Consumer medicine information

Favic Treatment of cold sores

CMI for patients with cold sores

Famciclovir

BRAND INFORMATION

Brand name

Favic

Active ingredient

Famciclovir

Schedule

SUMMARY CMI

FAVIC

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using FAVIC?

FAVIC contains the active ingredient famciclovir. It is an antiviral medicine that is used to treat recurrent outbreaks of cold sores in adults who have a normal immune system.

For more information, see Section 1. Why am I using FAVIC? in the full CMI.

2. What should I know before I use FAVIC?

Do not use if you have ever had an allergic reaction to FAVIC or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use FAVIC? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with FAVIC and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use FAVIC?

Your doctor will give you instruction on how to take FAVIC tablets.

More instructions can be found in Section 4. How do I use FAVIC? in the full CMI.

5. What should I know while using FAVIC?

Things you should do	Tell your doctor if you become pregnant, make sure you tell your doctor or pharmacist before taking any further doses of FAVIC. Tell your doctor if you are about to be started on any new medicine. Tell any other doctor or dentist you visit that you or your child are using FAVIC.
Things you should not do	Do not take less than the recommended dose of 3 tablets, unless advised by your pharmacist. Do not use FAVIC to treat any other medical complaints unless your doctor tells you to. Do not give FAVIC to anyone else, even if they have the same condition as you.
Driving or using machines	Be careful driving or operating machinery until you know how FAVIC affects you. This medicine can cause dizziness, sleepiness or confusion in some people.
Drinking alcohol	Avoid drinking alcohol
Looking after your medicine	Store FAVIC tablets in original carton at below 25°C until ready for use.

For more information, see Section 5. What should I know while using FAVIC? in the full CMI.

6. Are there any side effects?

Side effects of this medicine may include headache; dizziness; abdominal pain or bloating; nausea; vomiting; diarrhoea; itching or an itchy rash (urticaria); abnormal liver function test results; extreme sleepiness; hallucinations; painful or swollen joints; aching muscles; yellowing of the skin or eyes; palpitations; a rash on other parts of your body; swelling below the surface of the skin; severe blistering of the skin; unexplained bruising; purple patches, itching, burning of the skin; seizures or fits; difficulty breathing or swallowing, wheezing or coughing.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

FAVIC Treatment of Cold Sores

Active ingredient(s): famciclovir

Consumer Medicine Information (CMI)

This leaflet provides important information about using FAVIC. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using FAVIC.

Where to find information in this leaflet:

1. Why am I using FAVIC?
2. What should I know before I use FAVIC?
3. What if I am taking other medicines?
4. How do I use FAVIC?
5. What should I know while using FAVIC?
6. Are there any side effects?
7. Product details

1. Why am I using FAVIC?

FAVIC is an antiviral medicine that is used to treat recurrent outbreaks of cold sores in adults who have a normal immune system.

Cold sores are an infection caused by a virus called herpes simplex type 1 (HSV-1). The infection is most commonly acquired as a baby or child from contact with parents or relatives, often from kissing.

Cold sores usually begin on or around the lips, mouth, and nose as small red bumps that turn into fluid-filled blisters. Cold sores can be tender and painful. Many people who get cold sores know when one is coming by a tingling, burning, itchy or painful sensation or redness in the area. This can happen very rapidly.

After redness and swelling develop, blisters form. The blisters may weep or burst and this can be painful. Then a shallow ulcer and yellow crust form as the cold sore dries. The crust eventually falls off, exposing new pink-coloured skin. Generally, the sores heal without scarring. After the initial infection has healed, the virus becomes dormant in nerve cells.

Cold sores can be unpredictable. The virus can become active again in the body, even after many years, resulting in recurrent outbreaks.

Even after many years, some people may experience recurring cold sores due to viral reactivation.

Some common triggers to a cold sore may include:

sun exposure
stress
fatigue
menstrual periods
fever
illness
dry chapped lips
skin trauma
a cold.

FAVIC does not cure the viral infection, however it helps to relieve the symptoms and shorten the duration of an outbreak.

The best results are obtained if the medicine is started as soon as possible after the first symptoms are noticed. These include tingling, itching or burning, or the appearance of redness or swelling. This is when the virus is reproducing rapidly.

2. What should I know before I use FAVIC?

Warnings

Do not use FAVIC if you are allergic medical conditions:

Famciclovir, the active ingredient
Penciclovir, a related antiviral medicine
Any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include shortness of breath, Skin rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, wheezing or troubled breathing.

Do not use FAVIC if:

the packaging is torn or shows signs of tampering
the expiry date printed on the pack has passed.

Tell your doctor or pharmacist if you are allergic to any other medicines, foods, preservatives, or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

problems with your immune system (which helps fight off infections)
kidney disease
liver disease.

Your doctor may want to take special care if you have any of these conditions.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

FAVIC should not be used during pregnancy unless necessary. Your doctor will discuss with you the potential risks of taking FAVIC during pregnancy, and will also advise you if you should take FAVIC while breast-feeding, based on the benefits and risks of your personal situation.

Talk to your doctor or pharmacist if you are not sure whether you should start taking this medicine.

If you have not told them about any of the above, tell him/her before you start taking FAVIC.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking FAVIC against the benefits they expect it will have for you.

There is no evidence that FAVIC is addictive.

FAVIC is not recommended for use in children or adolescents under 18 years of age.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and FAVIC may interfere with each other. These include:

probenecid, a prescription medicine used to treat gout (a disease with painful, swollen joints caused by uric acid crystals) and to increase blood levels of penicillin-type antibiotics
raloxifene, a medicine used to treat osteoporosis (a disease which causes bones to become less dense, gradually making them weaker, more brittle and likely to break)
medicines that can affect your kidneys.

You may need to take different amounts of these medicines or you may need to take different medicines. Your doctor and pharmacist have more information.

Your doctor OR Pharmacist can tell you what to do if you are taking any of these medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

4. How do I use FAVIC?

The usual dose is three 500 mg tablets taken together as a single dose. Swallow the tablets whole with a full glass of water.

The tablets may be taken with or without food. It is not necessary to chew or crush the tablet.

Follow all directions given to you by your doctor or pharmacist carefully.

These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask the doctor or pharmacist for help.

When to take FAVIC

Take FAVIC tablets as soon as possible after the first symptoms of a cold sore appear.

Symptoms include tingling, itching or burning or the appearance of redness and swelling.

Do not take the tablets if a hard crust has already formed on the cold sore.

Keep the tablets for the next episode.

How long to take it for

A single dose of FAVIC is all that is necessary for treating each episode of cold sores. The dose may be repeated if cold sores recur. Each pack of FAVIC for cold sores contains enough medicine for one dose.

If you use too much (Overdose)

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26) for advice, or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need medical attention.

5. What should I know while using FAVIC?

Things you should do

If you become pregnant, make sure you tell your doctor or pharmacist before taking any further doses of FAVIC.

They can discuss with you the risks of taking it while you are pregnant.

Remind your doctor and pharmacist that you are taking FAVIC if you are about to be started on any new medicine.

Tell any other doctors, dentists and pharmacists who are treating you that you are taking FAVIC.

Things you should not do

Do not take less than the recommended dose of 3 tablets, unless advised by your pharmacist.

If you stop your tablets suddenly, your condition may worsen or you may have unwanted side effects.

Do not take FAVIC to treat any other conditions unless your doctor or pharmacist tells you to.

Do not give FAVIC to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful driving or operating machinery until you know how FAVIC affects you.

This medicine can cause dizziness, sleepiness or confusion in some people.

Things that may help your condition

Cold sores are contagious and the virus can be passed on from person to person through close physical contact or saliva, even when blisters are not present. The risk is much higher when the cold sore is visible, as the virus can be shed, making it easy to infect other people.

Take the following precautions to avoid spreading the virus:

keep the areas affected by the virus as clean and dry as possible
avoid touching or scratching the sore area as you may spread the virus on your fingers
do not share any objects that have been in contact with a cold sore (e.g. drinking glasses, eating utensils, or towels)
avoid direct skin-to-skin contact of the area with other people (e.g. kissing) until the cold sore has healed.

Looking after your medicine

Keep your tablets in the blister pack, until it is time to take them.

If you take the medicine out of the pack it may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store FAVIC or any other medicines in a bathroom or near a sink.

Do not leave it in the car or on windowsills.

Heat and dampness can destroy some medicines.

Keep FAVIC where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

When to discard your medicine

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

6. Are there any side effects?

Tell the doctor or pharmacist as soon as possible if you or your child do not feel well while you are taking FAVIC.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Less serious side effects

Less Serious Side effects	What to do
headache dizziness nausea (feeling sick) or vomiting diarrhoea itching or an itchy rash (urticaria) abnormal liver function test results.	Speak to your doctor or Pharmacist if you have any of these less side effects and they worry you.

These side effects are usually mild.

Serious side effects

Serious side effects	What to do
a rash on other parts of your body extreme sleepiness or confusion, usually in older people hallucinations (seeing or hearing things that are not really there) painful or swollen joints aching muscles or muscle tenderness or weakness that is not caused by exercise. yellowing of the skin or eyes (signs of jaundice) palpitations (signs of abnormal heart beat)	Speak to your doctor or Pharmacist as soon as possible if you have any of these side effects.
swelling below the surface of the skin (e.g. swelling around the face, eye, eyelid or throat) unexplained bruising, reddish or purplish patches on the skin or bleeding more easily than usual as it may indicate that the number of platelets (a type of blood cell responsible for blood clotting) in your blood are reduced severe blistering of the skin or mucous membranes of the lips, eyes, mouth, nasal passages or genitals (signs of a serious skin reaction) purple patches, itching, burning of the skin (signs of inflamed blood vessels) seizures or fits difficulty breathing or swallowing, wheezing or coughing, light-headedness, changes in alertness, skin reddening, facial/throat swelling, blue discoloration of the lips, tongue or skin (signs of severe allergic reaction).	Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

These are serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What FAVIC 500 mg tablet contains

Active ingredient (Main ingredient)	Famciclovir
Other ingredients (Inactive ingredients)	microcrystalline cellulose sodium starch glycollate magnesium stearate hyprolose OPADRY II 85F18378 White (ARTG No 12135).

Tablets do not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What FAVIC looks like

FAVIC 500 are white to off-white, capsule-shaped tablets with ‘FC 500’ on one.

Each pack contains 30 or 56 tablets.

AUST R 159619

Who distributes FAVIC?

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne
Victoria 3121
www.arrotex.com.au

This leaflet was prepared in October 2023

Published by MIMS November 2023

BRAND INFORMATION

Brand name

Favic

Active ingredient

Famciclovir

Schedule

1 Name of Medicine

Famciclovir.

2 Qualitative and Quantitative Composition

Favic tablets come in three strengths and contain either 125 mg, 250 mg or 500 mg of famciclovir.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Favic 125.

White to off-white, round tablet with 'FC' over 125 on one side and blank on the other side.

Favic 250.

White to off-white, round tablet with 'FC' over 250 on one side and blank on the other side.

Favic 500.

White to off-white, capsule-shaped tablet with 'FC 500' on one side and blank on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Favic is indicated for the treatment of herpes zoster infection in adult patients who commence therapy within 72 hours of the onset of rash. Greatest benefit occurs if the drug is started within 48 hours.
Efficacy has not been demonstrated in patients less than 50 years of age, although the occasional younger patient with severe herpes zoster may benefit from therapy with famciclovir. Herpes zoster infection is generally a milder condition in younger patients.
Favic is also indicated for the treatment of recurrent episodes of genital herpes in adults and adolescents 12 years of age and older.
Favic is also indicated for suppression of recurrent genital herpes.
Favic is also indicated for the treatment of recurrent herpes labialis (cold sores) in immunocompetent adult patients.
Favic is also indicated in immunocompromised patients for:
treatment of uncomplicated herpes zoster;
treatment of recurrent herpes simplex;
suppression of recurrent herpes simplex.

4.2 Dose and Method of Administration

Dosage.

Immunocompetent.

Herpes zoster.

The recommended dosage of famciclovir is 250 mg three times daily for seven days. Treatment should be initiated as soon as possible after herpes zoster is diagnosed. Studies have shown famciclovir to be of benefit when started within 72 hours of the onset of rash. Greatest benefit occurs if famciclovir is started within 48 hours.

Recurrent genital herpes infections (HSV).

The recommended dosage is a total dose of 1250 mg famciclovir administered as either: (i) 500 mg statim, then 250 mg 12 hourly for 3 doses or (ii) 125 mg twice each day for 5 days.
Initiation of treatment is recommended during the prodromal period or as soon as possible after onset of lesions.

Suppression of recurrent genital herpes (HSV).

The recommended dose for the suppression of recurrent genital herpes is 250 mg twice daily. As studies conducted to date have not extended beyond 12 months, therapy should be re-evaluated after this period in order to observe possible changes in the natural history of the disease.

Recurrent herpes labialis (cold sores).

The recommended dosage is 1500 mg as a single dose or 750 mg twice daily at 12 hourly intervals for one day (see Section 5 Pharmacological Properties, Clinical trials, Herpes labialis (cold sores)). Initiate therapy at the earliest sign or symptom of a cold sore (e.g. tingling, itching or burning). Treatment was initiated within 1 hour of symptom onset in the recurrent herpes labialis clinical study.
Immunocompromised.

Herpes zoster.

The recommended dosage of famciclovir is 500 mg three times daily for ten days. Initiation of treatment is recommended as soon as possible after rash onset. Studies have shown famciclovir to be of benefit when started within 72 hours of the onset of rash.

Recurrent HSV infections.

For treating herpes simplex infections in immunocompromised adults, the recommended dose is 500 mg twice daily for seven days.
Initiation of treatment is recommended during the prodromal period or as soon as possible after onset of lesions.

Suppression of recurrent genital herpes (HSV) in HIV.

For suppression of recurrent genital herpes infections, a dose of 500 mg twice a day has been shown to be efficacious in HIV patients.

Method of administration.

Famciclovir can be taken without regard to meals (see Section 5 Pharmacological Properties; Section 5.2 Pharmacokinetic Properties, Effect of food).

Dosage adjustment in.

Renal impairment. As reduced clearance of penciclovir is related to reduced renal function, as measured by creatinine clearance, special attention should be given to dosages in patients with impaired renal function. The following modifications in dosage are recommended:

Immunocompetent.

See Table 1.

Immunocompromised.

See Table 2.

As these recommendations are not based on repeated dose data, patients with impaired renal function should be closely monitored for adverse effects. There are insufficient data to recommend a dosage for patients with creatinine clearance less than 10 mL/min/1.73 m².
For a patient on haemodialysis, who has been prescribed famciclovir for conditions other than herpes labialis, a dosage interval of 48 hours is recommended for periods between dialysis. Since 4 hour haemodialysis results in approximately 75% reduction in plasma concentrations of penciclovir, the full adjusted dose (for patients with severe renal impairment) of famciclovir should be administered immediately following dialysis.
Hepatic impairment. Dosage modification is not required for patients with well compensated hepatic impairment.

4.3 Contraindications

Favic is contraindicated in patients:
with known hypersensitivity to famciclovir or any excipient in the formulation; or
who have shown hypersensitivity to penciclovir.

4.4 Special Warnings and Precautions for Use

Efficacy has not been studied in ophthalmic zoster, chicken pox or zoster encephalomyelitis patients.
Genital herpes is a sexually transmitted disease. The risk of transmission is increased during acute episodes. Patients should be advised to use condoms between episodes to reduce the risk of transmission and to avoid sexual intercourse when symptoms are present, even if treatment with an antiviral has been initiated. Genital herpes can also be transmitted in the absence of symptoms through asymptomatic viral shedding. Patients should therefore take appropriate steps for protected intercourse.

Use in hepatic impairment.

Famciclovir has not been studied in patients with severe hepatic impairment. Conversion of famciclovir to the active metabolite penciclovir may be impaired in these patients resulting in lower penciclovir plasma concentrations, and thus possibly a decrease of efficacy of famciclovir (see Section 5 Pharmacological Properties).

Use in renal impairment.

Special attention should be paid to patients with impaired renal function and dosage adjustment may be necessary. Appropriate dosage adjustments for renally impaired patients are provided (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No special precautions are required for elderly patients with normal renal function and patients with mild or moderate hepatic impairment.

Paediatric use.

Safety and efficacy in children has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Effects of other medicinal products on famciclovir.

No clinically significant interactions have been identified with famciclovir or penciclovir.

Probenecid.

Concurrent use of probenecid may result in increased plasma concentrations of penciclovir (active metabolite of famciclovir, see Section 5 Pharmacological Properties).

Other drugs that affect renal physiology.

Could affect plasma levels of penciclovir (active metabolite of famciclovir, see Section 5 Pharmacological Properties).
Evidence from preclinical studies has shown no potential for induction of cytochrome P450.

Zidovudine.

In a phase I study, no significant drug interactions were observed after coadministration of zidovudine and famciclovir.
The conversion of the inactive metabolite 6-deoxy penciclovir to penciclovir is catalysed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur. Clinical interaction studies of famciclovir with cimetidine and promethazine, in vitro inhibitors of aldehyde oxidase, did not show relevant effects on the formation of penciclovir. However, raloxifene, the most potent aldehyde oxidase inhibitor observed in vitro, could affect the formation of penciclovir and thus the efficacy of famciclovir. When raloxifene is co-administered with famciclovir, the clinical efficacy should be monitored.

Effects of famciclovir on other medicinal products.

Although famciclovir is only a weak inhibitor of aldehyde oxidase in vitro, interactions with drugs metabolized by aldehyde oxidase could potentially occur. Evidence from preclinical studies has shown no potential for induction of cytochrome P450 enzymes or inhibition of CYP3A4.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Testicular toxicity was observed in rats, mice and dogs following repeated administration of famciclovir or penciclovir. Testicular changes included atrophy of seminiferous tubules, reduction in sperm count and/or increased incidence of sperm with abnormal morphology or reduced motility. The degree of testicular toxicity was related to dose and duration of exposure and tended to reverse after the cessation of dosing. In male rats, decreased fertility was observed after 10 weeks dosing at 500 mg/kg/day, or approximately 3 to 20 times the human systemic exposure (AUC). Testicular toxicity was also seen in mice and dogs following chronic administration at exposures to penciclovir ranging from 2 to 14 times the human systemic exposure (AUC). However, there were no clinically significant effects on sperm count, morphology and motility in male patients receiving 250 mg famciclovir b.i.d. for 18 weeks. Famciclovir had no effect on fertility in female rats at doses of up to 1000 mg/kg/day, approximately 4 to 27 times the human systemic exposure (AUC).
(Category B1)
Famciclovir was tested for effects on embryo-foetal development in rats and rabbits at oral doses up to 1000 mg/kg/day (approximately 4 to 27 times and 2 to 12 times the human systemic exposure to penciclovir in rats and rabbits, respectively [AUC]), and intravenous doses of 360 mg/kg/day in rats (1.9 to 12 times the human dose based on body surface area [BSA] comparisons) or 120 mg/kg/day in rabbits (1.2 to 7.1 times the human dose [BSA]). No adverse effects were observed on embryo-foetal development. Similarly, no adverse effects were observed following intravenous administration of penciclovir to rats (80 mg/kg/day, 0.4 to 2.6 times the human dose [BSA]) or rabbits (60 mg/kg/day, 0.6 to 3.6 times the human dose [BSA]). Although animal studies have not shown any embryotoxic or teratogenic effects with famciclovir or penciclovir, the safety of famciclovir in human pregnancy has not been established. Famciclovir should therefore not be used during pregnancy unless the potential benefits are considered to outweigh the potential risks associated with treatment.
Famciclovir should not be used by nursing mothers unless the potential benefits are considered to outweigh the potential risks associated with treatment. Following oral administration of famciclovir to lactating rats, penciclovir was excreted in milk at concentrations higher than those seen in plasma. There is no information on excretion in human milk.

4.7 Effects on Ability to Drive and Use Machines

Patients who experience dizziness, somnolence, confusion or other central nervous system disturbances while taking famciclovir should refrain from driving or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

Famciclovir has been well tolerated in human studies. Headache, fatigue and nausea have been reported in clinical trials. These were generally mild or moderate and occurred at a similar incidence in patients receiving placebo treatment. Confusion, predominantly in the elderly, has been reported rarely. See Table 3.
The following adverse events occurred during the clinical trial in recurrent herpes labialis. See Tables 4-6.
Famciclovir has also been well tolerated in immunocompromised patients. Undesirable effects reported from clinical studies were similar to those reported in the immunocompetent population.

Post-marketing data.

In addition to the adverse events reported in the clinical trials, the following events have been reported rarely (rare: ≥ 10,000, < 1/1,000; very rare: < 1/10,000) in post-marketing surveillance:

Blood and lymphatic system disorders.

Very rare: Thrombocytopenia.

Psychiatric disorders.

Uncommon: Confusion (predominantly in the elderly).
Rare: Hallucinations.

Nervous system disorders.

Very common: Headache.
Common: Dizziness.
Uncommon: Somnolence (predominantly in the elderly).
Not known: Seizure.

Cardiac disorders.

Rare: Palpitations.

Gastrointestinal disorders.

Common: Vomiting, nausea, abdominal pain, diarrhoea.

Hepatobiliary disorders.

Common: Liver function test abnormal.
Rare: Jaundice cholestatic

Immune system disorders.

Not known: Anaphylactic shock, anaphylactic reaction.

Skin and subcutaneous tissue disorders.

Common: Rash, pruritus.
Uncommon: Angioedema (e.g. face oedema, eyelid oedema, periorbital oedema, pharyngeal oedema), urticaria.
Very rare: Serious skin reactions (e.g. erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis).
Not known: Hypersensitivity vasculitis.

Musculoskeletal disorders.

Very rare: arthralgia, myalgia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Overdose experience with famciclovir is limited. A report of accidental acute overdosage (10.5 g) was asymptomatic. In a report of chronic use (10 g/day for two years), famciclovir was well tolerated.
Symptomatic and supportive therapy should be given as appropriate. Acute renal failure has been reported rarely in patients with underlying renal disease. The famciclovir dosage in these patients had not been appropriately reduced for the level of renal function.
Penciclovir is dialysable; plasma concentrations are reduced by approximately 75% following 4 hour haemodialysis.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Famciclovir is the oral form of penciclovir. Famciclovir is rapidly converted in vivo into penciclovir, which has demonstrable in vitro activity against herpes simplex viruses (HSV types 1 and 2) and varicella zoster virus (VZV). The antiviral effect of orally administered famciclovir has been demonstrated in several animal models: this effect is due to in vivo conversion to penciclovir.
Penciclovir targets virus-infected cells where it is rapidly converted into penciclovir-triphosphate (mediated via virus-induced thymidine kinase). The triphosphate inhibits viral DNA polymerase by competition with deoxyguanosine triphosphate and is incorporated into the extending DNA chain, preventing significant chain elongation. Consequently, viral DNA synthesis and, therefore, viral replication are inhibited.
This triphosphate persists in infected cells in excess of 12 hours. The long intracellular half-life of penciclovir triphosphate ensures prolonged antiviral activity, as demonstrated in cell cultures with HSV-1 and HSV-2 and in animal studies.
Penciclovir is only readily phosphorylated in virus-infected cells. In uninfected cells treated with penciclovir, concentrations of penciclovir-triphosphate are only barely detectable. Accordingly, uninfected cells are unlikely to be affected by therapeutic concentrations of penciclovir.
The most common form of resistance encountered with aciclovir among HSV strains is a deficiency in the production of the thymidine kinase (TK) enzyme. Such TK deficient strains would be expected to be cross-resistant to both penciclovir and aciclovir. However, penciclovir has been shown to be active against a clinically isolated acyclovir-resistant herpes simplex type 1 strain with an altered DNA polymerase.
The results from penciclovir and famciclovir patient studies, including studies of up to four months' treatment with famciclovir, showed that no resistance occurred as a result of treatment with either famciclovir or penciclovir. Penciclovir-resistant isolates were found at the start of treatment or in the placebo groups in 0.25% of the 1976 total isolates from HSV and VZV (5/1976), and in 0.19% of the 533 virus isolates from immunocompromised patients (1/533).

Clinical trials.

Herpes zoster.

Placebo-controlled trial. Famciclovir was studied in a placebo-controlled, double-blind trial of 419 otherwise healthy patients with uncomplicated herpes zoster who were treated with famciclovir 500 mg t.i.d. (n=138), famciclovir 750 mg t.i.d. (n=135) or placebo (n=146). Treatment was begun within 72 hours of initial lesion appearance and therapy was continued for 7 days.

Dermatology and virology.

The times to full crusting, loss of vesicles, loss of ulcers and loss of crusts were shorter for famciclovir 500 mg-treated patients than for placebo-treated patients in the overall study population. The median time to full crusting in famciclovir 500 mg-treated patients was 5 days compared to 7 days in placebo-treated patients. No additional efficacy was demonstrated with the higher dose of famciclovir (750 mg t.i.d.) when compared to famciclovir 500 mg t.i.d. In the total population, 65.2% of patients had a positive viral culture at some time during their acute infection. Patients treated with famciclovir 500 mg had a shorter median duration of viral shedding (time to last positive viral culture) than did placebo-treated patients (1 day and 2 days, respectively).

Acute pain and postherpetic neuralgia.

There were no overall differences in the duration of acute pain (i.e. pain before rash healing) between famciclovir and placebo-treated groups. In addition, there was no difference in the incidence of postherpetic neuralgia (i.e. pain after rash healing) between the treatment groups. In the 186 patients (44.4% of total study population) who did develop postherpetic neuralgia, the median duration of postherpetic neuralgia was shorter in patients treated with famciclovir 500 mg than in those treated with placebo (63 days and 119 days, respectively).
Active-control trial. A second double-blind controlled trial in 545 otherwise healthy patients with uncomplicated herpes zoster treated within 72 hours of initial lesion appearance compared famciclovir 250 mg t.i.d. (n=134), famciclovir 500 mg t.i.d. (n=134), famciclovir 750 mg t.i.d. (n=138) and aciclovir 800 mg 5 times per day (n=139) for 7 days. In this study, patients treated with famciclovir at each dose and aciclovir had comparable times to full lesion crusting and times to loss of acute pain. There were no statistically significant differences in the time to loss of postherpetic neuralgia between famciclovir and aciclovir-treated groups.
Higher doses of famciclovir (500 mg t.i.d.; 750 mg t.i.d.) have not been shown to confer greater benefit. The minimum effective dose of famciclovir in the treatment of herpes zoster has not been established.
Immunocompromised. A double-blind, controlled clinical trial was conducted in 148 oncology and transplant patients with herpes zoster infections who received famciclovir 500 mg t.i.d. (n=71) or aciclovir 800 mg 5 times per day (n=77) for 10 days. Patients started study medication within 72 hours of rash onset. Overall famciclovir and aciclovir showed comparable efficacy. The median times to full crusting and complete healing were 8 and 20 days for the famciclovir group and 9 and 21 days for the aciclovir group. The median times to loss of all pain were 14 and 17 days for the famciclovir and aciclovir groups, respectively. Withdrawal due to dissemination of zoster and continued new lesion formation beyond 10 days of onset was reported in 7% of the famciclovir group and 9% of the aciclovir group.

Genital herpes.

Placebo-controlled trials.

In two placebo-controlled trials, 626 otherwise healthy patients with a recurrence of genital herpes were treated with famciclovir 125 mg b.i.d. (n=160), famciclovir 250 mg b.i.d. (n=169), famciclovir 500 mg b.i.d. (n=154) or placebo (n=143) for 5 days. Treatment was initiated within 6 hours of either symptom onset or lesion appearance. In the two studies combined, the median time to healing in famciclovir 125 mg-treated patients was 4 days compared to 5 days in placebo-treated patients. The median time to cessation of viral shedding was 1.8 vs 3.4 days in famciclovir 125 mg and placebo recipients, respectively. The median time to loss of all symptoms was 3.2 days in famciclovir 125 mg-treated patients vs. 3.8 days in placebo-treated patients. When used to treat acute recurrent genital herpes, no additional efficacy was demonstrated with higher doses of famciclovir (250 mg b.i.d. or 500 mg b.i.d.) when compared to famciclovir 125 mg b.i.d.
In two placebo controlled suppression studies, immunocompetent patients (n=934) with at least six recurrences of genital herpes per year received 125 mg t.i.d. (n=233), 250 mg b.i.d. (n=236), 250 mg t.i.d. (n=232) or placebo (n=233) for 52 weeks. Treatment was initiated during an asymptomatic period. Among those who received famciclovir 250 mg b.i.d., the proportion of patients who remained free from virologically confirmed recurrence at the 12 month end point was 68% in one trial and 72% in the second trial compared with approximately 21% in the placebo groups. Median days to first clinically confirmed recurrence for the famciclovir 250 mg b.i.d. treatment groups were > 365 days for the famciclovir 250 mg b.i.d. treatment groups compared to 67 days for the placebo treated group in one of the studies and 336 days for the famciclovir groups compared to 47 days for the placebo group in the second study.

Short-course vs. standard-course therapy (FaST study).

In a randomised, double-blind, non-inferiority, multi-centre study (59 sites in Australia and 7 in Canada), famciclovir 500 mg statim then 250 mg bd for 2 days (short-course) was compared to the standard regimen of 125 mg bd for 5 days in the treatment of adult patients with recurrent genital herpes. HIV-infected patients were eligible if CD4 ≥ 500 cells/microL and/or CD4% ≥ 25%.
The study was designed to treat and follow each eligible patient for two complete and consecutive recurrences. A total of 1038 recurrences occurred in 616 patients that were randomised and treated. Treatment was initiated by patients within 12 hours of development of a lesion or onset of symptoms.
Patients attended for assessment within 24 hours and then 5.5 days following initiation of treatment. A daily diary was used to record treatment compliance, progression of lesions and symptoms, functional impact and side effects from the treatment.
The primary endpoint was the estimated probability of being not lesion-free at 5.5 elapsed days (132 hours) after patient self-initiation of therapy. The estimated probability was 24.4% for recurrences treated with the 2-day regimen and was 27.6% for recurrences treated with the 5-day regimen. The upper one-sided 97.5% confidence limit of the treatment difference was 1.7% which was within the pre-defined margin for claiming non-inferiority. Non-inferiority was maintained in five sensitivity analyses, confirming a robust result.
Over the course of treatment, there were no differences between the mean symptom and functional impact scores for either the famciclovir short-course or the standard-course treatment groups.
The study concluded that the 2-day famciclovir regimen was equivalent to the 5-day regimen in the treatment of adult patients with recurrent genital herpes.

Immunocompromised.

A randomised, double-blind controlled trial in 293 HIV-infected patients with a recurrence of genital herpes compared famciclovir 500 mg b.i.d. (n=150) and aciclovir 400 mg 5 times per day (n=143) for 7 days. Treatment was initiated within 48 hours of lesion onset. Famciclovir and aciclovir were equally effective in prevention of new lesion formation while patients were receiving treatment. Efficacy in the three main time to event parameters were also comparable. The median times to complete healing of lesions, cessation of viral shedding and loss of lesion pain were 7 days, 2 days and 3 days for both the famciclovir and aciclovir treatment groups, respectively.
A further double-blind, placebo-controlled crossover study was conducted in 48 patients with HIV to assess famciclovir (500 mg b.i.d.) in the suppression of HSV recurrence for 8 weeks. Famciclovir showed statistically significant superiority over placebo in the efficacy parameters measured. There was an approximate 10-fold reduction in the percentage of days with HSV shedding (p=0.0003) and a 6.7-fold reduction in the proportion of patients with HSV shedding from anogenital sites (p=0.0065) in the famciclovir treated group. There was also an 8.7-fold reduction in the proportion of patients with HSV shedding from any site. Overall in the famciclovir group, the proportion of days of asymptomatic, symptomatic, subclinical or lesional HSV shedding from any site was significantly reduced compared to placebo (p=0.0012).
In the famciclovir treatment group there was a 2.6-fold reduction in the percentage of days with lesions (p=0.0101), and a 3.6-fold reduction in the percentage of days with lesions/symptoms (p=0.0089) over the placebo group.

Herpes labialis (cold sores).

In one large placebo-controlled trial, 701 immunocompetent adults with recurrent herpes labialis were treated with famciclovir 1500 mg once (n=227), famciclovir 750 mg b.i.d. (n=220) or placebo (n=254) for 1 day. As well, patients also had to be in good general health, aged at least 18 years, have normal renal and hepatic function, had prior pregnancy tests if they were females of reproductive age, and have experienced 3 or more episodes of cold sores in the preceding 12 months. Patients were required to have a history of prodromal symptoms preceding at least 50% of the recurrent episodes, and at least 50% of these episodes had to have progressed to the vesicular lesion stage. Women of childbearing potential had to agree to use reliable birth control measures during the study. Pregnant or breast-feeding women were excluded. Patients were excluded if they had received an investigational drug in the 4 weeks prior to the study, had been previously vaccinated against herpes, or were using a topical immunosuppressive agent on or near the face or a systemic immunosuppressive agent within 1 month of screening. Patients were also excluded if they were immunosuppressed due to underlying disease or concomitant treatment had a recent history of drug or alcohol abuse, were suffering from inflammatory skin diseases (e.g. eczema or dermatitis) that would interfere with the assessment of lesions, or were allergic or hypersensitive to products containing aciclovir, penciclovir, famciclovir or other nucleoside analogs.
Patients were instructed to take the first dose of study medication within 1 hour of symptom onset. However, some patients commenced treatment after 1 hour of onset of symptoms. Both famciclovir regimens significantly reduced time to healing of primary vesicular herpes labialis lesions (the primary efficacy variable) in the modified ITT population compared with placebo. The median time to healing in famciclovir 1500 mg single-dose treated patients was 4.4 days compared to 4.0 days in famciclovir 750 mg bid and 6.2 days in placebo-treated patients. This translates to treatment effects of 1.8 (CI 95% 0.9, 2.7) and 2.2 (CI 95% 1.3, 3.1) days, respectively. A single 1500 mg dose of famciclovir reduced the time to resolution of pain and tenderness (median time 1.7 days versus 2.9 days) compared with placebo and was marginally more effective than famciclovir 750 mg b.i.d. (median time 2.1 days).

5.2 Pharmacokinetic Properties

Absorption.

Famciclovir is the oral prodrug of penciclovir. Following oral administration, famciclovir is rapidly and extensively absorbed and converted to the antivirally active compound penciclovir. Bioavailability of penciclovir after oral famciclovir is 77%. Mean peak plasma concentrations of penciclovir following a 125 mg, 250 mg, 500 mg and 750 mg oral dose of famciclovir were 0.8 microgram/mL, 1.6 microgram/mL, 3.3 microgram/mL and 5.1 microgram/mL respectively, and occurred at a median time of 45 minutes post-dose. There are no data on the pharmacokinetics of the 1500 mg single dose.

Distribution.

Plasma concentration-time curves of penciclovir are similar following single and repeat (b.i.d. and t.i.d.) dosing and there is no accumulation of penciclovir on repeated dosing. Penciclovir and its 6-deoxy precursor are poorly (< 20%) bound to plasma proteins.

Excretion.

Famciclovir is eliminated principally as penciclovir and its 6-deoxy precursor, which are excreted in urine. No unchanged famciclovir has been detected in urine. Tubular secretion and glomerular filtration contribute to renal elimination of the compound. The terminal plasma half-life of penciclovir after both single and repeat dosing with famciclovir is approximately 2.0 hours. There is no accumulation of penciclovir on repeated dosing with famciclovir.

Effect of food.

Penciclovir C_max was decreased by approximately 50% and T_max was delayed by 1.5 h when a capsule formulation of famciclovir was administered 30 minutes after food. When famciclovir tablets were administered 30 minutes after food, penciclovir C_max was reduced by approximately 20% and T_max was delayed by 0.75 h. The systemic availability (AUC) of penciclovir following either preparation was unaffected. The clinical consequences of these effects on plasma concentration are unknown.

Characteristics in special populations.

Patients with herpes zoster infection.

Herpes virus infection does not significantly alter the pharmacokinetics of penciclovir measured after the oral administration of famciclovir.

Renal impairment.

Plasma clearance, renal clearance and plasma elimination rate constant decreased linearly with reductions in renal function. A dosage interval adjustment is recommended for patients with renal insufficiency (see Section 4.2 Dose and Method of Administration).

Hepatic impairment.

Well-compensated chronic liver disease (chronic hepatitis [n=6], chronic ethanol abuse [n=8] or biliary cirrhosis [n=1]) has no effect on the extent of availability (AUC) of penciclovir following a single dose of 500 mg famciclovir. No dose adjustment is recommended for patients with well-compensated hepatic impairment (see Section 4.2 Dose and Method of Administration, Hepatic impairment; Section 4.4 Special Warnings and Precautions for Use). However, there was a 43% decrease in penciclovir mean maximum plasma concentration and the time to maximum plasma concentration was increased by a median of 0.75 h in patients with hepatic insufficiency compared to normal volunteers. The pharmacokinetics have not been evaluated in patients with severe uncompensated hepatic impairment.

Elderly patients.

Based on cross-study comparisons of single dose studies, the mean penciclovir AUC was approximately 30% larger, half-life 23% longer and penciclovir body weight adjusted renal clearance reduced by 19% in healthy elderly male volunteers (n=18, aged 65 to 79 years) compared to younger volunteers. Some of this difference may be due to differences in renal function between the two groups. No dosage adjustment based on age is recommended unless renal function is impaired (see Section 4.2 Dose and Method of Administration).

HIV patients.

Extrapolated data from a study (n=8) where famciclovir was given as a single dose resulted in a mean AUC of 24 microgram.h/mL, which is similar to that obtained in healthy subjects.

Transplant patients.

In a study of allogeneic bone marrow transplant or peripheral blood stem cell transplant or allogeneic renal transplant patients (n=21), intravenous penciclovir for one month was followed by oral use of famciclovir. The doses of penciclovir and famciclovir were adjusted according to creatinine clearance. During repeat dosing with famciclovir, the AUC of penciclovir was found to be 66 microgram.h/mL in subjects with creatinine clearance greater than 50 mL/min. No safety concerns were identified despite the higher than normal AUCs reported, and additional dosage adjustment in renal transplant patients is not recommended.

5.3 Preclinical Safety Data

Data presented below include reference to area under the plasma concentration curve (24 hour AUC) for penciclovir in humans following the lowest and highest recommended doses for famciclovir (i.e. penciclovir AUC of 4.5 microgram.h/mL at 125 mg b.i.d. for acute recurrent genital herpes, and a penciclovir AUC of 27 microgram.h/mL at 500 mg t.i.d. for herpes infections in immunocompromised patients). This is based on the assumption that the pharmacokinetics in immunocompetent subjects are similar to the pharmacokinetics in immunocompromised subjects, as shown in the study on HIV patients (see Section 5.2 Pharmacokinetic Properties). If the higher values of AUC obtained in the renal transplant patients were used as a basis for comparison, the multiples specified here would be decreased. Exposures in animal studies are expressed as multiples of human exposures at the highest and lowest dosing schedules based on penciclovir AUC or body surface area.

Genotoxicity.

Famciclovir and penciclovir (the active metabolite of famciclovir) were tested for genotoxic potential in a series of in vitro and in vivo assays. Famciclovir showed no genotoxic potential in a series of assays for gene mutations, chromosomal damage and DNA damage. Penciclovir was positive in the L5178Y mouse lymphoma assay for gene mutations/chromosomal damage, caused chromosomal aberrations in human lymphocytes in vitro and was positive in a mouse micronucleus assay in vivo when administered IV at doses toxic to bone marrow.

Carcinogenicity.

The carcinogenic potential of famciclovir was evaluated in 2 year dietary studies in rats and mice. A significant increase in the incidence of mammary adenocarcinoma was seen in female rats receiving 600 mg/kg/day. No increases in tumour incidences were reported for male rats treated at doses of up to 240 mg/kg/day or in mice of either sex at doses of up to 600 mg/kg/day. At the no effect levels of 240 and 200 mg/kg/day in male and female rats, the daily exposures to penciclovir based on AUC were about 40 and 29 microgram.h/mL respectively, or approximately 1 to 8 times the human systemic exposures at 500 mg t.i.d or 125 mg b.i.d. Systemic exposures at the no effect dose in male and female mice were 65 and 46 microgram.h/mL respectively, or approximately 2 to 12 times the human systemic exposure (AUC).

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following excipients: sodium starch glycollate, microcrystalline cellulose, hyprolose, magnesium stearate, and Opadry II complete film coating system 85F18378 white. The tablets are gluten free.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.