Consumer medicine information

ZOVIRAX 400 mg Tablets

Aciclovir

BRAND INFORMATION

Brand name

Zovirax

Active ingredient

Aciclovir

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ZOVIRAX 400 mg Tablets.

What is in this leaflet

This leaflet answers some common questions about Zovirax® 400 mg tablets (Zovirax 400). It does not contain all of the available information.

Reading this leaflet does not take the place of talking to your doctor or pharmacist.

Taking any medicine involves some risk. It is possible that all risks associated with this medicine might not have been detected, despite proper testing. Only your doctor or pharmacist is able to weigh up all of the relevant facts, and you should consult them if you have any queries.

If you have any concerns about taking Zovirax 400 ask your doctor or pharmacist.

Keep this information.

You may want to read it again. This leaflet provides information about Zovirax 400. The statements that are made in this leaflet cannot be applied to any other medicine, even those that are similar or appear to contain the same ingredients.

What Zovirax 400 is used for

Zovirax 400 is used for the treatment of shingles (herpes zoster).

How does Zovirax 400 work

Aciclovir (the active ingredient in Zovirax 400) belongs to a group of medicines called "anti-virals". Zovirax 400 works by stopping the production of the herpes virus. This reduces the length and severity of an outbreak of herpes. Zovirax 400 does not get rid of the virus from your body.

Your doctor may, however, have prescribed Zovirax 400 for a different use to that described above.

If you have any questions about why you are taking Zovirax 400 ask your doctor or pharmacist. Your doctor or pharmacist will be able to provide you with more information.

Before you take Zovirax 400

Zovirax 400 is not suitable for everyone.

Be sure that your doctor knows about the following before you take Zovirax 400:

  1. If you are allergic to:
    - Aciclovir (the active ingredient in Zovirax 400) or valaciclovir.
    - Any other ingredient listed at the end of this leaflet.
  2. If you are pregnant, or become pregnant while using Zovirax 400, or are breastfeeding.
  3. If you suffer from:
    - A kidney or liver condition, or
    - A blood condition, or
    - Any condition affecting your brain.

Taking other medicines

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

Some medicines and ZOVIRAX 400 may interfere with each other. These include:

  • medicines used to prevent gout or gouty arthritis such as probenecid.
  • fluid tablets (diuretics).
  • medicines used to treat gastric ulcers or reflux such as cimetidine.
  • medicines used prevent rejection of transplanted organs such as mycophenolate mofetil.

These medicines may be affected by ZOVIRAX or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

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

When you must not take Zovirax 400

Do not take Zovirax 400 after the expiry date printed on the pack.

Do not take Zovirax 400 if the packaging shows signs of tampering.

Do not take Zovirax 400 to treat any other conditions unless advised by your doctor.

Do not give Zovirax 400 to anyone else, even if their symptoms seem similar to yours.

Taking Zovirax 400

Take Zovirax 400 as directed by your doctor or pharmacist. Never change the dose yourself.

Your doctor and pharmacist will be able to tell you:

  • how many tablets to take at each dose.
  • how many doses to take each day.
  • when to take each of your doses.

The label on the pack that the tablets were supplied in will give the same information. If there is something that you do not understand ask either your doctor or pharmacist.

The usual dose of Zovirax 400 is two 400 mg tablets every four hours while awake (a total of ten tablets daily) for 7 days.

The shingles compliance pack will help you remember to take the tablets at the correct times.

Your doctor may also vary the Zovirax 400 dosage for other medical reasons.

If you have any questions about the dose that you have been prescribed you should ask your doctor or pharmacist.

How to take Zovirax 400

Your Zovirax 400 tablets may be swallowed whole with a glass of water, or dispersed in a quarter of a glass of water (about 50 mL) and then swallowed.

If you forget to take your dose

If you have just missed your scheduled dose, take it as soon as you remember and continue as before.

If you have forgotten to take one dose of Zovirax 400 and it is almost time to take your next scheduled dose, then skip the dose you have missed, and continue taking your Zovirax 400 as directed by your doctor or pharmacist.

If you have forgotten to take more than one dose contact your doctor or pharmacist for advice.

Do not take a double dose to make up for the dose that you have missed.

If you have trouble remembering when to take your medicine, as your pharmacist for some hints.

In case of overdose

Immediately contact your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to accident and emergency at your nearest hospital, if you think that you may have taken too much, or if anyone else may have taken too much Zovirax 400. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

While you are taking Zovirax 400

Drink plenty of plain fluids. Your doctor or pharmacist will be able to tell you whether there are any special instructions while you are taking Zovirax 400.

See your doctor if you feel that your condition is not improving or getting worse.

Driving and using machines

Some side effects such as feeling drowsy or sleepy may impair your ability to concentrate and react. Make sure you are not affected before you drive or operate machinery

When to stop taking Zovirax 400

Do not stop taking Zovirax 400 just because you feel better. It is important that you complete your course of tablets to effectively treat the shingles.

Your doctor will advise you when to stop taking Zovirax 400. If you are unsure whether you should stop taking Zovirax 400 talk to your doctor or pharmacist.

Side Effects

All medicines can have some side effects. Sometimes they are serious. Most of the time they are not.

Zovirax 400 helps most people with shingles. In a few people it may have some unwanted side effects.

Be sure that your doctor or pharmacist knows as soon as possible if you do not feel well while you are taking Zovirax 400. Often it is difficult to tell the difference between side effects of medication and symptoms of the underlying illness.

Tell your doctor if you notice any of the following:

  • Severe allergic reactions (rare). Signs include: itchy, bumpy rash (hives), swelling sometimes of mouth causing difficulties breathing, collapse. Contact your doctor immediately if you get these symptoms. Stop taking Zovirax.
  • Nausea, vomiting, diarrhoea, stomach pain, headache, dizziness, confusion, hallucinations, seizures, fatigue, itching, skin reaction after sunlight exposure, and fever.

Less common side effects include:

  • Hair loss, itchy, bumpy rash (urticaria).
  • Chest pain, shortness of breath, aching.
  • Constipation.
  • Taste disturbance.
  • Liver disorders.
  • Vertigo, difficulty sleeping.

A small number of patients have had other unwanted effects after taking Zovirax 400.

There is no evidence that Zovirax 400 is addictive.

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

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by this list of possible side-effects. You may not experience any of them.

After taking Zovirax 400

If your doctor advises you to stop taking Zovirax 400 ask your pharmacist what to do with any remaining tablets.

Storage

Keep your tablets in the pack that they were supplied in.

Keep Zovirax 400 in a cool, dark and dry place where the temperature stays below 30°C. Do not store Zovirax 400 in the bathroom or near a sink. Heat and dampness may affect Zovirax 400.

Keep Zovirax 400, and all other medicines, where children cannot reach them.

Do not leave Zovirax 400 in the car on hot days.

Product description

What Zovirax 400 looks like

Zovirax 400 tablets are white, concave, shield-shaped, film-coated tablets, branded GXCF5 on one side and plain on the other. They are available in packs of 100 tablets.

The information provided applies only to: Zovirax 400 mg tablets.

Ingredients

Zovirax 400 contains 400 mg of the active ingredient aciclovir.

Zovirax 400 also contains:

  • cellulose-microcrystalline
  • povidone
  • sodium starch glycollate
  • aluminium magnesium silicate
  • magnesium stearate
  • macrogol 8000
  • coating opadry Y-1-7000 concentrate

Manufacturer

Zovirax 400 tablets are supplied in Australia by:
GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street
Abbotsford, Victoria, 3067

AUST R 51428

This leaflet was prepared on 13 February 2015.

Zovirax® is a registered trade mark of the GlaxoSmithKline group of companies.

© 2013 GlaxoSmithKline.

Version 5.0

Published by MIMS July 2015

BRAND INFORMATION

Brand name

Zovirax

Active ingredient

Aciclovir

Schedule

S4

 

Name of the medicine

Aciclovir.

Excipients.

Zovirax Dispersible Tablets (200 mg, 400 mg and 800 mg).

Microcrystalline cellulose, aluminium magnesium silicate, sodium starch glycollate, povidone, magnesium stearate, Opadry Complete film coating system White Y-1-7000 and macrogol 8000.

Zovirax 200 mg Tablets.

Microcrystalline cellulose, lactose monohydrate, magnesium stearate, povidone and sodium starch glycollate.

Zovirax 400 mg and 800 mg Tablets.

Microcrystalline cellulose, magnesium stearate, povidone and sodium starch glycollate.

Description

Chemical name: 9-((2-hydroxyethoxy) methyl) guanine. CAS: 59277-89-3. Aciclovir is a synthetic acyclic purine nucleoside analogue. It is a white crystalline powder slightly soluble in water and practically insoluble in most organic solvents.

Pharmacology

Microbiology.

Aciclovir is an antiviral agent which is active in vitro against herpes simplex virus (HSV) types I and II and varicella zoster virus (VZV), the latter being considerably less sensitive. The relationship between the level of in vitro sensitivity of herpes viruses to aciclovir and clinical response to therapy has not been adequately established. Development of resistance by HSV to aciclovir has been documented. Aciclovir needs to be phosphorylated to the active compound, aciclovir triphosphate, in order to become active against the virus. Such conversion is very limited in normal cells and, in addition, cellular DNA polymerase is not very sensitive to the active compound. However, in infected cells, HSV or VZV coded thymidine kinase facilitates the conversion of aciclovir to aciclovir monophosphate, which is then converted to aciclovir triphosphate by cellular enzymes. Aciclovir triphosphate acts as an inhibitor of and substrate for the herpes specified DNA polymerase, preventing further viral DNA synthesis.

Pharmacokinetics.

Aciclovir is only partially and variably absorbed from the gut. Estimated bioavailability following a dose of 200 mg is about 20% and decreases to about half of this with an 800 mg dose. Mean steady-state peak and trough concentrations during dosage of 200 mg administered four hourly were 0.49 (range 0.47-0.54) microgram/mL and 0.31 (range 0.18-0.41) microgram/mL, respectively, and after 800 mg six hourly were 1.43 (range 0.66-1.8) microgram/mL and 0.55 (range 0.14-1.10) microgram/mL, respectively. Both peaks and trough levels following repeated doses in adults over 60 years of age are considerably higher than in young adults, apparently because of the reduced renal function in the elderly.
Following oral administration, the mean plasma half-life of aciclovir in volunteers and patients with normal renal function ranges from 2.5 to 3.3 hours. Approximately 60% of the drug is excreted unchanged by the kidney by glomerular filtration and tubular excretion. When aciclovir is given after probenecid, the terminal half-life and the area under the plasma concentration time curve are extended. 9-Carboxymethoxymethylguanine is the major metabolite of aciclovir and accounts for 10-15% of the dose excreted in the urine following i.v. administration.
In children aged 0-3 months the terminal plasma half-life is approximately 4 hours. However, experience is insufficient at present to recommend therapy for this age group.
Because aciclovir is excreted mainly by the kidneys, its total body clearance in the elderly (> 60 years of age) declines due to decreased renal function. The terminal half-life of aciclovir in the elderly is approximately 4.6 hours. It is important to maintain adequate hydration in elderly patients taking high oral doses.
In patients with chronic renal failure, the mean terminal half-life following i.v. administration was found to be 19.5 ± 5.9 S.D. hours. The mean aciclovir half-life during haemodialysis was 5.7 hours. Plasma aciclovir levels dropped approximately 60% during dialysis.
Studies have shown no apparent changes in the pharmacokinetic properties of aciclovir or zidovudine when both are administered simultaneously to HIV infected patients.
Dosage adjustment for Zovirax Tablets is recommended in renal impairment (see Dosage and Administration). Plasma protein binding is low (9 to 33%).

Indications

Zovirax tablets are indicated for use in adult patients for:
The treatment of first episode (primary or nonprimary) genital herpes and the management of recurrent episodes of genital herpes in certain patients.
The treatment of acute attacks of herpes zoster (shingles) when the duration of rash is less than 72 hours.
The management of patients with advanced symptomatic HIV disease (CD4+ counts < 150 x 106/L).

Genital herpes.

Initial episodes.

The duration of viral shedding is reduced very significantly; the duration of pain and time to healing are also reduced. The promptness of initiation of therapy and/or the patient's prior exposure to herpes simplex virus may influence the degree of benefit from therapy.
Intravenous aciclovir should be considered in patients in whom prostration, central nervous system involvement or inability to take oral medication requires hospitalisation and initiation of more aggressive management.
Zovirax does not prevent the establishment of latency in primary episodes.

Recurrent episodes.

Suppression.

In patients with frequent recurrences, suppressive therapy prevents or reduces the frequency and/or severity of recurrences in a high proportion of patients. Abortive episodes (prodromal symptoms without vesicle formation) and occasional breakthrough episodes may, however, continue to occur during suppressive therapy.
Suppressive therapy is not considered appropriate for patients in whom attacks are mild, last for short periods and/or occur infrequently (e.g. less frequently than once a month).
Zovirax is effective only during the period of intake and has no residual beneficial effect. It does not eradicate the body viral pool. Following cessation of therapy, the time to onset of recurrences, their frequency, severity and duration remain generally unaffected. Some patients may experience increased severity of the first episode following cessation of therapy.
The risk of inducing viral resistance and of potential long-term adverse effects (see Precautions, Carcinogenic potential, Mutagenic potential and Effects on fertility) should be weighed carefully before initiating suppressive therapy.
Asymptomatic cases of genital herpes are known to shed the virus with a high frequency. However, at present only limited data are available on the extent and frequency of viral shedding in patients receiving suppressive therapy. Therefore, if therapy with Zovirax Tablets is being used in the prenatal period (see Precautions, Use in pregnancy), it should not be assumed that viral shedding has ceased. Pregnancy should be managed according to considerations normally applicable to patients with genital herpes.
In view of the complex and variable natural history of genital herpes, suppressive therapy should be interrupted periodically to ascertain whether the disease has undergone spontaneous change in frequency or severity (see Dosage and Administration).

Intermittent treatment.

For certain patients, intermittent short-term treatment of recurrences is effective. Although the average patient would derive limited benefits from such treatment, a minority of patients who have experienced severe, prolonged recurrent episodes or recurrences complicated by eczema, burns or immunosuppression may experience more appreciable benefits. In those patients, intermittent treatment may be more appropriate than suppressive therapy when recurrences are infrequent.

Herpes zoster.

In controlled trials Zovirax Tablets were shown to reduce acute pain and rash progression in adult patients of all ages with herpes zoster in whom the duration of rash was less than 72 hours. Zovirax Tablets appeared to be relatively less effective in younger adults, in whom herpes zoster is generally a milder disease.
In ophthalmic zoster, oral Zovirax has been shown to reduce the incidence of stromal keratitis and both the incidence and severity of anterior uveitis, but not other ocular complications or acute pain.

Note.

In immunocompetent patients with very severe herpes zoster, immunocompromised patients, or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing.

Patients with advanced symptomatic HIV disease (CD4+ counts < 150 x 106/L).

Studies have shown that oral Zovirax reduced mortality in patients with advanced HIV disease. In addition, oral Zovirax provided effective prophylaxis for herpes virus disease. No significant effect was seen on the prophylaxis of CMV disease or EBV disease.

Contraindications

Zovirax Tablets are contraindicated in patients known to be hypersensitive to aciclovir or valaciclovir.

Precautions

Use in patients with renal impairment and in elderly patients.

Aciclovir is eliminated by renal clearance, therefore the dose must be reduced in patients with renal impairment (see Dosage and Administration). Elderly patients are likely to have reduced renal function and therefore the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see Adverse Effects). The dosage should be adjusted in patients with renal impairment, see Dosage and Administration.

Hydration status.

Care should be taken to maintain adequate hydration in patients receiving high oral doses of aciclovir.
Resistant strains have been isolated in vitro and in animals following treatment with aciclovir. HSV strains resistant in vitro to aciclovir have also been isolated from immunocompromised as well as immunocompetent patients receiving aciclovir for herpes simplex infections. Therefore, the potential for the development of resistant HSV strains in patients treated with aciclovir should be borne in mind. The relationship between the level of in vitro sensitivity of herpes viruses to aciclovir and clinical response to therapy has not been adequately established.
As aciclovir has been associated with reversible encephalopathic changes, it should be used with caution in patients with underlying neurological abnormalities, significant hypoxia or serious renal, hepatic or electrolyte abnormalities. It should also be used with caution in patients who have manifested neurological reactions to cytotoxic drugs or are receiving concomitantly interferon or intrathecal methotrexate.
Animal studies indicate that at high doses aciclovir is cytotoxic.

Use in pregnancy.

(Category B3)
Animal studies show that aciclovir crosses the placenta readily. Aciclovir was not teratogenic in the mouse (450 mg/kg/day p.o.), rabbit (50 mg/kg/day sc and iv) or rat (50 mg/kg/day sc) when dosed throughout the period of major organogenesis. This exposure in the rat resulted in plasma levels 11-fold the mean steady state peak concentration in human doses of 800 mg every 4 hours. In additional studies in which rats were given 3 sc doses of aciclovir 100 mg/kg on gestation day 10, fetal abnormalities, such as head and tail anomalies, were reported (exposure was 63-fold human levels after 800 mg every four hours).
There have been no adequate and well controlled studies concerning the safety of aciclovir in pregnant women. It should not be used during pregnancy unless the benefits to the patient clearly outweigh the potential risks to the fetus. If suppressive therapy is used in the perinatal period, it should not be assumed that viral shedding has ceased, or that the risk to fetus/ neonate has decreased. Pregnancy should be managed according to considerations normally applicable to patients with genital herpes.

Use in lactation.

Limited human data show that aciclovir does pass into breast milk. Aciclovir should only be administered to nursing mothers if the benefits to the mother outweigh the potential risks to the baby. Caution is therefore advised if aciclovir is to be administered to a nursing woman.

Paediatric use.

Safety and effectiveness in children have not been established.

Mutagenic potential.

Aciclovir was clastogenic in Chinese hamster cells in vivo, at exposure levels also causing nephrotoxicity (500 and 1000 mg/kg parenteral dose). There was also an increase, though not statistically significant, in chromosomal damage at maximum tolerated doses (100 mg/kg) of aciclovir in rats. No activity was found in a dominant lethal study in mice) or in 4 microbial assays. Positive results were obtained in 2 of 7 genetic toxicity assays using mammalian cells in vitro (positive in human lymphocytes in vitro and one locus in mouse lymphoma cells, negative at 2 other loci in mouse lymphoma cells and 3 loci in a Chinese hamster ovary cell line).
The results of these mutagenicity tests in vitro and in vivo suggest that aciclovir is unlikely to pose a genetic threat to man at therapeutic dose levels.

Carcinogenic potential.

Aciclovir was positive in one of two mouse cell transformation systems in vitro. Inoculation of the transformed cells into immune suppressed mice resulted in tumours. These data are suggestive of an oncogenic potential. However, the validity of this type of study is unclear. Lifetime oral dosing studies in mice and rats gave no evidence of tumourogenicity but in these species the absorption of oral aciclovir is poor and possibly self limiting.

Effects on fertility.

There is no information on the effect of Zovirax on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1 g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

Effects on ability to drive and use machines.

The clinical status of the patient and the adverse event profile of Zovirax should be borne in mind when considering the patient's ability to drive or operate machinery. There have been no studies to investigate the effect of Zovirax on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.

Interactions

Aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase aciclovir plasma concentrations. Probenecid and cimetidine increase the AUC of aciclovir by this mechanism and reduce aciclovir renal clearance. However, no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.
In patients receiving Zovirax, caution is required during concurrent administration with drugs which compete with aciclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites. Increase in plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplants, have been shown when the drugs are coadministered. However, no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.
In patients over 60 years of age, concurrent use of diuretics increases plasma levels of aciclovir very significantly. It is not known whether a similar effect occurs in young adults. In patients receiving Retrovir (zidovudine) no significant overall increase in toxicity was associated with the addition of Zovirax. No data are available on interactions between aciclovir and other antiretroviral therapies.

Adverse Effects

Zovirax tablets appear to be generally very well tolerated. Adverse effects are usually mild. However, the following have been noted.

Short-term administration for treatment for genital herpes.

Nausea and/or vomiting and headache were the most frequent adverse effects. Less frequent (< 1%) reactions included diarrhoea, dizziness, anorexia, fatigue, oedema, skin rashes, leg pain, inguinal adenopathy, medication taste and sore throat. Occasional changes in liver enzymes and changes in haematological parameters were also noted.

Long-term suppressive therapy for genital herpes.

Nausea and/or vomiting, headache, diarrhoea, vertigo and arthralgia were the most frequent adverse effects. Less frequent adverse effects included skin rash, insomnia, fatigue, fever, palpitation, sore throat, superficial thrombophlebitis, muscle cramps, pars planitis, menstrual abnormalities, lymphadenopathy, irritability, accelerated hair loss, depression and occasional increases in liver enzymes.

Treatment of herpes zoster.

The most commonly reported adverse effect in clinical trials was gastrointestinal disturbance. Other reports included aching, chest pain, confusion, constipation, diarrhoea, giddiness, hallucinations, headache, insomnia, nausea, rash, shaking, taste disturbance, tremor, vertigo and malaise, vomiting and mental status alteration. Significantly, the overall incidence of side effects reported was the same in patients on placebo.

Patients with advanced symptomatic HIV disease.

In patients receiving antiretroviral therapy (mainly oral Retrovir (zidovudine)), no significant overall increase in toxicity was associated with the addition of Zovirax. However, moderate increases in anaemia and neutropenia were seen in some studies in patients with advanced HIV disease.
The frequency categories associated with the adverse events below are estimates. For most events, suitable data for estimating incidence were not available. In addition, adverse events may vary in their incidence depending on the indication.
The following convention has been used for the classification of undesirable effects in terms of frequency: very common ≥ 1/10, common ≥ 1/100 and < 1/10, uncommon ≥ 1/1000 and < 1/100, rare ≥ 1/10,000 and < 1/1000, very rare < 1/10,000.

Blood and lymphatic system disorders.

Very rare: anaemia, leukopenia, thrombocytopenia.

Immune system disorders.

Rare: anaphylaxis.

Psychiatric and nervous system disorders.

Common: headache, dizziness, confusion, hallucinations, somnolence, convulsions.
Very rare: agitation, tremor, ataxia, dysarthria, psychotic symptoms, encephalopathy, coma.
The above events are reversible and usually reported in patients with renal impairment in whom the dosage was in excess of that recommended, or with other predisposing factors.

Respiratory, thoracic and mediastinal disorders.

Rare: dyspnoea.

Gastrointestinal disorders.

Common: nausea, vomiting, diarrhoea, abdominal pains.

Hepatobiliary disorders.

Rare: reversible rises in bilirubin and liver related enzymes.
Very rare: hepatitis, jaundice.

Skin and subcutaneous tissue disorders.

Common: pruritus, rashes (including photosensitivity).
Uncommon: urticaria, accelerated diffuse hair loss.
Accelerated diffuse hair loss has been associated with a wide variety of disease processes and medicines; the relationship of the event to aciclovir therapy is uncertain.
Rare: angioedema.

Renal and urinary disorders.

Rare: increases in blood urea and creatinine.
Very rare: acute renal failure, renal pain.
Renal pain may be associated with renal failure.

General disorders and administration site conditions.

Common: fatigue, fever.

Dosage and Administration

Zovirax Dispersible Tablets may be dispersed in a minimum of 50 mL of water, or swallowed whole with a little water.

Treatment of initial genital herpes.

One 200 mg tablet every 4 hours, while awake, for a total of 5 tablets daily for 10 days (total 50 tablets).

Chronic suppressive therapy for recurrent genital herpes.

One 200 mg tablet 3 times daily for up to 6 months. Many patients will, however, respond satisfactorily to one 200 mg tablet twice daily. Occasional breakthroughs have been reported in patients receiving 2, 3, 4 or 5 tablets daily. Suppressive therapy is not indicated for all patients with recurrent genital herpes (see Indications). Therapy should be discontinued at the end of 6 months to ascertain whether any change has occurred in the natural course of the disease in the particular patient.

Intermittent therapy for recurrent genital herpes in certain patients (see Indications).

One 200 mg tablet every 4 hours, while awake, for a total of 5 tablets daily for 5 days (total 25 tablets). Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.

Treatment of herpes zoster in adults.

800 mg 5 times daily at approximately four hourly intervals, omitting the night time dose. Therapy should commence as early as possible after the onset of rash but definitely within 72 hours of the appearance of the rash. Treatment should be continued for 7 days. For herpes zoster ophthalmicus, the recommended duration of therapy is 7 to 10 days. Attention should be given to maintaining adequate hydration in elderly patients.

Management of patients with advanced symptomatic HIV disease.

800 mg four times daily at approximately six hourly intervals. The duration of treatment in the controlled trials was 12 months. Oral Zovirax was given in conjunction with oral Retrovir (zidovudine) in most studies, at a range of doses. In a high percentage of the patients in the controlled trials, an initial zidovudine dose of 2 g daily followed after 4 weeks by 1 g daily was used. These doses are above the currently recommended dose of 600 mg daily. The safety and effectiveness of oral Zovirax taken in conjunction with other antiretroviral therapies could not be assessed.

Patients with acute or chronic renal impairment.

No data are currently available on the kinetics of oral aciclovir in patients with impaired renal function. However, based on studies with intravenous aciclovir infusion and theoretical considerations, the following dosage adjustments are recommended.

Genital herpes.

For patients with creatinine clearance < 10 mL/minute/1.73 m2, a 200 mg dose every 12 hours is recommended.

Herpes zoster, and in the management of patients with advanced symptomatic HIV disease.

For patients with creatinine clearance in the range 10-25 mL/minute/1.73 m2, it is recommended to adjust the dosage to 800 mg three times daily (approximately every 8 hours). For patients with creatinine clearance < 10 mL/minute/1.73 m2, 800 mg twice daily (approximately every 12 hours).

Dosage in the elderly.

The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see above). Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Overdosage

Symptoms and signs.

Aciclovir is only partly absorbed in the gastrointestinal tract. Patients have ingested overdoses of up to 20 g aciclovir on a single occasion, usually without toxic effects. Accidental, repeated overdoses of oral aciclovir over several days have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).
Overdosage of intravenous aciclovir has resulted in elevations of serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with intravenous overdosage.

Management.

Patients should be observed closely for signs of toxicity. Adequate hydration is essential to reduce the possibility of crystal formation in urine. Haemodialysis significantly enhances the removal of aciclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.
Contact the Poisons Information Centre (telephone 131 126) for advice on overdose management.

Presentation

Dispersible tablets (white, film coated, plain on reverse), 200 mg (round, biconvex, marked GXCF3): 25's*, 90's (bottle*, blister pack); 400 mg* (shield shaped, concave, marked GXCF5): 70's, 100's (bottle, blister pack); 800 mg* (oval, biconvex, marked GXCG1): 5's, 35's, 120's (bottle, blister pack).
Tablets* (white, plain on reverse), 200 mg (round, biconvex, marked GXCL3): 25's, 50's, 90's (blister pack), 90's (bottle); 400 mg (shield shaped, marked GXCM1): 70's, 100's (bottle, blister pack); 800 mg (elongated, biconvex, marked GXCX5): 5's, 35's, 120's (bottle, blister pack).
*Not currently marketed in Australia.

Storage

Zovirax Dispersible Tablets 200 mg, 400 mg and 800 mg.

Store below 30°C. Keep dry. Protect from light.

Zovirax Tablets 200 mg, 400 mg and 800 mg.

Store below 30°C and in a dry place.

Poison Schedule

S4.