anomaly
• Animal studies have not shown any embryotoxic or teratogenic effects with famciclovir or penciclovir (the active metabolite of famciclovir)
• Famciclovir should only be used during pregnancy when the potential benefits of treatment outweigh the potential risks
• There are no data supporting any special recommendations in women of childbearing potential

Breastfeeding

• Caution
• It is unknown whether famciclovir is excreted in human breast milk. Animal studies have shown excretion of penciclovir in breast milk
• If the woman's condition mandates treatment with famciclovir, discontinuation of breastfeeding may be considered

Fertility

• Clinical data do not indicate an impact of famciclovir on male fertility following long-term treatment at an oral dose of 250mg twice daily

Renal Impairment

• Caution; dose adjustment recommended

Indication and nominal dose regimen	Creatinine clearance (ml/min)	Adjusted dose regimen
Herpes zoster in immunocompetent adults
500mg, 8hrly; Treatment duration: 7 days	≥60	500mg, 8hrly for 7 days
	40-59	500mg, 12hrly for 7 days
	20-39	500mg, dly for 7 days
	<20	250mg, dly for 7 days
	Haemodialysis	250mg following each dialysis during 7 days
Herpes zoster in immunocompromised adults
500mg, 8hrly; Treatment duration: 10 days	≥60	500mg, 8hrly for 10 days
	40-59	500mg, 12hrly for 10 days
	20-39	500mg, dly for 10 days
	<20	250mg, dly for 10 days
	Haemodialysis	250mg following each dialysis during 10 days
Genital herpes in immunocompetent adults - first episode of genital herpes
250mg, 8hrly; Treatment duration: 5 days	≥40	250mg, 8hrly for 5 days
	20-39	250mg, 12hrly for 5 days
	<20	250mg, dly for 5 days
	Haemodialysis	250mg following each dialysis during 5 days
Genital herpes in immunocompetent adults - episodic treatment of recurrent genital herpes
125mg, 12hrly; Treatment duration: 5 days	≥20	125mg, 12hrly for 5 days
	<20	125mg, dly for 5 days
	Haemodialysis	125mg following each dialysis during 5 days
Genital herpes in immunocompromised adults – episodic treatment of recurrent genital herpes
500mg, 12hrly; Treatment duration: 7 days	≥40	500mg, 12hrly for 7 days
	20-39	500mg, dly for 7 days
	<20	250mg, dly for 7 days
	Haemodialysis	250mg following each dialysis during 7 days
Suppression of recurrent genital herpes in immunocompetent adults
250mg, 12hrly	≥40	250mg, 12hrly
	20-39	125mg, 12hrly
	<20	125mg, dly
	Haemodialysis	125mg following each dialysis
Suppression of recurrent genital herpes in immunocompromised adults
500mg, 12hrly	≥40	500mg, 12hrly
	20-39	500mg, dly
	<20	250mg, dly
	Haemodialysis	250mg following each dialysis

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  Famciclovir has not been studied in patients with severe hepatic impairment. Conversion of famciclovir to its active metabolite penciclovir may be impaired in these patients resulting in lower penciclovir plasma concentrations, and thus a decrease of efficacy of famciclovir may occur

Elderly

• No dose adjustment recommended
  Dose modification is not required unless renal function is impaired

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Somnolence (predominantly in the elderly)
• Confusion (predominantly in the elderly)
• Hallucinations
• Seizure

Cardiovascular Disorders

• Palpitations

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Diarrhoea

Hepatobiliary Disorders

• Abnormal hepatic function tests
• Cholestatic jaundice

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Urticaria
• Serious skin reactions
  - Stevens-Johnson Syndrome
  - Toxic epidermal necrolysis
  - Erythema multiforme
• Hypersensitivity vasculitis
• Angioedema
  - Face oedema
  - Eyelid oedema
  - Periorbital oedema
  - Pharyngeal oedema

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Anaphylactic shock
• Anaphylactic reaction

• Probenecid
• Raloxifen 

None routine. Specific cases may require

• Full blood count
• Renal function

Immunocompromised patients with herpes zoster

• Clinical response should be closely monitored. Consideration should be given to intravenous antiviral therapy when response to oral therapy is considered insufficient
• Patients with complicated herpes zoster i.e. those with visceral involvement, disseminated zoster, motor neuropathies, encephalitis and cerebrovascular complications should be treated with intravenous antiviral therapy
• Moreover, immunocompromised patients with ophthalmic zoster or those with a high risk for disease dissemination and visceral organ involvement should be treated with intravenous antiviral therapy

Famciclovir is the oral prodrug of penciclovir. Famciclovir is rapidly converted in vivo into penciclovir. In virus-infected cells the viral thymidine kinase (TK) phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. This triphosphate inhibits viral DNA chain elongation by competitive inhibition with deoxyguanosine triphosphate for incorporation into the growing viral DNA, thus halting virus replication of viral DNA.

Spectrum of activity: Herpes simplex viruses (HSV types 1 and 2), Varicella zoster virus, Epstein-Barr virus, Cytomegalovirus

Tablet 125mg

• Ciplaflam (Cipla)
• Famvir (Novartis) originator
• Macleods Famciclovir (Macleods Pharmaceuticals)

Tablet 250mg

• Ciplaflam (Cipla)
• Famvir (Novartis) originator
• Macleods Famciclovir (Macleods Pharmaceuticals)